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Study Exploring Safety, Pharmacokinetic and Pharmacodynamic of BN82451 in Male Huntington's Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02231580
Recruitment Status : Terminated (The study was terminated due to subject recruitment problems.)
First Posted : September 4, 2014
Results First Posted : January 29, 2018
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Huntington's Disease
Interventions Drug: BN82451B
Drug: Placebo
Enrollment 17
Recruitment Details The study was a double blind, placebo controlled, randomised, sequential dose ranging repeated dose trial where patients were recruited to a single study centre in Germany. It was planned to enrol 30 patients (10 in each of 3 cohorts). Patients were enrolled to the study from 1 September 2014 until early termination of the study on 31 March 2016.
Pre-assignment Details Male patients 20-70 years with a documented diagnosis of Huntington's Disease (HD) with at least 36 cytosine adenine guanine repeats in the Huntington gene were screened. Eligibile patients needed to meet defined criteria during quantitative motor function assessments. 25 patients were screened, 17 were enrolled and randomised to treatment.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Period Title: Overall Study
Started 14 3
Cohort 1 8 2
Cohort 2 6 1
Completed 9 3
Not Completed 5 0
Reason Not Completed
Adverse Event             5             0
Arm/Group Title BN82451B Placebo Total Title
Hide Arm/Group Description

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

[Not Specified]
Overall Number of Baseline Participants 14 3 17
Hide Baseline Analysis Population Description
Baseline characteristics are presented for the Safety Population, consisting of all randomised patients who received at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 3 participants 17 participants
46.6  (14.4) 50.0  (8.7) 46.6  (14.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 3 participants 17 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
14
 100.0%
3
 100.0%
17
 100.0%
1.Primary Outcome
Title Numbers of Patients Experiencing Treatment Emergent Adverse Events (TEAEs).
Hide Description The safety and tolerability of BN82451B versus placebo was determined after oral administration b.i.d. for 28 days in patients with HD. Numbers of patients experiencing TEAEs, including information on seriousness, intensity, drug relationship and those leading to withdrawal are presented for all doses of BN82451B and placebo.
Time Frame From Day 1 to end of study (a period of up to 7 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population consisted of all randomised patients who received at least one dose of study medication.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 14 3
Measure Type: Number
Unit of Measure: Participants
Patients with any TEAEs 11 2
Patients with any serious TEAE 0 0
Patients with at least 1 severe TEAE 0 0
Patients with at least 1 moderate TEAE 8 1
Patients with at least 1 mild TEAE 11 1
Patients with TEAEs related to study medication 9 0
Patients with TEAEs leading to withdrawal 5 0
Patients with any TEAEs leading to death 0 0
2.Secondary Outcome
Title Area Under the Plasma Concentration Time Curve (AUC)
Hide Description The AUC was determined for BN82451B and its metabolites BN2468 and BN7167 within a dosage interval (0-12 hours) on Days 1, and 14 and 28. Day 1 data represent the AUC after the first dose (AUC[0-12]). The data for Days 14 and 28 (AUC[τ,ss]) represent the AUC at steady state at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.
Time Frame 0-12 hours on Days 1, 14 and 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population consisted of all subjects from the safety population who had no major protocol deviations affecting the PK variables and who had a sufficient number of plasma BN82451B concentrations to estimate the main PK parameters.
Arm/Group Title BN82451B Cohort 1 BN82451B Cohort 2
Hide Arm/Group Description:
Patients randomised to receive BN82451B in cohort 1 received doses ranging from 40 to 60 mg BN82451B orally b.i.d. for up to 28 days.
Patients randomised to receive BN82451B in cohort 2 received doses ranging from 60 to 80 mg BN82451B orally b.i.d. for up to 28 days.
