Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Compare Pharmacokinetics and Pharmacodynamics of IPX066 to Standard Carbidopa-Levodopa

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: NCT00869791
Recruitment Status : Completed
First Posted : March 26, 2009
Results First Posted : March 31, 2017
Last Update Posted : May 9, 2017
Sponsor:
Information provided by (Responsible Party):
IMPAX Laboratories, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Drug: IPX066
Drug: IR CD-LD
Enrollment 27
Recruitment Details 35 subjects were screened. 8 were screen failures (did to not meet inclusion/exclusion criteria) and 27 were randomized. Date of first patient enrolled: November 25, 2008 Date last patient completed: June 11, 2009 The study was conducted at 6 sites in the United States.
Pre-assignment Details 27 participants were enrolled, treated and completed the treatment with this protocol.
Arm/Group Title IPX066 First (7 Days), Washout (7 Days) Then IR CD-LD (7 Days) IR CD-LD First ( 7 Days), Washout (7 Days) Then IPX066 (7days)
Hide Arm/Group Description In this arm there were 2 treatment periods of one week each. During period 1, 14 subjects received 7 days of IPX066 first. Then subjects returned to their pre-study regimen during the washout period of approximately 1 week. This was followed by Period 2. During period 2, the 14 subjects received IR CD-LD for 7 days. In this arm there were 2 treatment periods of one week each. During period 1, 13 subjects received 7 days of IR CD-LD first. Then subjects returned to their pre-study regimen during the washout period of approximately 1 week. This was followed by Period 2. During period 2, the 13 subjects received IPX066 for 7 days.
Period Title: Period 1 Treatment for 7 Days
Started 14 13
Completed 14 13
Not Completed 0 0
Period Title: Period 2 Treatment for 7 Days
Started 14 13
Completed 14 13
Not Completed 0 0
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants who were randomized to receive either IPX066 or IR CD-LD
Overall Number of Baseline Participants 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants
62.7  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Female
6
  22.2%
Male
21
  77.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Hispanic or Latino
1
   3.7%
Not Hispanic or Latino
26
  96.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
  11.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
24
  88.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants
27
1.Primary Outcome
Title Pharmacokinetics Measurements to Determine Cmax for Carbidopa (CD) and Levodopa (LD) Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
Hide Description For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Maximum (peak) drug concentration (Cmax in nanograms/milliliter) was estimated using Single-Dose data and Multiple-Dose data.
Time Frame Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm 2 (CD-LD IR first, washout, then IPX066)
Hide Outcome Measure Data
Hide Analysis Population Description
The study was designed to assess the single and multiple-dose PK and PD of IPX066 and IR CD-LD in subjects with advanced PD.14 subjects first received IPX066 (Period 1), then IR CD-LD (Period 2). 13 Subjects first received IR CD-LD (Period 1), then IPX066 (Period 2). All 27 subjects that were treated in the study were included in the PK analyses.
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: nanogram/milliliter
CD Cmax, Single-Dose 238.852  (91.004) 146.848  (58.787)
CD Cmax, Multiple-Dose 313.222  (167.924) 167.515  (51.204)
LD Cmax, Single-Dose 3000.000  (1301.608) 2356.444  (1080.541)
LD Cmax, Multiple-Dose 3807.037  (1547.120) 2761.852  (1002.984)
2.Primary Outcome
Title Pharmacokinetics Measurements to Determine Tmax for Levodopa and Carbidopa Plasma Concentrations From Samples Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Both Treatment Arms.
Hide Description For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Time of maximum drug concentration (Tmax in hours) was estimated using Single-Dose data and Multiple-Dose data.
Time Frame Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
Hide Outcome Measure Data
Hide Analysis Population Description
The study was designed to assess the single and multiple-dose PK and PD of IPX066 and IR CD-LD in subjects with advanced PD. 14 subjects first received IPX066 (Period 1), then IR CD-LD (Period 2). 13 Subjects first received IR CD-LD (Period 1), then IPX066 (Period 2). All 27 subjects that were treated in the study were included in the PK analyses.
