Parkinson's Disease
Conditions
Keywords
Parkinson's disease
Brief summary
This study examines the efficacy of three doses of IPX066 as compared to placebo in Parkinson's disease.
Detailed description
A randomized, double-blind, placebo-controlled, fixed-dose, parallel-arm study of three doses of IPX066 versus placebo. Total of 427 subjects were screened and 381 were randomized and received one of the four treatment groups (1) placebo (N=92), (2) IPX066 145 mg LD (N=87) (3) IPX066 245 mg LD (N=104) (4) IPX066 390 mg LD (N=98) three times a day. Study duration is approximately 30 weeks for each subject including 4 weeks of titration (up to 3 weeks of dose escalation and I week of stabilization for safe escalation to the allocated dose), and 26 weeks of maintenance. During the titration phase: The following dose strengths were used to titrate up to the final three strengths that were assigned to the three IPX066 treatment arms. IPX066 95 mg LD capsule containing 95 mg LD and 23.75 mg CD. IPX066 145 mg LD capsule containing 145 mg LD and 36.25 mg CD. IPX066 195 mg LD capsule containing 195 mg LD and 48.75 mg CD. IPX066 245 mg LD capsule containing 245 mg LD and 61.25 mg CD. During the maintenance phase: IPX066 145 mg LD treatment arm received 145 mg LD and 36.25 mg CD. IPX066 245 mg LD treatment arm received 245 mg LD and 61.25 mg CD. IPX066 390 mg LD treatment arm received 390 mg LD and 97.50 mg CD. Primary efficacy outcome measure was change from baseline in the sum of UPDRS Part II and Part III scores at the end of study or last value reported if subject discontinued prematurely. Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score.
Interventions
DRUGPlacebo
Placebo
DRUGIPX066 95 mg LD
IPX066 capsule containing 95 mg LD/23.75 mg CD
DRUGIPX066 145 mg LD
IPX066 capsule containing 145 mg LD/36.25 mg CD
DRUGIPX066 195 mg LD
IPX066 capsule containing 195 mg LD/48.75 mg CD
DRUGIPX066 245 mg LD
IPX066 capsule containing 245 mg LD/61.25 mg CD
Sponsors
Impax Laboratories, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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. Able to understand and willing to voluntarily sign an informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) authorization or local equivalent if applicable. 2. Diagnosed with idiopathic PD. 3. LD-naïve: defined as subjects not exposed to LD or catechol-O-methyl transferase inhibitors for more than 30 days and the exposure is not within 4 weeks prior to study enrollment. 4. If currently taking anticholinergic therapy, amantadine, or a monoamine oxidase type B (MAO-B) inhibitor, maintains a stable regimen for at least 4 weeks prior to Baseline, and agrees to maintain the stable regimen throughout study participation. 5. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month after completing the study. 6. Able and willing to comply with the protocol, including availability for all scheduled clinic visits and telephone calls.
