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Study Evaluating The Safety, Tolerability And Brain Function Of 2 Doses Of PF-0254920 In Subjects With Early Huntington's Disease

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: NCT01806896
Recruitment Status : Completed
First Posted : March 7, 2013
Results First Posted : December 14, 2017
Last Update Posted : December 14, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Huntington's Disease
Interventions Drug: PF-02545920
Drug: Placebo
Enrollment 37
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period. Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Period Title: Overall Study
Started 20 17
Received Treatment 19 17
Completed 17 17
Not Completed 3 0
Reason Not Completed
Adverse Event             2             0
Other             1             0
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day Total
Hide Arm/Group Description Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period. Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period. Total of all reporting groups
Overall Number of Baseline Participants 19 17 36
Hide Baseline Analysis Population Description
The baseline analysis population included all participants who were randomized and received at least 1 dose of PF-02545920 or placebo.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 17 participants 36 participants
47.4  (12.1) 43.1  (11.8) 45.4  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
Female
8
  42.1%
10
  58.8%
18
  50.0%
Male
11
  57.9%
7
  41.2%
18
  50.0%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of treatment and up to the follow-up period that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.
Time Frame Baseline up to Day 38
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
AEs 18 14
SAEs 1 1
2.Primary Outcome
Title Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern (Without Regard to Baseline Abnormality)
Hide Description The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total and direct bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine/serum pregnancy test, glycosylated hemoglobin [HbA1c, if diabetic]).
Time Frame Baseline up to Day 38
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
8 8
3.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Vital Signs Findings
Hide Description Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate less than (<)40 or greater than (>)120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of greater than or equal to (>=)30 millimeters of mercury (mmHg) change from baseline or SBP <90 mmHg, diastolic blood pressure (DBP) >=20 mmHg change from baseline or DBP <50 mmHg.
Time Frame Baseline up to Day 38
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
Supine SBP <90 mmHg 0 0
Standing SBP <90 mmHg 1 0
Supine DBP <50 mmHg 2 1
Standing DBP <50 mmHg 1 0
Supine Pulse Rate <40 or >120 bpm 0 0
Standing Pulse Rate <40 or >140 bpm 1 0
Increase From Baseline in Supine SBP >=30 mmHg 1 0
Increase From Baseline in Standing SBP >=30 mmHg 2 2
Increase From Baseline in Supine DBP >=20 mmHg 1 0
Increase From Baseline in Standing DBP >=20 mmHg 1 0
Decrease From Baseline in Supine SBP >=30 mmHg 1 0
Decrease From Baseline in Standing SBP >=30 mmHg 1 0
Decrease From Baseline in Supine DBP >=20 mmHg 2 1
Decrease From Baseline in Standing DBP >=20 mmHg 3 0
4.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
Hide Description ECG parameters included PR interval, QRS complex, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval ≥200 milliseconds (msec) or ≥25% increase when baseline is >100 msec; QRS interval ≥50% increase from baseline when baseline is less than or equal to (<=)200 msec; and QTcF ≥450 msec or ≥30 msec increase from baseline.
Time Frame Baseline up to Day 38
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
PR Interval >=200 msec 1 1
PR Interval >=300 msec 0 0
QTcF Interval 450-<480 msec 2 0
QTcF Interval 480-<500 msec 0 0
QTcF Interval >=500 msec 0 0
PR Interval >=25% increase when baseline >100 msec 0 0
PR Interval >=25% increase when baseline >200 msec 0 0
QRS >=50% increase when baseline <=100 msec 0 0
QRS >=50% increase when baseline <=200 msec 0 0
QTcF Interval Increase 30-<60 msec 1 0
QTcF Interval Increase >=60 msec 0 0
5.Primary Outcome
Title Number of Participants With Change From Baseline in Body Weight of >=7%
Hide Description Weight assessment was performed by a study physician or a trained study nurse and was included in the physical examination.
Time Frame Baseline up to Day 38
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
0 0
6.Primary Outcome
Title Categorical Summary of Participants Meeting Stopping Criteria
Hide Description Absolute neutrophil count (ANC) and WBC were monitored for safety. Participants with WBC <3000 but >=2000 cells/mm^3 or ANC <1500 but >=1000 cells/mm^3 were to have study treatment suspended. Participants with WBC <2000 or ANC <1000 cells/mm^3 were to be discontinued from study participation.
Time Frame Baseline up to Day 38
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
WBC 2000-3000 or ANC 1000-1500 cells/mm^3 0 1
WBC <2000 or ANC <1000 cells/mm^3 0 0
Discontinued/Suspended Due to WBC or ANC Findings 0 0
ANC<500 cells/mm^3 0 0
7.Primary Outcome
Title Change From Baseline in Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score at Day 28
Hide Description The UHDRS is a clinical rating scale to provide a uniform assessment of the clinical features and course of Huntington Disease. The Total Motor Score (TMS) is 1 of the 6 components of UHDRS, includes 31 items, and ranges from a scale of 0 to 124 (higher scores indicate more severe disease).