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Hours
CD Tmax Single-Dose 2.944  (0.5604) 2.296  (0.6086)
CD Tmax Multiple-Dose 3.815  (2.6390) 5.685  (3.5711)
LD Tmax Single-Dose 2.037  (1.0735) 0.870  (0.4921)
LD Tmax Multiple-Dose 4.407  (3.7597) 3.611  (4.2161)
3.Primary Outcome
Title Pharmacokinetics Measurements to Determine Area Under the Concentration-time Curve for the Dosing Interval for LD and CD Concentrations From Blood Collected Pre-dose and at Different Time Points on Day 1 and Day 8 of Periods 1 and 2 of Treatment Arms.
Hide Description For both treatment arms: Sequence 1 (IPX066, Washout, then IR CD-LD) and Sequence 2 (IR CD-LD, Washout, IPX066), blood samples for measurement of LD and CD plasma concentrations were collected pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, and 8 hours after dosing on Day 1 (referred to as Single-Dose data); and at pre-dose, 0.5, 1,1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours after dosing on Day 8 (referred to as Multiple-Dose data). Area under the concentration-time curve for the dosing interval (AUC Tau) in hour*nanogram/milliliter was estimated using Single-Dose data and Multiple-Dose data.
Time Frame Day 1 and on Day 8 after a week of intervention in each treatment arm: Arm 1 (IPX066 first, washout, then CD-LD IR) and Arm2 (CD-LD IR first, washout, then IPX066
Hide Outcome Measure Data
Hide Analysis Population Description
The study was designed to assess the single and multiple-dose PK and PD of IPX066 and IR CD-LD in subjects with advanced PD. 14 subjects first received IPX066 (Period 1), then IR CD-LD (Period 2). 13 Subjects first received IR CD-LD (Period 1), then IPX066 (Period 2). All 27 subjects that were treated in the study were included in the PK analyses.
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: hour*nanogram/milliliter
CD AUC Tau, Single-Dose 917.067  (373.9147) 401.694  (177.8239)
CD AUC Tau, Multiple-Dose 1344.436  (818.1622) 449.584  (273.8498)
LD AUC Tau, Single-Dose 10902.194  (4619.2284) 3881.298  (1586.9059)
LD AUC Tau, Multiple-Dose 13903.380  (6990.0405) 4167.151  (1799.2567)
4.Secondary Outcome
Title 8-Hour Efficacy Using Day 1 Tapping
Hide Description Improvement in "Tapping: has been used as a surrogate endpoint for assessing subject being “On". Finger Tapping: the number of times the subject could tap two counter keys 20 cm apart alternately in 1 minute with the most affected arm assessed every 30 minutes on Day 1. Subjects performed the 60-second tapping measurement three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period on Day 1 of each treatment period. More hours “On” during treatment represented better outcome. For the Tapping measurement, the protocol defined a 20% change from the average of the predose measurements as the time to “On.” Each half-hour interval counted as 0.5 hour. Any measurement below a 20% improvement was considered time “Not On.” If patient required redosing then primary analyses adjusted for redosing in calculating the results.
Time Frame Day 1 of each treatment period - three times prior to dosing in the clinic, and at half-hour intervals through the 8-hour measurement period
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of covariance was the primary analysis conducted on the mean total Taps across the 8-hour measurement period, with the average of the three predose Tapping measurement values as a covariate.
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: Hours
4.74  (2.843) 2.98  (2.436)
5.Secondary Outcome
Title 8-Hour Efficacy Using Day 1 Unified Parkinson’s Disease Rating Scale Part III Score
Hide Description To determine efficacy on Day 1 the UPDRS (unified Parkinson's disease rating) Part III score, a clinician-scored measure of motor function, was collected immediately predose and 1, 2, 3, 4, 5, 6, 7 and 8 h post dose. The UPDRS Part III motor exam analyzes multiple motor functions like speech, facial expression, tremor, rigidity, movement, posture, gait etc. Each parameter is assigned values from 0 to 4, with 0 being normal and 4 being the most affected. The total range is 0 - 108, with lower scores indicating a better outcome.The average of post dose was calculated for day 1.
Time Frame Pre dosing and at hourly intervals through the 8-hour measurement period on day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of covariance was the primary analysis conducted on the mean UPDRS Part III across the 8-hour measurement period, with the predose UPDRS Part III value as a covariate. This analysis was repeated at each timepoint for completeness.