Exclusion criteria
1. Pregnant or breastfeeding. 2. Diagnosed with atypical Parkinsonism or any known secondary parkinsonian syndrome. 3. Prior functional neurosurgical treatment for PD or if such procedures are anticipated during study participation. 4. Use of nonselective MAO inhibitors. 5. Use of dopamine agonists within 30 days prior to Screening. 6. Unable to tolerate a placebo regimen, in the Investigator's opinion. 7. Treatment of psychosis with any antipsychotic. 8. History of seizure or epilepsy. 9. Active or prior medical condition or prior surgical procedure that would interfere with LD absorption. 10. History of narrow-angle glaucoma. 11. Subjects with a history of malignant melanoma. 12. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome. 13. Received any investigational medications during the 30 days prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30 | Week 30 | Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) + UPDRS Part III (Motor Examination) at Week 30 (End of Study). Unified Parkinson's Disease Rating Scale (UPDRS) - Four Parts Higher score values represent a worse outcome. Subscales II and III were summed: Part I: Mentation, Behavior and Mood - 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living - 13 questions 5-17 Score range: 0-52 Part III: Motor Examination - 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) - 11 questions Score range: 0-25 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score | Baseline and Week 30 (or End of Study) | Change from Baseline in Parkinson's disease Questionnaire 39 (PDQ-39) at Weeks 4, 9, 16, 23 and 30 or early discontinuation was collected. The PDQ-39 is a self-reported questionnaire consisting of 39 questions regarding the subjects mobility and the responses consist of Never (better in outcome), (value 0), Occasionally (value 1), Sometimes (value 2), , Often (value 3), and Always (value 4), (worse in outcome). The minimum possible score is 0 and the maximum is 156. The outcome measure calculated was the change from baseline to end of study in mean PDQ-39 score. Negative values indicate a better result. |
Countries
Canada, Estonia, Latvia, Lithuania, Romania, Ukraine, United States
Participant flow
Recruitment details
First patient enrolled: 4/13/2009 Last patient out 10/05/2010
Pre-assignment details
Following enrollment, subjects were randomized into one of the four treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo capsules were used | 92 |
| IPX066 145 mg LD IPX066 capsules containing 145 mg levodopa and 36.25 mg carbidopa | 87 |
| IPX066 245 mg LD IPX066 capsules containing 245 mg levodopa and 61.25 mg carbidopa | 104 |
| IPX066 390 mg LD IPX066 capsules containing 390 mg levodopa and 97.5 mg carbidopa | 98 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 | 15 | 15 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 12 | 4 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Overall Study | Noncompliance | 0 | 0 | 1 | 1 |
| Overall Study | Other | 1 | 1 | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | IPX066 390 mg LD | IPX066 245 mg LD | IPX066 145 mg LD |
|---|---|---|---|---|---|
| Age at Parkinson's disease onset | 63.7 years STANDARD_DEVIATION 9.48 | 63.0 years STANDARD_DEVIATION 10 | 63.0 years STANDARD_DEVIATION 9.38 | 63.6 years STANDARD_DEVIATION 10.43 | 61.7 years STANDARD_DEVIATION 10.71 |
| Age, Continuous | 65.4 years STANDARD_DEVIATION 9.43 | 64.8 years STANDARD_DEVIATION 9.55 | 64.8 years STANDARD_DEVIATION 9.32 | 65.2 years STANDARD_DEVIATION 9.73 | 63.8 years STANDARD_DEVIATION 9.81 |
| Duration of Parkinson's disease | 1.8 years STANDARD_DEVIATION 2.01 | 2.0 years STANDARD_DEVIATION 2.34 | 2.0 years STANDARD_DEVIATION 2.33 | 1.8 years STANDARD_DEVIATION 1.85 | 2.3 years STANDARD_DEVIATION 3.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 19 Participants | 4 Participants | 7 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 87 Participants | 345 Participants | 89 Participants | 91 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 17 Participants | 5 Participants | 6 Participants | 4 Participants |
| Hoehn and Yahr Stage Remaining | 16 units on a scale | 83 units on a scale | 22 units on a scale | 26 units on a scale | 19 units on a scale |
| Hoehn and Yahr Stage Stage I | 7 units on a scale | 40 units on a scale | 14 units on a scale | 13 units on a scale | 6 units on a scale |
| Hoehn and Yahr Stage Stage II | 69 units on a scale | 258 units on a scale | 62 units on a scale | 65 units on a scale | 62 units on a scale |
| MMSE | 28.9 units on a scale STANDARD_DEVIATION 1.18 | 28.9 units on a scale STANDARD_DEVIATION 1.21 | 28.9 units on a scale STANDARD_DEVIATION 1.18 | 28.7 units on a scale STANDARD_DEVIATION 1.21 | 29.0 units on a scale STANDARD_DEVIATION 1.27 |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 90 participants | 375 participants | 96 participants | 102 participants | 87 participants |
| Region of Enrollment Canada | 10 participants | 37 participants | 9 participants | 9 participants | 9 participants |
| Region of Enrollment Estonia | 3 participants | 11 participants | 3 participants | 3 participants | 2 participants |
| Region of Enrollment Latvia | 1 participants | 2 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Lithuania | 7 participants | 27 participants | 8 participants | 8 participants | 4 participants |
| Region of Enrollment Romania | 13 participants | 55 participants | 14 participants | 15 participants | 13 participants |
| Region of Enrollment Ukraine | 28 participants | 115 participants | 26 participants | 32 participants | 29 participants |
| Region of Enrollment United States | 30 participants | 134 participants | 38 participants | 37 participants | 29 participants |
| Sex: Female, Male Female | 40 Participants | 169 Participants | 44 Participants | 45 Participants | 40 Participants |
| Sex: Female, Male Male | 52 Participants | 212 Participants | 54 Participants | 59 Participants | 47 Participants |
| UPDRS Parts II and III Score | 36.3 units on a scale STANDARD_DEVIATION 11.89 | 36.7 units on a scale STANDARD_DEVIATION 13.63 | 36.3 units on a scale STANDARD_DEVIATION 13.04 | 38.1 units on a scale STANDARD_DEVIATION 15.63 | 36.1 units on a scale STANDARD_DEVIATION 13.56 |
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 | 26 / 92 | 27 / 87 | 47 / 104 | 48 / 98 |
| serious Total, serious adverse events | 3 / 92 | 4 / 87 | 5 / 104 | 2 / 98 |
Outcome results
Primary
Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30
Analysis of the Change from Baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) + UPDRS Part III (Motor Examination) at Week 30 (End of Study). Unified Parkinson's Disease Rating Scale (UPDRS) - Four Parts Higher score values represent a worse outcome. Subscales II and III were summed: Part I: Mentation, Behavior and Mood - 4 questions 1-4 Score range: 1-16 Part II: Activities of Daily Living - 13 questions 5-17 Score range: 0-52 Part III: Motor Examination - 19 questions 18-31 and 25 total assessments Score range: 0-100 Part IV: Complications of Therapy (In the past week) - 11 questions Score range: 0-25
Time frame: Week 30
Population: Analysis included all treated subjects with at least one efficacy measurement after dosing. Subjects who had no post-baseline efficacy assessments (N4) and those who had early termination assessments\>3 days after last dose and no other post-baseline measurements (N16) were not included in the efficacy analysis set. Randomized (381)-(4+16) = 361.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30 | -0.6 units on a scale | Standard Deviation 10.37 |
| IPX066 145mg LD | Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30 | -11.7 units on a scale | Standard Deviation 10.97 |
| IPX066 245 mg LD | Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30 | -12.9 units on a scale | Standard Deviation 11.42 |
| IPX066 390 mg LD | Change From Baseline in the Sum of UPDRS Part II + UPDRS Part III at Week 30 | -14.9 units on a scale | Standard Deviation 11.85 |
Secondary
Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score
Change from Baseline in Parkinson's disease Questionnaire 39 (PDQ-39) at Weeks 4, 9, 16, 23 and 30 or early discontinuation was collected. The PDQ-39 is a self-reported questionnaire consisting of 39 questions regarding the subjects mobility and the responses consist of Never (better in outcome), (value 0), Occasionally (value 1), Sometimes (value 2), , Often (value 3), and Always (value 4), (worse in outcome). The minimum possible score is 0 and the maximum is 156. The outcome measure calculated was the change from baseline to end of study in mean PDQ-39 score. Negative values indicate a better result.
Time frame: Baseline and Week 30 (or End of Study)
Population: Subjects who had no postbaseline efficacy assessments (N=4) and those who had early termination assessments \>3 days after last dose and no other postbaseline measurements (N=16) were not included in the efficacy analysis. 2 subjects without a baseline measurement, 1 each from 145mg and 390mg arm were also excluded. Randomized 381-4-16-2=359.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score | -4.4 score on a scale | Standard Deviation 12.18 |
| IPX066 145mg LD | Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score | -3.8 score on a scale | Standard Deviation 12.16 |
| IPX066 245 mg LD | Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score | -6.0 score on a scale | Standard Deviation 12.3 |
| IPX066 390 mg LD | Summary of Change From Baseline to End of Study in Mean Parkinson's Disease Questionnaire-39 (PDQ-39) Score | 0.6 score on a scale | Standard Deviation 11.1 |