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and had taken at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Least Squares Mean (90% Confidence Interval)
Unit of Measure: units on a scale
0.19
(-1.73 to 2.12)
0.90
(-1.14 to 2.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Day 28)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments 2-sided p-value
Method ANCOVA
Comments Treatment differences are based on a mixed effect model including treatment as fixed effects and baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.71
Confidence Interval (2-Sided) 90%
-3.56 to 2.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.68
Estimation Comments [Not Specified]
8.Primary Outcome
Title Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Baseline
Hide Description C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.
Time Frame Baseline (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and had taken at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
Completed Suicide 0 0
Suicide Attempt 0 0
Acts Towards Imminent Suicidal Behavior 0 0
Suicidal Ideation 1 0
Self-Injurious Behavior, No Suicidal Intent 0 0
9.Primary Outcome
Title Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 7
Hide Description C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and had taken at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
Completed Suicide 0 0
Suicide Attempt 0 0
Acts Towards Imminent Suicidal Behavior 0 0
Suicidal Ideation 0 0
Self-Injurious Behavior, No Suicidal Intent 0 0
10.Primary Outcome
Title Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 28
Hide Description C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants randomized and had taken at least 1 dose of PF-02545920 or placebo.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
Completed Suicide 0 0
Suicide Attempt 0 0
Acts Towards Imminent Suicidal Behavior 0 0
Suicidal Ideation 2 0
Self-Injurious Behavior, No Suicidal Intent 0 0
11.Secondary Outcome
Title Change From Baseline in Functional Magnetic Resonance Imaging (fMRI) in Monetary Incentive Delay (MID) Task at Day 28
Hide Description The monetary incentive delay (MID) task is established as a reliable method to elicit ventral striatal (VS) activity in relation to reward/punishment anticipation and tracked with dysfunctionalities across a range of conditions in which incentive motivation is thought to be abnormal (schizophrenia, depression, substance abuse, and pathological gambling). Pharmacological intervention has demonstrated reversal of observed deficit. The beta contrast value of ’REW’ is for analysis of reward-related activity in VS within the task-related ’reward network’ during the gain condition (relative to neutral) of the MID task. The changes in beta contrasts (fMRI) provided are changes in parameter estimates and do not have a unit of measure.
Time Frame Baseline (Day 1), Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants randomized, who had taken at least 1 dose of PF-02545920 or placebo and who had valid data (thresholded by acceptable motion). n=number of participants analyzed in the respective arms. The per-protocol set (PPS) table was used, not the full analysis set (FAS) table.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 10 12
Least Squares Mean (90% Confidence Interval)
Unit of Measure: beta contrasts
Cue Rew>Neut Left VS
0.01
(-0.43 to 0.45)
0.11
(-0.29 to 0.50)
Cue Rew>Neut Right VS
-0.20
(-0.66 to 0.26)
-0.05
(-0.47 to 0.37)
Out_win_Rew>Out_win N Left VS
0.20
(-0.26 to 0.66)
0.45
(0.03 to 0.87)
Out_win_Rew>Out_win N Right VS
0.36
(-0.04 to 0.77)
0.89
(0.53 to 1.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Cue Rew>Neut Left VS)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments 2-sided p-value
Method ANCOVA
Comments Treatment differences are based on a mixed effect model including treatment as fixed effect and baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value -0.10
Confidence Interval (2-Sided) 90%
-0.72 to 0.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Cue Rew>Neut Right VS)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments 2-sided p-value
Method ANCOVA
Comments Treatment differences are based on a mixed effect model including treatment as fixed effect and baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value -0.15
Confidence Interval (2-Sided) 90%
-0.80 to 0.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Out_win_Rew>Out_win N Left VS)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments 2-sided p-value
Method ANCOVA
Comments Treatment differences are based on a mixed effect model including treatment as fixed effect and baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value -0.25
Confidence Interval (2-Sided) 90%
-0.89 to 0.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Out_win_Rew>Out_win N Right VS)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments 2-sided p-value
Method ANCOVA
Comments Treatment differences are based on a mixed effect model including treatment as fixed effect and baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value -0.53
Confidence Interval (2-Sided) 90%
-1.10 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Grip Strength Incentive Motivation Task at Day 28: Percent of Maximum Voluntary Contraction (MVC)
Hide Description This incentive force task was developed to independently dissociate the degree to which a participant responds to reward motivation versus emotional motivation. The task itself included 12 repetitions of 9 trial types, for a total of 108 trials, grouped in a single session lasting about 20 minutes. The trial types were generated according to a combination of 3 emotional categories (negative, neutral, and positive pictures presented) and to 3 monetary incentives (0.01, 0.1, and 1€). Emotional categories and monetary incentives were randomly distributed over the trials and the sequence was fixed such that all subjects were assessed on the exact same task. For each trial, the subject was first presented with an emotional picture displayed on screen for 3000 milliseconds (ms).