Overall Number of Participants Analyzed 8 6
Mean (Standard Deviation)
Unit of Measure: hours*nanograms per millilitre (h*ng/mL)
Day 1 BN82451B AUC(0-12) Number Analyzed 8 participants 6 participants
512.93  (112.53) 783.78  (144.45)
Day 1 BN2468 AUC(0-12) Number Analyzed 8 participants 0 participants
90.66  (40.68)
Day 1 BN7167 AUC(0-12) Number Analyzed 8 participants 6 participants
16.82  (9.01) 31.67  (24.63)
Day 14 BN82451B AUCτ,ss Number Analyzed 8 participants 6 participants
1521.11  (593.22) 2594.05  (1077.08)
Day 14 BN2468 AUC(τ,ss) Number Analyzed 8 participants 6 participants
735.51  (203.91) 1531.00  (412.43)
Day 14 BN7167 AUC(τ,ss) Number Analyzed 8 participants 6 participants
33.39  (20.08) 46.73  (36.76)
Day 28 BN82451B AUC(τ,ss) Number Analyzed 8 participants 6 participants
2357.95  (977.74) 3313.45  (1517.6)
Day 28 BN2468 AUC(τ,ss) Number Analyzed 8 participants 6 participants
1509.67  (105.94) 1936.35  (569.97)
Day 28 BN7167 AUC(τ,ss) Number Analyzed 8 participants 6 participants
34.64  (16.05) 63.81  (57.70)
3.Secondary Outcome
Title Peak Plasma Concentration (Cmax)
Hide Description Cmax was determined for BN82451B and its metabolites BN2468 and BN7167 on Days 1, 14 and 28. Day 1 data represent the PK after the first dose (Cmax). The data for Days 14 and 28 represent the Cmax at steady state (Cmax,ss) at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.
Time Frame Days 1, 14 and 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population consisted of all subjects from the safety population who had no major protocol deviations affecting the PK variables and who had a sufficient number of plasma BN82451B concentrations to estimate the main PK parameters.
Arm/Group Title BN82451B Cohort 1 BN82451B Cohort 2
Hide Arm/Group Description:
Patients randomised to receive BN82451B in cohort 1 received doses ranging from 40 to 60 mg BN82451B orally b.i.d. for up to 28 days.
Patients randomised to receive BN82451B in cohort 2 received doses ranging from 60 to 80 mg BN82451B orally b.i.d. for up to 28 days.
Overall Number of Participants Analyzed 8 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 BN82451B Cmax 71.61  (14.81) 101.45  (16.25)
Day 1 BN2468 Cmax 9.03  (4.14) 18.87  (13.00)
Day 1 BN7167 Cmax 3.62  (1.62) 5.61  (3.62)
Day 14 BN82451B Cmax,ss 162.88  (56.31) 271.64  (99.90)
Day 14 BN2468 Cmax,ss 75.34  (15.16) 125.34  (38.13)
Day 14 BN7167 Cmax,ss 4.90  (2.35) 6.28  (3.55)
Day 28 BN82451B Cmax,ss 251.77  (105.64) 340.41  (156.61)
Day 28 BN2468 Cmax,ss 135.19  (5.06) 171.64  (47.64)
Day 28 BN 7167 Cmax,ss 5.51  (1.82) 9.54  (6.92)
4.Secondary Outcome
Title Time to Peak Plasma Concentration (Tmax)
Hide Description Tmax is the empirical time of Cmax and was determined for BN82451B and its metabolites BN2468 and BN7167 on Days 1, 14 and 28. Day 1 data represent the PK after the first dose (Tmax). The data for Days 14 and 28 represent the Tmax at steady state (Tmax,ss) at the initial cohort dose and following dose escalation, respectively. Data is presented for cohorts 1 and 2, as the study terminated prior to dosing of cohort 3.
Time Frame Days 1, 14 and 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population consisted of all subjects from the safety population who had no major protocol deviations affecting the PK variables and who had a sufficient number of plasma BN82451B concentrations to estimate the main PK parameters.
Arm/Group Title BN82451B Cohort 1 BN82451B Cohort 2
Hide Arm/Group Description:
Patients randomised to receive BN82451B in cohort 1 received doses ranging from 40 to 60 mg BN82451B orally b.i.d. for up to 28 days.
Patients randomised to receive BN82451B in cohort 2 received doses ranging from 60 to 80 mg BN82451B orally b.i.d. for up to 28 days.