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: UPDRS Part III Motor Score
21.6  (9.81) 25.5  (9.54)
6.Secondary Outcome
Title Result Summary of Day 1 Dyskinesia Evaluated by Investigator Assessment for Each Treatment Period
Hide Description To determine 8h efficacy on Day 1 the on site investigator assessments of "ON", "OFF" and "state of dyskinesia" for each subject was collected predose (-1, -0.5, and 0 hours) every 30 min for up to 8 hours after dosing . For all subjects duration of (1) OFF time (2) ON time without dyskinesia, (3) ON time with non-troublesome dyskinesia and (4) ON time with troublesome dyskinesia was calculated for both treatments. Definition of “ON” was based on a 20% change from predose measure, and the results were analyzed in the standard manner of a two way crossover design. The trial inclusion criteria included ability of subject to differentiate “ON” state from “OFF” state per investigator’s assessment.
Time Frame Predose and then every 30 min upto 8 h after dosing on Day of 1 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
For determining motor assessment of dyskinesia evaluated by investigator assessment a mixed-effect model was used with treatment, sequence, and period as factors and subjects within sequence as error term. The primary analysis was performed on the average of all times collected half hourly. Data for two patients was not collected, N25 instead of 27
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 25 25
Mean (Standard Deviation)
Unit of Measure: Hours
OFF time 1.90  (1.588) 4.44  (1.364)
ON time without dyskinesia 2.94  (2.468) 2.36  (1.840)
ON time with non-troublesome dyskinesia 2.62  (2.242) 0.90  (0.968)
ON time with troublesome dyskinesia 0.54  (1.070) 0.28  (0.830)
7.Secondary Outcome
Title "Off" Time Hours Reported by Subjects Using Parkinson's Patient Diary
Hide Description Subjects recorded state of ”OFF” time using the Parkinson's Patient Diary
Time Frame Last 3 days of each treatment period, every 30 minutes over a 24-hour day beginning at 6:00 AM
Hide Outcome Measure Data
Hide Analysis Population Description
All treated patients
Arm/Group Title IPX066 IR CD-LD
Hide Arm/Group Description:
All participants who received IPX066 in either study period
All participants who received IR CD-LD in either study period
Overall Number of Participants Analyzed 27 27
Mean (Standard Deviation)
Unit of Measure: hours
3.83  (2.80) 5.83  (2.92)
Time Frame At each of the 4 study visits and follow-up with the subject by phone within 1 week of study exit.
Adverse Event Reporting Description Safety measures (electrocardiograms [ECGs], clinical laboratory tests, vital signs, adverse events [AEs], and concomitant medications) were evaluated over the course of the study. The Investigators were specified in the protocol to follow each AE until resolution or stabilization and in accordance with Good Clinical Practice (GCP). Follow-up on these AEs were be recorded on the source documents and reported to IMPAX.
 
Arm/Group Title IPX066 CD-LD IR
Hide Arm/Group Description All participants who received IPX066 in either study period All participants who received IR CD-LD in either study period
All-Cause Mortality
IPX066 CD-LD IR
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IPX066 CD-LD IR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/27 (0.00%)      0/27 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
IPX066 CD-LD IR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/27 (11.11%)      3/27 (11.11%)    
Gastrointestinal disorders     
Feeling of Warth in Abdomen  1  1/27 (3.70%)  1 0/27 (0.00%)  0
General disorders     
Fatigue  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Infections and infestations     
Common Cold  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders     
Choreiform Movements  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Nervous system disorders     
Sleepy  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Headache - Frontal  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Dizziness after Taking Medication  1  0/27 (0.00%)  0 1/27 (3.70%)  1
Anxiety  1  1/27 (3.70%)  1 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
The limitations of this study include its relatively small size, multiple statistical testing, short study durations, and open-label design.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Michelle Landolfi, PhD. Sr. Director, Regulatory Affairs
Organization: Impax Laboratories, Inc.
Phone: (510) 240-6496
Responsible Party: IMPAX Laboratories, Inc.
ClinicalTrials.gov Identifier: NCT00869791     History of Changes
Other Study ID Numbers: IPX066-B08-11
First Submitted: March 24, 2009
First Posted: March 26, 2009
Results First Submitted: January 25, 2016
Results First Posted: March 31, 2017
Last Update Posted: May 9, 2017