Trial Outcomes & Findings for A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 (NCT NCT01130493)
NCT ID: NCT01130493
Last Updated: 2019-10-29
Results Overview
Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean percentage of "OFF" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.
COMPLETED
PHASE3
110 participants
3 days of data immediately prior to the end of each 2 week treatment period
2019-10-29
Participant Flow
Date first patient enrolled: March 22, 2011 Date last patient completed: January 12, 2012
Following enrollment, all subjects were converted from stable doses of CLE to IPX066 prior to randomization. Following dose conversion, subjects were randomized into one of the two treatment sequences.
Participant milestones
| Measure |
IPX066 Conversion
All subjects were converted to IPX066 during an open-label period
|
IPX066-Open-label IPX066 Washout-CLE-OLE
IPX066 (Per Protocol: Part 1 Period 1), Open-label washout IPX066, CLE (Per Protocol: Part 1 Period 2), OLE (Per Protocol: Part 2)
|
CLE-Open Label IPX066 Washout-IPX066-OLE
CLE (Per Protocol: Part 1 Period 1), Open-label washout IPX066, IPX066 (Per Protocol: Part 1 Period 2), OLE (Per Protocol: Part 2)
|
|---|---|---|---|
|
Open-label Dose Conversion to IPX066
STARTED
|
110
|
0
|
0
|
|
Open-label Dose Conversion to IPX066
COMPLETED
|
91
|
0
|
0
|
|
Open-label Dose Conversion to IPX066
NOT COMPLETED
|
19
|
0
|
0
|
|
Part 1: Double-blind Treatment Period 1
STARTED
|
0
|
48
|
43
|
|
Part 1: Double-blind Treatment Period 1
COMPLETED
|
0
|
46
|
43
|
|
Part 1: Double-blind Treatment Period 1
NOT COMPLETED
|
0
|
2
|
0
|
|
Part 1: Open-Label IPX066 Washout
STARTED
|
0
|
46
|
43
|
|
Part 1: Open-Label IPX066 Washout
COMPLETED
|
0
|
45
|
41
|
|
Part 1: Open-Label IPX066 Washout
NOT COMPLETED
|
0
|
1
|
2
|
|
Part 1: Double-blind Treatment Period 2
STARTED
|
0
|
45
|
41
|
|
Part 1: Double-blind Treatment Period 2
COMPLETED
|
0
|
45
|
39
|
|
Part 1: Double-blind Treatment Period 2
NOT COMPLETED
|
0
|
0
|
2
|
|
Part 2: OLE
STARTED
|
0
|
39
|
35
|
|
Part 2: OLE
COMPLETED
|
0
|
36
|
30
|
|
Part 2: OLE
NOT COMPLETED
|
0
|
3
|
5
|
Reasons for withdrawal
| Measure |
IPX066 Conversion
All subjects were converted to IPX066 during an open-label period
|
IPX066-Open-label IPX066 Washout-CLE-OLE
IPX066 (Per Protocol: Part 1 Period 1), Open-label washout IPX066, CLE (Per Protocol: Part 1 Period 2), OLE (Per Protocol: Part 2)
|
CLE-Open Label IPX066 Washout-IPX066-OLE
CLE (Per Protocol: Part 1 Period 1), Open-label washout IPX066, IPX066 (Per Protocol: Part 1 Period 2), OLE (Per Protocol: Part 2)
|
|---|---|---|---|
|
Open-label Dose Conversion to IPX066
Adverse Event
|
1
|
0
|
0
|
|
Open-label Dose Conversion to IPX066
Protocol Violation
|
3
|
0
|
0
|
|
Open-label Dose Conversion to IPX066
Lack of Efficacy
|
7
|
0
|
0
|
|
Open-label Dose Conversion to IPX066
Withdrawal by Subject
|
7
|
0
|
0
|
|
Open-label Dose Conversion to IPX066
Diary imcomplete
|
1
|
0
|
0
|
|
Part 1: Double-blind Treatment Period 1
Protocol Violation
|
0
|
1
|
0
|
|
Part 1: Double-blind Treatment Period 1
Lack of Efficacy
|
0
|
1
|
0
|
|
Part 1: Open-Label IPX066 Washout
Lack of Efficacy
|
0
|
1
|
0
|
|
Part 1: Open-Label IPX066 Washout
Adverse Event
|
0
|
0
|
1
|
|
Part 1: Open-Label IPX066 Washout
Withdrawal by Subject
|
0
|
0
|
1
|
|
Part 1: Double-blind Treatment Period 2
Withdrawal by Subject
|
0
|
0
|
1
|
|
Part 1: Double-blind Treatment Period 2
Noncompliance
|
0
|
0
|
1
|
|
Part 2: OLE
Adverse Event
|
0
|
2
|
1
|
|
Part 2: OLE
Withdrawal by Subject
|
0
|
1
|
4
|
Baseline Characteristics
A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066
Baseline characteristics by cohort
| Measure |
All Study Participants
n=91 Participants
Participants who were randomized to receive either IPX066 or IR CD-LD in Part 1 of the study and then IPX066 in Part 2 (open-label extension).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
50 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
41 Participants
n=5 Participants
|
|
Age, Continuous
|
64.1 years
STANDARD_DEVIATION 9.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
79 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
89 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
44 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
21 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 days of data immediately prior to the end of each 2 week treatment periodPopulation: Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2
Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean percentage of "OFF" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.