Overall Number of Participants Analyzed 8 6
Median (Full Range)
Unit of Measure: hours
Day 1 BN82451B Tmax
3.0
(2.0 to 3.0)
2.51
(2.0 to 3.0)
Day 1 BN2468 Tmax
9.98
(1.0 to 12.02)
11.92
(11.92 to 11.92)
Day 1 BN7167 Tmax
1.00
(1.00 to 2.00)
1.00
(1.00 to 2.00)
Day 14 BN82451B Tmax,ss
3.0
(2.0 to 4.0)
3.0
(2.0 to 3.5)
Day 14 BN2468 Tmax,ss
4
(1.05 to 8)
2.51
(1 to 8)
Day 14 BN7167 Tmax,ss
1
(1 to 2.13)
1
(1 to 2)
Day 28 BN82451B Tmax,ss
3
(2.02 to 4)
2.56
(2 to 3.02)
Day 28 BN2468 Tmax,ss
4.06
(2 to 6)
2.06
(1 to 12)
Day 28 BN7167 Tmax,ss
1
(0.55 to 2)
1.52
(1 to 2)
5.Secondary Outcome
Title Change From Baseline to Day 28 in the Position-index as Determined by Choreomotography
Hide Description Choreatic (involuntary) movements were assessed using Choreomotography by calculating a position-index and orientation-index. Patients were asked to grasp and lift a device equipped with an electromagnetic sensor, and were asked to hold the device as stable as possible. Three dimensional (3D) changes in position (x, y and z) and orientation (roll, pitch and yaw) were recorded and used to calculate a position-index and an orientation-index. This method provided an objective measure of the involuntary movements. 5 trials of 20 seconds duration were performed with each hand, and the start and end of each trial was signalled by a cueing tone. The mean changes from Baseline to Day 28 in the position-index of the right and left hands are presented as raw data. The statistical analyses present geometric least squares (GLS) mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacodynamic (PD) population consisted of all subjects from the safety population who have not reported major protocol violations impacting quantitative measures of motor function (Q-motor) evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: metres per second (m/s)
Left hand position-index 0.021  (0.024) 0.009  (0.007)
Right hand position-index 0.018  (0.014) 0.009  (0.006)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand position-index statistical analysis is presented (BN82451B versus Placebo). The Mixed Effect Model Repeat Measurement (MMRM) analysis was performed on log-transformed data using the restricted maximum likelihood (REML) model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5743
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.104
Confidence Interval (2-Sided) 90%
0.823 to 1.482
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand position-index statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.4349
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.141
Confidence Interval (2-Sided) 90%
0.862 to 1.510
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline to Day 28 in the Orientation-index as Determined by Choreomotography
Hide Description Choreatic (involuntary) movements were assessed using Choreomotography by calculating a position-index and orientation-index. Patients were asked to grasp and lift a device equipped with an electromagnetic sensor, and were asked to hold the device as stable as possible. 3D changes in position (x, y and z) and orientation (roll, pitch and yaw) were recorded and used to calculate a position-index and an orientation-index. This method provided an objective measure of the involuntary movements. 5 trials of 20 seconds duration were performed with each hand, and the start and end of each trial was signalled by a cueing tone. The mean changes from Baseline to Day 28 in the orientation-index of the right and left hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: radians per second (radians/s)
Left hand orientation-index 0.131  (0.125) 0.082  (0.100)
Right hand orientation-index 0.098  (0.087) 0.054  (0.045)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand orientation-index statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8937
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.035
Confidence Interval (2-Sided) 90%
0.675 to 1.587
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand orientation-index statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6360
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.093
Confidence Interval (2-Sided) 90%
0.800 to 1.493
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Grip Force Variability as Determined by Manumotography
Hide Description The coordination of isometric grip forces in the precision grip between the thumb and index finger were assessed by Manumotography. Grip forces were assessed during grip initiation, object transport and in a static holding phase. Subjects were instructed to grasp and lift a device equipped with a force transducer and 3D position sensor in the precision grip between thumb and index finger and hold it stable adjacent to a marker 10 centimetres high. Grip forces and 3D position and orientation of the object were recorded. Mean isometric grip forces and grip force variability in the static phase (expressed as coefficient of variation = standard deviation/mean x 100 [GFV-C]) were calculated during a 15 second period. 5 trials of 20 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the grip force variability of each hand are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: percentage of variation
Left hand grip force variability 5.74  (4.38) 2.61  (4.57)
Right hand grip force variability 5.82  (7.94) 2.35  (1.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand grip force variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2865
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.247
Confidence Interval (2-Sided) 90%
0.886 to 1.756
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand grip force variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5338
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.160
Confidence Interval (2-Sided) 90%
0.781 to 1.724
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Isometric Grip Forces as Determined by Manumotography