Time Frame Baseline, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants randomized, who had taken at least 1 dose of PF-02545920 or placebo and who had valid data (acceptable task engagement). n=number of participants analyzed in the respective arms. The PPS table was used, not the FAS table.
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description:
Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period.
Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
Overall Number of Participants Analyzed 16 17
Least Squares Mean (90% Confidence Interval)
Unit of Measure: percentage of MVC
Neutral Emotional Incentive Day 28
0.93
(-3.28 to 5.14)
-6.37
(-10.43 to -2.31)
Positive Emotional Incentive Day 28
1.10
(-3.10 to 5.31)
-6.47
(-10.53 to -2.40)
Negative Emotional Incentive Day 28
0.18
(-4.02 to 4.39)
-7.10
(-11.16 to -3.04)
0.01 Euro Monetary Incentive Day 28
-13.47
(-17.79 to -9.14)
-14.45
(-18.59 to -10.31)
0.1 Euro Monetary Incentive Day 28
-1.19
(-5.43 to 3.06)
-5.97
(-10.04 to -1.89)
1 Euro Monetary Incentive Day 28
16.85
(12.49 to 21.21)
0.50
(-3.78 to 4.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Emotional Incentive-Neutral) Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments 2-sided p-value
Method ANCOVA
Comments Mixed effect model including treatment, incentive and treatment*incentive as fixed effects; baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value 7.30
Confidence Interval (2-Sided) 90%
1.43 to 13.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.57
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Emotional Incentive-Positive) Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments 2-sided p-value
Method ANCOVA
Comments Mixed effect model including treatment, incentive and treatment*incentive as fixed effects; baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value 7.57
Confidence Interval (2-Sided) 90%
1.69 to 13.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.57
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Emotional Incentive-Negative) Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments 2-sided p-value
Method ANCOVA
Comments Mixed effect model including treatment, incentive and treatment*incentive as fixed effects; baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value 7.28
Confidence Interval (2-Sided) 90%
1.41 to 13.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.56
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Monetary Incentive-0.01 Euro) Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments 2-sided p-value
Method ANCOVA
Comments Mixed effect model including treatment, incentive and treatment*incentive as fixed effects; baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value 0.98
Confidence Interval (2-Sided) 90%
-4.91 to 6.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.58
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Monetary Incentive-0.1 Euro) Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments 2-sided p-value
Method ANCOVA
Comments Mixed effect model including treatment, incentive and treatment*incentive as fixed effects; baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value 4.78
Confidence Interval (2-Sided) 90%
-1.11 to 10.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.58
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection PF-02545920 20 mg Twice a Day, Placebo Twice a Day
Comments PF-02545920 versus Placebo (Monetary Incentive-1 Euro) Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments 2-sided p-value
Method ANCOVA
Comments Mixed effect model including treatment, incentive and treatment*incentive as fixed effects; baseline, age, gender and CAG repeats as covariates.
Method of Estimation Estimation Parameter Least square mean
Estimated Value 16.35
Confidence Interval (2-Sided) 90%
10.46 to 22.24
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.58
Estimation Comments [Not Specified]
Time Frame Baseline up to Day 38
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title PF-02545920 20 mg Twice a Day Placebo Twice a Day
Hide Arm/Group Description Participants received PF-02545920 orally every 12 hours according to a titration dosing scheme: 5 mg twice daily (BID) on Days 1-2, 10 mg BID on Days 3-4, 15 mg BID on Days 5-6, and 20 mg BID on Days 7-28; followed by a 7 to 10 day safety evaluation period. Participants received placebo matched to PF-02545920 orally every 12 hours for 28 days, followed by a 7 to 10 day safety evaluation period.