Outcome measures
| Measure |
IPX066
n=83 Participants
Participants who received IPX066 in either Period 1 or Period 2
|
CLE (Active Comparator)
n=83 Participants
Participants who received CLE in either Period 1 or Period 2
|
Number of Participants Who Had no Preference
Participants who completed both treatment periods and who did not indicate a preference for either treatment
|
|---|---|---|---|
|
Percentage of "OFF" Time During Waking Hours
|
23.98 Percent
Standard Deviation 16.242
|
32.48 Percent
Standard Deviation 21.917
|
—
|
SECONDARY outcome
Timeframe: 3 days of data immediately prior to the end of each 2 week treatment periodPopulation: Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2
Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "Off" Time During Waking Hours was calculated. "Off" Time is Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.
Outcome measures
| Measure |
IPX066
n=83 Participants
Participants who received IPX066 in either Period 1 or Period 2
|
CLE (Active Comparator)
n=83 Participants
Participants who received CLE in either Period 1 or Period 2
|
Number of Participants Who Had no Preference
Participants who completed both treatment periods and who did not indicate a preference for either treatment
|
|---|---|---|---|
|
Total "OFF" Time During Waking Hours
|
3.82 hours
Standard Deviation 2.558
|
5.22 hours
Standard Deviation 3.672
|
—
|
SECONDARY outcome
Timeframe: 3 days of data immediately prior to the end of each 2 week treatment periodPopulation: Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2
Using a Parkinson's disease diary, subjects recorded a state of "asleep", "OFF", "ON without dyskinesia," "ON with non-troublesome dyskinesia," or "ON with troublesome dyskinesia" every 30 minutes over a 24-hour day for the last 3 days of each double-blind crossover treatment period. Mean Total "On" with No Troublesome Dyskinesia was calculated. "On" Time is when medication is providing benefit with regard to mobility, slowness, and stiffness.
Outcome measures
| Measure |
IPX066
n=83 Participants
Participants who received IPX066 in either Period 1 or Period 2
|
CLE (Active Comparator)
n=83 Participants
Participants who received CLE in either Period 1 or Period 2
|
Number of Participants Who Had no Preference
Participants who completed both treatment periods and who did not indicate a preference for either treatment
|
|---|---|---|---|
|
Total "On" With No Troublesome Dyskinesia
|
11.36 hours
Standard Deviation 3.259
|
9.98 hours
Standard Deviation 3.764
|
—
|
SECONDARY outcome
Timeframe: End of each double-blind treatment period.Population: Participants who completed both treatment periods
Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). Part II consists of 14 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 72. Part III consists of 27 questions, each ranges from 0 (Normal/None) - 4 (Worst) with a total score of 0 - 108. The UPDRS Part II Plus Part III scores ranged from 0 (no problems with daily living or mobility) to 180 (severe problems with daily living and mobility.
Outcome measures
| Measure |
IPX066
n=84 Participants
Participants who received IPX066 in either Period 1 or Period 2
|
CLE (Active Comparator)
n=84 Participants
Participants who received CLE in either Period 1 or Period 2
|
Number of Participants Who Had no Preference
Participants who completed both treatment periods and who did not indicate a preference for either treatment
|
|---|---|---|---|
|
UPDRS Part II Plus Part III
|
29.3 Scores on a scale
Standard Deviation 15.02
|
31.7 Scores on a scale
Standard Deviation 14.89
|
—
|
SECONDARY outcome
Timeframe: End of Study (week 11)Population: Participants who completed both treatment periods
Subjects who completed both treatments were asked to indicate a preference for Treatment Period 1 or Treatment Period 2 or no preference. Preferences for a particular treatment period were mapped to the associated treatment and reported.
Outcome measures
| Measure |
IPX066
n=84 Participants
Participants who received IPX066 in either Period 1 or Period 2
|
CLE (Active Comparator)
n=84 Participants
Participants who received CLE in either Period 1 or Period 2
|
Number of Participants Who Had no Preference
n=84 Participants
Participants who completed both treatment periods and who did not indicate a preference for either treatment
|
|---|---|---|---|
|
Subject Preference
|
44 Participants
|
23 Participants
|
17 Participants
|
Adverse Events
Dose Conversion
IPX066
CLE (Active Comparator)
Washout
Serious adverse events
| Measure |
Dose Conversion
n=91 participants at risk
Participants were to be converted from stable doses of CLE to open-label IPX066 over a 6-week period
|
IPX066
n=89 participants at risk
Participants first received 2 weeks of IPX066 followed by an approximate 7-day washout period of IPX066 treatment followed by another 2 weeks of CLE.
|
CLE (Active Comparator)
n=88 participants at risk
Participants first received 2 weeks of CLE followed by an approximate 7-day washout period of IPX066 treatment followed by another 2 weeks of IPX066.
|
Washout
n=89 participants at risk
Participants receive open-label IPX066 for 1 week
|
|---|---|---|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
1.1%
1/91 • Number of events 1
|
0.00%
0/89
|
0.00%
0/88
|
0.00%
0/89
|
|
Gastrointestinal disorders
Gastrointestinal Toxicity
|
1.1%
1/91 • Number of events 1
|
0.00%
0/89
|
0.00%
0/88
|
0.00%
0/89
|
|
Gastrointestinal disorders
Constipation
|
1.1%
1/91 • Number of events 1
|
0.00%
0/89
|
0.00%
0/88
|
0.00%
0/89
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/91
|
0.00%
0/89
|
0.00%
0/88
|
1.1%
1/89 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercalemia
|
1.1%
1/91 • Number of events 1
|
0.00%
0/89
|
0.00%
0/88
|
0.00%
0/89
|
|
Nervous system disorders
Sciatica
|
0.00%
0/91
|
1.1%
1/89 • Number of events 1
|
0.00%
0/88
|
0.00%
0/89
|
Other adverse events
| Measure |
Dose Conversion
n=91 participants at risk
Participants were to be converted from stable doses of CLE to open-label IPX066 over a 6-week period
|
IPX066
n=89 participants at risk
Participants first received 2 weeks of IPX066 followed by an approximate 7-day washout period of IPX066 treatment followed by another 2 weeks of CLE.
|
CLE (Active Comparator)
n=88 participants at risk
Participants first received 2 weeks of CLE followed by an approximate 7-day washout period of IPX066 treatment followed by another 2 weeks of IPX066.
|
Washout
n=89 participants at risk
Participants receive open-label IPX066 for 1 week
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Fall
|
2.2%
2/91 • Number of events 2
|
1.1%
1/89 • Number of events 1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/89
|
|
Gastrointestinal disorders
Nausea
|
6.6%
6/91 • Number of events 6
|
1.1%
1/89 • Number of events 1
|
0.00%
0/88
|
0.00%
0/89
|
|
Infections and infestations
Upper Respiratory Infection
|
2.2%
2/91 • Number of events 2
|
0.00%
0/89
|
0.00%
0/88
|
0.00%
0/89
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
2/91 • Number of events 2
|
1.1%
1/89 • Number of events 1
|
0.00%
0/88
|
0.00%
0/89
|
|
Nervous system disorders
Dyskinesia
|
1.1%
1/91 • Number of events 1
|
4.5%
4/89 • Number of events 4
|
0.00%
0/88
|
1.1%
1/89 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
1.1%
1/91 • Number of events 1
|
3.4%
3/89 • Number of events 3
|
0.00%
0/88
|
0.00%
0/89
|
|
Psychiatric disorders
Confusional State
|
0.00%
0/91
|
3.4%
3/89 • Number of events 3
|
0.00%
0/88
|
0.00%
0/89
|
Additional Information
Kaihong Jiang, Senior Director, Head of Biometrics
Impax Laboratories, LLC
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place