Hide Description The coordination of isometric grip forces in the precision grip between the thumb and index finger were assessed by Manumotography. Grip forces were assessed during grip initiation, object transport and in a static holding phase. Subjects were instructed to grasp and lift a device equipped with a force transducer and 3D position sensor in the precision grip between thumb and index finger and hold it stable adjacent to a marker 10 centimetres high. Grip forces and 3D position and orientation of the object were recorded. Mean isometric grip forces and grip force variability in the static phase (expressed as coefficient of variation = standard deviation/mean x 100 [GFV-C]) were calculated during a 15 second period. 5 trials of 20 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the mean isometric grip forces of each hand are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: Newton
Left hand isometric grip forces -0.75  (2.86) 1.55  (1.99)
Right hand isometric grip forces -2.06  (6.00) 0.91  (1.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand isometric grip forces statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0864
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.693
Confidence Interval (2-Sided) 90%
0.487 to 0.985
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand isometric grip forces statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0399
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.686
Confidence Interval (2-Sided) 90%
0.508 to 0.925
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Onset Intervals (IOI) as Assessed by Digitomotography
Hide Description Digitomotography was used to assess the duration and the variability of tap IOI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left finger IOI variability 0.039  (0.048) -0.009  (0.002)
Right finger IOI variability 0.057  (0.062) 0.038  (0.049)
Left finger IOI duration 0.088  (0.075) -0.015  (0.041)
Right finger IOI duration 0.069  (0.059) 0.032  (0.031)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger IOI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0574
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.509
Confidence Interval (2-Sided) 90%
1.060 to 2.150
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger IOI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8277
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.953
Confidence Interval (2-Sided) 90%
0.662 to 1.372
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger IOI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0162
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.238
Confidence Interval (2-Sided) 90%
1.074 to 1.426
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger IOI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6320
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.038
Confidence Interval (2-Sided) 90%
0.912 to 1.182
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of Tap Durations (TD) as Assessed by Digitomotography
Hide Description Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right hands are presented a raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left finger Variability of TD 0.007  (0.024) -0.007  (0.015)
Right finger Variability of TD 0.017  (0.016) 0.012  (0.017)
Left finger Duration of TD 0.010  (0.021) -0.011  (0.039)
Right finger Duration of TD 0.012  (0.021) 0.001  (0.025)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger variability of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3005
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.308
Confidence Interval (2-Sided) 90%
0.85 to 2.014
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger variability of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.4793
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.177
Confidence Interval (2-Sided) 90%
0.804 to 1.722
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger duration of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2653
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.150
Confidence Interval (2-Sided) 90%
0.934 to 1.416
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger duration of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6777
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.045
Confidence Interval (2-Sided) 90%
0.875 to 1.248
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Peak Intervals (IPI) as Assessed by Digitomotography
Hide Description Digitomotography was used to assess the duration and the variability of tap IPI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left finger IPI variability 0.040  (0.049) -0.009  (0.007)
Right finger IPI variability 0.057  (0.067) 0.038  (0.044)
Left finger IPI duration 0.088  (0.076) -0.017  (0.042)
Right finger IPI duration 0.069  (0.059) 0.031  (0.030)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger IPI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0326
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.618
Confidence Interval (2-Sided) 90%
1.124 to 2.331
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger IPI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6016
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.886
Confidence Interval (2-Sided) 90%
0.605 to 1.299
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger IPI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0152
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.242
Confidence Interval (2-Sided) 90%
1.077 to 1.433
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger IPI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6033
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.042
Confidence Interval (2-Sided) 90%
0.915 to 1.186
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of Inter Tap Intervals (ITI) as Assessed by Digitomotography
Hide Description Digitomotography was used to assess the duration and the variability of ITI in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left finger ITI Variability 0.041  (0.05) -0.007  (0.01)
Right finger ITI Variability 0.053  (0.068) 0.03  (0.034)
Left finger ITI Duration 0.078  (0.076) -0.005  (0.006)
Right finger ITI Duration 0.056  (0.048) 0.03  (0.046)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger ITI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0520
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.657
Confidence Interval (2-Sided) 90%
1.086 to 2.529
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger ITI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6978
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.916
Confidence Interval (2-Sided) 90%
0.630 to 1.333
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger ITI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0522
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.298
Confidence Interval (2-Sided) 90%
1.043 to 1.614
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger ITI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.9012
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.014
Confidence Interval (2-Sided) 90%
0.837 to 1.229
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Variability of Peak Tapping Forces (TF) as Assessed by Digitomotography
Hide Description Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the variability of TF for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: percentage of variation
Left finger TF 0.65  (6.97) -6.43  (6.26)
Right finger TF 3.75  (12.86) -0.11  (8.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger TF statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1779
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.198
Confidence Interval (2-Sided) 90%
0.96 to 1.494
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger TF statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8036
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.966
Confidence Interval (2-Sided) 90%
0.765 to 1.220
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Tapping Frequency (Freq) as Assessed by Digitomotography
Hide Description Digitomotography was used to assess the duration and the variability of TD in an index finger speeded tapping task. The patient placed their hand on a hand rest with their index finger positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to finger tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: Hertz
Left finger freq -0.492  (0.382) -0.001  (0.315)
Right finger freq -0.466  (0.389) -0.365  (0.231)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left finger freq statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0177
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.812
Confidence Interval (2-Sided) 90%
0.706 to 0.935
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right finger freq statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6491
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.967
Confidence Interval (2-Sided) 90%
0.856 to 1.093
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Dysdiadochomotography
Hide Description Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left hand IOI variability 0.032  (0.135) 0.036  (0.023)
Right hand IOI variability 0.031  (0.094) 0.163  (0.276)
Left hand IOI duration 0.054  (0.114) 0.028  (0.043)
Right hand IOI duration 0.074  (0.101) 0.074  (0.132)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand IOI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6176
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.168
Confidence Interval (2-Sided) 90%
0.697 to 1.955
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand IOI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.4541
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.759
Confidence Interval (2-Sided) 90%
0.411 to 1.399
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand IOI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2018
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.119
Confidence Interval (2-Sided) 90%
0.967 to 1.294
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand IOI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6527
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.046
Confidence Interval (2-Sided) 90%
0.886 to 1.234
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Dysdiadochomotography
Hide Description Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left hand variability of TD 0.001  (0.138) 0.023  (0.026)
Right hand variability of TD -0.012  (0.073) 0.078  (0.128)
Left hand duration of TD -0.006  (0.088) 0.017  (0.027)
Right hand duration of TD -0.019  (0.089) 0.022  (0.069)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand variability of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8279
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.929
Confidence Interval (2-Sided) 90%
0.529 to 1.630
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand variability of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2738
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.612
Confidence Interval (2-Sided) 90%
0.292 to 1.283
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand duration of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.9218
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.018
Confidence Interval (2-Sided) 90%
0.752 to 1.378
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand duration of TD statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5032
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.847
Confidence Interval (2-Sided) 90%
0.561 to 1.277
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Dysdiadochomotography
Hide Description Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left hand IPI variability 0.045  (0.124) 0.049  (0.046)
Right hand IPI variability 0.027  (0.07) 0.131  (0.219)
Left hand IPI duration 0.057  (0.109) 0.029  (0.04)
Right hand IPI duration 0.079  (0.105) 0.066  (0.118)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand IPI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6759
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.140
Confidence Interval (2-Sided) 90%
0.677 to 1.917
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand IPI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5764
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.815
Confidence Interval (2-Sided) 90%
0.444 to 1.496
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand IPI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2127
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.115
Confidence Interval (2-Sided) 90%
0.965 to 1.289
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand IPI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5661