All-Cause Mortality
PF-02545920 20 mg Twice a Day Placebo Twice a Day
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PF-02545920 20 mg Twice a Day Placebo Twice a Day
Affected / at Risk (%) Affected / at Risk (%)
Total   1/19 (5.26%)   1/17 (5.88%) 
Nervous system disorders     
Chorea * 1  1/19 (5.26%)  0/17 (0.00%) 
Reproductive system and breast disorders     
Ovarian cyst * 1  0/19 (0.00%)  1/17 (5.88%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-02545920 20 mg Twice a Day Placebo Twice a Day
Affected / at Risk (%) Affected / at Risk (%)
Total   18/19 (94.74%)   14/17 (82.35%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/19 (0.00%)  1/17 (5.88%) 
Cardiac disorders     
Palpitations * 1  1/19 (5.26%)  0/17 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  0/19 (0.00%)  2/17 (11.76%) 
Gastrointestinal disorders     
Abdominal pain * 1  2/19 (10.53%)  0/17 (0.00%) 
Constipation * 1  1/19 (5.26%)  0/17 (0.00%) 
Diarrhoea * 1  3/19 (15.79%)  2/17 (11.76%) 
Dry mouth * 1  4/19 (21.05%)  1/17 (5.88%) 
Flatulence * 1  0/19 (0.00%)  1/17 (5.88%) 
Gastrointestinal disorder * 1  1/19 (5.26%)  0/17 (0.00%) 
Mouth ulceration * 1  0/19 (0.00%)  1/17 (5.88%) 
Nausea * 1  5/19 (26.32%)  2/17 (11.76%) 
Vomiting * 1  2/19 (10.53%)  0/17 (0.00%) 
General disorders     
Asthenia * 1  2/19 (10.53%)  1/17 (5.88%) 
Fatigue * 1  8/19 (42.11%)  4/17 (23.53%) 
Feeling hot * 1  1/19 (5.26%)  0/17 (0.00%) 
Gait disturbance * 1  0/19 (0.00%)  1/17 (5.88%) 
Thirst * 1  1/19 (5.26%)  1/17 (5.88%) 
Infections and infestations     
Nasopharyngitis * 1  1/19 (5.26%)  0/17 (0.00%) 
Pharyngitis * 1  1/19 (5.26%)  0/17 (0.00%) 
Rhinitis * 1  0/19 (0.00%)  1/17 (5.88%) 
Urinary tract infection * 1  0/19 (0.00%)  1/17 (5.88%) 
Investigations     
Blood pressure increased * 1  1/19 (5.26%)  0/17 (0.00%) 
Blood urine present * 1  1/19 (5.26%)  0/17 (0.00%) 
Electrocardiogram QRS complex prolonged * 1  0/19 (0.00%)  1/17 (5.88%) 
Electrocardiogram QT prolonged * 1  1/19 (5.26%)  1/17 (5.88%) 
Neutrophil count decreased * 1  0/19 (0.00%)  3/17 (17.65%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/19 (5.26%)  0/17 (0.00%) 
Glucose tolerance impaired * 1  0/19 (0.00%)  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/19 (5.26%)  0/17 (0.00%) 
Muscle spasms * 1  0/19 (0.00%)  1/17 (5.88%) 
Musculoskeletal pain * 1  1/19 (5.26%)  0/17 (0.00%) 
Pain in extremity * 1  0/19 (0.00%)  1/17 (5.88%) 
Nervous system disorders     
Akathisia * 1  2/19 (10.53%)  0/17 (0.00%) 
Chorea * 1  4/19 (21.05%)  0/17 (0.00%) 
Dysgeusia * 1  1/19 (5.26%)  0/17 (0.00%) 
Headache * 1  5/19 (26.32%)  6/17 (35.29%) 
Migraine * 1  1/19 (5.26%)  1/17 (5.88%) 
Oromandibular dystonia * 1  1/19 (5.26%)  0/17 (0.00%) 
Presyncope * 1  1/19 (5.26%)  0/17 (0.00%) 
Somnolence * 1  3/19 (15.79%)  0/17 (0.00%) 
Psychiatric disorders     
Aggression * 1  1/19 (5.26%)  0/17 (0.00%) 
Bradyphrenia * 1  1/19 (5.26%)  0/17 (0.00%) 
Insomnia * 1  2/19 (10.53%)  0/17 (0.00%) 
Irritability * 1  0/19 (0.00%)  1/17 (5.88%) 
Libido decreased * 1  1/19 (5.26%)  0/17 (0.00%) 
Negative thoughts * 1  1/19 (5.26%)  0/17 (0.00%) 
Renal and urinary disorders     
Pollakiuria * 1  1/19 (5.26%)  0/17 (0.00%) 
Reproductive system and breast disorders     
Dysmenorrhoea * 1  0/19 (0.00%)  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  1/19 (5.26%)  0/17 (0.00%) 
Nasal congestion * 1  1/19 (5.26%)  0/17 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  0/19 (0.00%)  1/17 (5.88%) 
Hyperhidrosis * 1  4/19 (21.05%)  0/17 (0.00%) 
Vascular disorders     
Hot flush * 1  2/19 (10.53%)  0/17 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
The study was initially designed to include 20 mg BID and 5 mg BID. Interim analysis of 20 mg BID/placebo supported the development of PF-02545920, and therefore, 5 mg BID was not enrolled.
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01806896     History of Changes
Other Study ID Numbers: A8241016
2012-004432-31 ( EudraCT Number )
First Submitted: March 6, 2013
First Posted: March 7, 2013
Results First Submitted: July 11, 2016
Results First Posted: December 14, 2017
Last Update Posted: December 14, 2017