Parkinson's Disease
Conditions
Brief summary
This is a study to compare the efficacy of IPX066 and CLE in subjects with advanced Parkinson's disease.
Detailed description
This is a randomized, double-blind, double-dummy, 2 treatment, 2-period crossover study followed by an open-label extension study period.
Sponsors
Impax Laboratories, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with idiopathic Parkinson's Disease (PD). 2. At least 30 years old at the time of PD diagnosis. 3. Currently being treated with carbidopa/levodopa/entacapone (CLE) and on a stable regimen of conventional LD for at least 4 weeks and: * Requiring a total daily levodopa (LD) dose of at least 400 mg * Having a minimum dosing frequency of four times per day. * Individual CD-LD or CLE doses that contain an LD dose which is a multiple of 50 mg. 4. Able to differentiate on state from off state. 5. Have predictable off periods. 6. Amantadine, anticholinergics, selective monoamine oxidase (MAO) type B inhibitors (e.g., selegiline, rasagiline) or dopamine agonists are allowed as long as the doses and regimens have been stable for at least 4 weeks prior to Screening and the therapy is intended to be constant throughout the course of the study. 7. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month afterward.
Exclusion criteria
1. Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome. 2. Nonresponsive to LD therapy. 3. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) or if such procedures are anticipated during study participation. 4. Received within 4 weeks of Screening or planning to take during participation in the clinical study: any controlled-release LD product, tolcapone, apomorphine, nonselective MAO inhibitors, or antipsychotics including neuroleptic agents for the purpose of treating psychosis or bipolar disorder. 5. Allergy or hypersensitivity to CD, LD, entacapone, riboflavin, Yellow Dye #5 (tartrazine), citrus fruit or grape juice. 6. History of or currently active psychosis. 7. Active or prior medical conditions such as peptic ulcers or prior surgical (e.g., bowel) procedures that would interfere with LD absorption. 8. Active or history of narrow-angle glaucoma. 9. History of malignant melanoma or a suspicious undiagnosed skin lesion. 10. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome or nontraumatic rhabdomyolysis. 11. Received any investigational medications during the 4 weeks prior to Screening. 12. Unable to swallow large pills (e.g., large vitamin pills). 13. Pregnant or breastfeeding. 14. Subjects who are unable to complete a symptom diary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of OFF Time During Waking Hours | 3 days of data immediately prior to the end of each 2 week treatment period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total OFF Time During Waking Hours | 3 days of data immediately prior to the end of each 2 week treatment period | 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. |
| Total On With No Troublesome Dyskinesia | 3 days of data immediately prior to the end of each 2 week treatment period | 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. |
| UPDRS Part II Plus Part III | End of each double-blind treatment period. | 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. |
| Subject Preference | End of Study (week 11) | 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. |
Countries
France, Germany, Italy, United States
Participant flow
Recruitment details
Date first patient enrolled: March 22, 2011 Date last patient completed: January 12, 2012
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Study 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). | 91 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-label Dose Conversion to IPX066 | Adverse Event | 1 | 0 | 0 |
| Open-label Dose Conversion to IPX066 | Diary imcomplete | 1 | 0 | 0 |
| Open-label Dose Conversion to IPX066 | Lack of Efficacy | 7 | 0 | 0 |
| Open-label Dose Conversion to IPX066 | Protocol Violation | 3 | 0 | 0 |
| Open-label Dose Conversion to IPX066 | Withdrawal by Subject | 7 | 0 | 0 |
| Part 1: Double-blind Treatment Period 1 | Lack of Efficacy | 0 | 1 | 0 |
| Part 1: Double-blind Treatment Period 1 | Protocol Violation | 0 | 1 | 0 |
| Part 1: Double-blind Treatment Period 2 | Noncompliance | 0 | 0 | 1 |
| Part 1: Double-blind Treatment Period 2 | Withdrawal by Subject | 0 | 0 | 1 |
| Part 1: Open-Label IPX066 Washout | Adverse Event | 0 | 0 | 1 |
| Part 1: Open-Label IPX066 Washout | Lack of Efficacy | 0 | 1 | 0 |
| Part 1: Open-Label IPX066 Washout | Withdrawal by Subject | 0 | 0 | 1 |
| Part 2: OLE | Adverse Event | 0 | 2 | 1 |
| Part 2: OLE | Withdrawal by Subject | 0 | 1 | 4 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 41 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 9.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 89 Participants |
| Region of Enrollment Germany | 21 participants |
| Region of Enrollment Italy | 26 participants |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 91 | 13 / 89 | 2 / 88 | 1 / 89 |
| serious Total, serious adverse events | 2 / 91 | 1 / 89 | 0 / 88 | 1 / 89 |
Outcome results
Primary
Percentage of OFF Time During Waking Hours
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.
Time frame: 3 days of data immediately prior to the end of each 2 week treatment period
Population: Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | Percentage of OFF Time During Waking Hours | 23.98 Percent | Standard Deviation 16.242 |
| CLE (Active Comparator) | Percentage of OFF Time During Waking Hours | 32.48 Percent | Standard Deviation 21.917 |
Secondary
Subject Preference
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.
Time frame: End of Study (week 11)
Population: Participants who completed both treatment periods
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IPX066 | Subject Preference | 44 Participants |
| CLE (Active Comparator) | Subject Preference | 23 Participants |
| Number of Participants Who Had no Preference | Subject Preference | 17 Participants |
Secondary
Total OFF Time During Waking Hours
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.
Time frame: 3 days of data immediately prior to the end of each 2 week treatment period
Population: Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | Total OFF Time During Waking Hours | 3.82 hours | Standard Deviation 2.558 |
| CLE (Active Comparator) | Total OFF Time During Waking Hours | 5.22 hours | Standard Deviation 3.672 |
Secondary
Total On With No Troublesome Dyskinesia
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.
Time frame: 3 days of data immediately prior to the end of each 2 week treatment period
Population: Participants who completed both treatment periods and completed PD diary for both Period 1 and Period 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | Total On With No Troublesome Dyskinesia | 11.36 hours | Standard Deviation 3.259 |
| CLE (Active Comparator) | Total On With No Troublesome Dyskinesia | 9.98 hours | Standard Deviation 3.764 |
Secondary
UPDRS Part II Plus Part III
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.
Time frame: End of each double-blind treatment period.
Population: Participants who completed both treatment periods
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IPX066 | UPDRS Part II Plus Part III | 29.3 Scores on a scale | Standard Deviation 15.02 |
| CLE (Active Comparator) | UPDRS Part II Plus Part III | 31.7 Scores on a scale | Standard Deviation 14.89 |