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.059
Confidence Interval (2-Sided) 90%
0.897 to 1.25
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Dysdiadochomotography
Hide Description Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left hand ITI variability 0.036  (0.061) 0.015  (0.017)
Right hand ITI variability 0.053  (0.082) 0.017  (0.018)
Left hand ITI duration 0.064  (0.070) 0.006  (0.029)
Right hand ITI duration 0.094  (0.097) 0.022  (0.014)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand ITI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0874
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.571
Confidence Interval (2-Sided) 90%
1.018 to 2.424
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand ITI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.6431
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.18
Confidence Interval (2-Sided) 90%
0.644 to 2.162
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand ITI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0389
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.193
Confidence Interval (2-Sided) 90%
1.038 to 1.371
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand ITI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1641
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.138
Confidence Interval (2-Sided) 90%
0.976 to 1.327
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Dysdiadochomotography
Hide Description Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The mean changes from Baseline to Day 28 in the variability of TF for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: percentage of variation
Left hand TF variability 3.50  (7.44) 9.98  (2.22)
Right hand TF variability 2.5  (10.87) 3.61  (2.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand TF variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5668
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 90%
0.755 to 1.147
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand TF variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.8686
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.978
Confidence Interval (2-Sided) 90%
0.778 to 1.229
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Dysdiadochomotography
Hide Description Dysdiadochomotography was used to assess the regularity of hand taps performed when alternating between the palm and dorsal surface of the hand performing a repetitive pronation/supination movement. The force and duration of the hand taps were recorded, with their hand positioned on a force transducer, and recordings were started after practice runs. The patient was then instructed to hand tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each hand. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. GLS mean ratios are in original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 11 3
Mean (Standard Deviation)
Unit of Measure: Hertz
Left hand freq -0.185  (0.402) -0.073  (0.088)
Right hand freq -0.236  (0.349) -0.121  (0.189)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left hand freq statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1244
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.879
Confidence Interval (2-Sided) 90%
0.765 to 1.009
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right hand freq statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3535
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.919
Confidence Interval (2-Sided) 90%
0.789 to 1.069
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of IOI as Assessed by Pedomotography
Hide Description Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of IOI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 10 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left foot IOI variability Number Analyzed 9 participants 3 participants
0.146  (0.353) -0.1  (0.122)
Right foot IOI variability Number Analyzed 10 participants 3 participants
0.120  (0.177) 0.090  (0.15)
Left foot IOI duration Number Analyzed 9 participants 3 participants
0.109  (0.354) -0.123  (0.199)
Right foot IOI duration Number Analyzed 10 participants 3 participants
0.267  (0.461) 0.075  (0.164)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot IOI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.015
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 2.163
Confidence Interval (2-Sided) 90%
1.295 to 3.614
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot IOI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.5136
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.274
Confidence Interval (2-Sided) 90%
0.688 to 2.361
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot IOI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0218
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.560
Confidence Interval (2-Sided) 90%
1.139 to 2.137
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot IOI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3720
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.251
Confidence Interval (2-Sided) 90%
0.825 to 1.899
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of TD as Assessed by Pedomotography
Hide Description Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of TD for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 10 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left foot TD variability Number Analyzed 9 participants 3 participants
0.225  (0.332) -0.056  (0.058)
Right foot TD variability Number Analyzed 10 participants 3 participants
0.306  (0.566) 0.105  (0.140)
Left foot TD duration Number Analyzed 9 participants 3 participants
0.179  (0.28) -0.040  (0.106)
Right foot TD duration Number Analyzed 10 participants 3 participants
0.358  (0.609) 0.083  (0.133)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot TD variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.915
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.911
Confidence Interval (2-Sided) 90%
1.017 to 3.592
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot TD variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.2745
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.687
Confidence Interval (2-Sided) 90%
0.762 to 3.737
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot TD duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1148
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.598
Confidence Interval (2-Sided) 90%
0.980 to 2.608
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot TD duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3080
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.454
Confidence Interval (2-Sided) 90%
0.789 to 2.679
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of IPI as Assessed by Pedomotography
Hide Description Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of IPI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 10 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left foot IPI variability Number Analyzed 9 participants 3 participants
0.115  (0.248) -0.108  (0.131)
Right foot IPI variability Number Analyzed 10 participants 3 participants
0.117  (0.150) 0.098  (0.164)
Left foot IPI duration Number Analyzed 9 participants 3 participants
0.117  (0.383) -0.123  (0.206)
Right foot IPI duration Number Analyzed 10 participants 3 participants
0.295  (0.469) 0.073  (0.158)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot IPI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0079
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 2.272
Confidence Interval (2-Sided) 90%
1.381 to 3.737
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot IPI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0204
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.210
Confidence Interval (2-Sided) 90%
0.686 to 2.133
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot IPI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0204
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.564
Confidence Interval (2-Sided) 90%
1.144 to 2.138
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot IPI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3144
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.269
Confidence Interval (2-Sided) 90%
0.856 to 1.884
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Duration and Variability of ITI as Assessed by Pedomotography
Hide Description Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the duration and variability of ITI for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day-1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 10 3
Mean (Standard Deviation)
Unit of Measure: seconds
Left foot ITI variability Number Analyzed 9 participants 3 participants
0.003  (0.203) -0.047  (0.108)
Right foot ITI variability Number Analyzed 10 participants 3 participants
0.023  (0.118) -0.016  (0.089)
Left foot ITI duration Number Analyzed 9 participants 3 participants
-0.049  (0.232) -0.076  (0.092)
Right foot ITI duration Number Analyzed 10 participants 3 participants
-0.016  (0.121) -0.012  (0.056)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot ITI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0324
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.914
Confidence Interval (2-Sided) 90%
1.167 to 3.141
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot ITI variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.246
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.462
Confidence Interval (2-Sided) 90%
0.85 to 2.515
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot ITI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1057
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.387
Confidence Interval (2-Sided) 90%
0.994 to 1.935
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot ITI duration statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.7342
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.074
Confidence Interval (2-Sided) 90%
0.758 to 1.523
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Variability of Peak TF as Assessed by Pedomotography
Hide Description Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The mean changes from Baseline to Day 28 in the variability of TF for the left and right feet are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 10 3
Mean (Standard Deviation)
Unit of Measure: percentage of variation
Left foot TF variability Number Analyzed 9 participants 3 participants
11.63  (16.38) -20.19  (34.30)
Right foot TF variability Number Analyzed 10 participants 3 participants
-2.52  (22.35) -18.31  (6.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot TF variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.1027
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.392
Confidence Interval (2-Sided) 90%
0.997 to 1.943
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot TF variability statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.4494
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 1.158
Confidence Interval (2-Sided) 90%
0.840 to 1.595
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline to Day 28 in the Mean Tapping Frequency as Assessed by Pedomotography
Hide Description Pedomotography was used to assess the tap duration and variability in a foot speeded tapping task. The patient placed their foot on the foot device such that the ball of the foot was positioned above a force transducer, and recordings were started after practice runs. The patient was then instructed to foot tap as fast as possible between 2 auditory cues. The beginning of a tap was defined as a rise of the force by 0.05 N above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. 5 trials of 10 seconds duration were performed with each foot. The tapping frequency was calculated as the number of taps between the onsets of the first and the last tap divided by the time in between. The mean changes from Baseline to Day 28 in the tapping frequency for the left and right hands are presented as raw data. The statistical analyses present GLS mean ratios in the original units.
Time Frame Baseline (Day -1) to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The PD population consisted of all subjects from the safety population who have not reported major protocol violations impacting Q-motor evaluation and who have a Q-motor evaluation assessed both at Baseline (Day -1) and at one post baseline visit.
