A Study To Evaluate The Safety And Efficacy Of IPX066 In Subjects With Parkinson's Disease

Study Overview
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Brief Summary
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This study examines the efficacy of three doses of IPX066 as compared to placebo in Parkinson's disease.

Detailed Description
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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.

Official Title
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A Placebo-Controlled Study To Evaluate The Safety And Efficacy Of IPX066 In Subjects With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: IPX066 95 mg LD
* Drug: IPX066 145 mg LD
* Drug: IPX066 195 mg LD
* Drug: IPX066 245 mg LD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Diagnosed with idiopathic PD. 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. 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. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month after completing the study. Able and willing to comply with the protocol, including availability for all scheduled clinic visits and telephone calls. Exclusion Criteria: Pregnant or breastfeeding. Diagnosed with atypical Parkinsonism or any known secondary parkinsonian syndrome. Prior functional neurosurgical treatment for PD or if such procedures are anticipated during study participation. Use of nonselective MAO inhibitors. Use of dopamine agonists within 30 days prior to Screening. Unable to tolerate a placebo regimen, in the Investigator's opinion. Treatment of psychosis with any antipsychotic. History of seizure or epilepsy. Active or prior medical condition or prior surgical procedure that would interfere with LD absorption. History of narrow-angle glaucoma. Subjects with a history of malignant melanoma. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome. Received any investigational medications during the 30 days prior to Screening.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One Placebo capsule was given TID for the first 21 days. Two placebo capsules were given TID on days 22 till end of study (week 30). | Drug: Placebo<br>* Placebo<br>|
| Experimental: IPX066 145 mg LD<br>One IPX066 95 mg LD was given TID on days 1-3. One IPX066 145 mg LD was given TID on days 4-21. One IPX066 145 mg LD and one placebo capsule were given TID on days 22 till end of study (week 30). | Drug: Placebo<br>* Placebo<br>Drug: IPX066 95 mg LD<br>* IPX066 capsule containing 95 mg LD/23.75 mg CD<br>* Other names: CD-LD ER 95 mg;Drug: IPX066 145 mg LD<br>* IPX066 capsule containing 145 mg LD/36.25 mg CD<br>* Other names: CD-LD ER 145 mg;|
| Experimental: IPX066 245 mg LD<br>One IPX066 95 mg LD was given TID on days 1-3. One IPX066 145 mg LD was given TID on days 4-7. One IPX066 195 mg LD was given TID on days 8-14. One IPX066 245 mg LD was given TID on days 15-21. One IPX066 245 mg LD and one placebo capsule were given TID on days 22 till end of study (week 30). | Drug: Placebo<br>* Placebo<br>Drug: IPX066 95 mg LD<br>* IPX066 capsule containing 95 mg LD/23.75 mg CD<br>* Other names: CD-LD ER 95 mg;Drug: IPX066 145 mg LD<br>* IPX066 capsule containing 145 mg LD/36.25 mg CD<br>* Other names: CD-LD ER 145 mg;Drug: IPX066 195 mg LD<br>* IPX066 capsule containing 195 mg LD/48.75 mg CD<br>* Other names: CD-LD ER 195 mg;Drug: IPX066 245 mg LD<br>* IPX066 capsule containing 245 mg LD/61.25 mg CD<br>* Other names: CD-LD ER 245 mg;|
| Experimental: IPX066 390 mg LD<br>One IPX066 95 mg LD was given TID on days 1-3. One IPX066 145 mg LD was given TID on days 4-7. One IPX066 195 mg LD was given TID on days 8-14. One IPX066 245 mg LD was given TID on days 15-21. Two IPX066 195 mg LD capsules were given TID on days 22 till end of study (week 30). | Drug: IPX066 95 mg LD<br>* IPX066 capsule containing 95 mg LD/23.75 mg CD<br>* Other names: CD-LD ER 95 mg;Drug: IPX066 145 mg LD<br>* IPX066 capsule containing 145 mg LD/36.25 mg CD<br>* Other names: CD-LD ER 145 mg;Drug: IPX066 195 mg LD<br>* IPX066 capsule containing 195 mg LD/48.75 mg CD<br>* Other names: CD-LD ER 195 mg;Drug: IPX066 245 mg LD<br>* IPX066 capsule containing 245 mg LD/61.25 mg CD<br>* Other names: CD-LD ER 245 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 30 (or End of Study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease