A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066

Study Overview
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Brief Summary
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This is a study to compare the efficacy of IPX066 and CLE in subjects with advanced Parkinson's disease.

Detailed Description
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This is a randomized, double-blind, double-dummy, 2 treatment, 2-period crossover study followed by an open-label extension study period.

Official Title
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A Study to Compare IPX066 and Carbidopa/Levodopa/Entacapone (CLE) Followed by an Open-Label Safety Study of IPX066 in Advanced Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: IPX066
* Drug: CLE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with idiopathic Parkinson's Disease (PD). At least 30 years old at the time of PD diagnosis. 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. Able to differentiate on state from off state. Have predictable off periods. 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. Agrees to use a medically acceptable method of contraception throughout the study and for 1 month afterward. Exclusion Criteria: Diagnosed with atypical Parkinsonism or any known secondary Parkinsonian syndrome. Nonresponsive to LD therapy. Prior functional neurosurgical treatment for PD (e.g., ablation or deep brain stimulation) or if such procedures are anticipated during study participation. 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. Allergy or hypersensitivity to CD, LD, entacapone, riboflavin, Yellow Dye #5 (tartrazine), citrus fruit or grape juice. History of or currently active psychosis. Active or prior medical conditions such as peptic ulcers or prior surgical (e.g., bowel) procedures that would interfere with LD absorption. Active or history of narrow-angle glaucoma. History of malignant melanoma or a suspicious undiagnosed skin lesion. History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias, upper gastrointestinal hemorrhage, or neuroleptic malignant syndrome or nontraumatic rhabdomyolysis. Received any investigational medications during the 4 weeks prior to Screening. Unable to swallow large pills (e.g., large vitamin pills). Pregnant or breastfeeding. Subjects who are unable to complete a symptom diary.

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: IPX066-CLE-OLE<br>Dose conversion from CLE to IPX066, IPX066 (Part 1 Period 1), Open-label IPX066, CLE (Part 1 Period 2), OLE (Part 2) | Drug: IPX066<br>* experimental product<br>* Other names: extended-release carbidopa-levodopa;Drug: CLE<br>* active comparator<br>* Other names: carbidopa/levodopa/entacapone;|
| Other: CLE-IPX066-OLE<br>Dose conversion from CLE to IPX066, CLE (Part 1 Period 1), Open-label IPX066, IPX066 (Part 1 Period 2), OLE (Part 2) | Drug: IPX066<br>* experimental product<br>* Other names: extended-release carbidopa-levodopa;Drug: CLE<br>* active comparator<br>* Other names: carbidopa/levodopa/entacapone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 days of data immediately prior to the end of each 2 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 days of data immediately prior to the end of each 2 week treatment period | 
| 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. | 3 days of data immediately prior to the end of each 2 week treatment period | 
| 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. | End of each double-blind treatment period. | 
| 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. | End of Study (week 11) |