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description:

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Overall Number of Participants Analyzed 10 3
Mean (Standard Deviation)
Unit of Measure: Hertz
Left foot freq Number Analyzed 9 participants 3 participants
-0.259  (0.513) 0.556  (0.678)
Right foot freq Number Analyzed 10 participants 3 participants
-0.383  (0.481) -0.18  (0.550)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Left foot freq statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0350
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.699
Confidence Interval (2-Sided) 90%
0.530 to 0.922
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BN82451B, Placebo
Comments Right foot freq statistical analysis is presented (BN82451B versus Placebo). The MMRM analysis was performed on log-transformed data using the REML model including fixed categorical effects of treatment/cohort group, visit and treatment/cohort by visit interaction as well as the continuous fixed covariate of baseline value. Cohort was fitted as random effect.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.3556
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter GLS mean ratio
Estimated Value 0.853
Confidence Interval (2-Sided) 90%
0.640 to 1.136
Estimation Comments [Not Specified]
Time Frame From Day 1 to the end of study visit (a period of up to 7 weeks, consisting of up to 28 days of treatment and up to 3 weeks follow up).
Adverse Event Reporting Description AE data is reported as TEAEs.
 
Arm/Group Title BN82451B Placebo
Hide Arm/Group Description

Patients were randomised to receive oral study medication, BN82451B, b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of BN82451B was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 milligrams (mg) b.i.d.

For cohort 1, 40 mg BN82451B b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg BN82451B b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg BN82451B b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

Patients were randomised to receive oral placebo b.i.d. from Day 1 to Day 27, under double-blinded conditions. On Day 28 only one morning dose of placebo was administered. It was planned for patients to be assigned to 3 cohorts to receive 3 dose levels ranging between 40 and 80 mg b.i.d.

For cohort 1, 40 mg placebo b.i.d. was administered during the first 14 days. If this dose was well tolerated then it was increased to 60 mg b.i.d. for 13 days and one morning dose of 60 mg on Day 28.

For cohort 2, 60 mg placebo b.i.d. was administered during the first 14 days. If 60 mg b.i.d was well tolerated then it was increased to 80 mg b.i.d. for 13 days and one morning dose of 80 mg on Day 28.

For cohort 3 it was planned to administer 80 mg placebo b.i.d for 27 days with one morning dose of 80 mg on Day 28. The study was terminated early before completion of cohort 2.

All-Cause Mortality
BN82451B Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
BN82451B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/14 (0.00%)      0/3 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
BN82451B Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/14 (78.57%)      2/3 (66.67%)    
Ear and labyrinth disorders     
Ear swelling  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Gastrointestinal disorders     
Vomiting  1  3/14 (21.43%)  4 0/3 (0.00%)  0
Diarrhoea  1  2/14 (14.29%)  2 0/3 (0.00%)  0
Nausea  1  2/14 (14.29%)  3 0/3 (0.00%)  0
General disorders     
Fatigue  1  3/14 (21.43%)  3 0/3 (0.00%)  0
Face oedema  1  2/14 (14.29%)  3 0/3 (0.00%)  0
Inflammation  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Infections and infestations     
Impetigo  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Nasopharyngitis  1  0/14 (0.00%)  0 1/3 (33.33%)  1
Injury, poisoning and procedural complications     
Laceration  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Excoriation  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Investigations     
Gamma-glutamyltransferase increased  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  2/14 (14.29%)  2 0/3 (0.00%)  0
Neck pain  1  0/14 (0.00%)  0 1/3 (33.33%)  1
Nervous system disorders     
Headache  1  3/14 (21.43%)  4 0/3 (0.00%)  0
Dizziness  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Hypoaesthesia  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Depressed level of consciousness  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Presyncope  1  2/14 (14.29%)  2 0/3 (0.00%)  0
Dyskinesia  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  5/14 (35.71%)  5 0/3 (0.00%)  0
Acne  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Rash generalised  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Dry skin  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Hyperhidrosis  1  1/14 (7.14%)  1 0/3 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA19.0
The study was terminated prematurely due to subject recruitment problems before the completion of cohort 2.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI shall not proceed to publication or communication in connection with the subject matter of this Agreement or Results, without the prior written consent of Ipsen.
Results Point of Contact
Name/Title: Vice President Early Development & Clinical Pharmacology
Organization: Ipsen
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02231580     History of Changes
Other Study ID Numbers: 8-55-52966-005
2013-002899-41 ( EudraCT Number )
First Submitted: September 2, 2014
First Posted: September 4, 2014
Results First Submitted: April 10, 2017
Results First Posted: January 29, 2018
Last Update Posted: January 15, 2019