A Study to Assess the PK and Pharmacodynamics of IPX203 in Subjects With Advanced Parkinson's Disease

Study Overview
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Brief Summary
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Primary Objective: To compare the pharmacokinetics (PK) of single and multiple doses of IPX203 with Immediate release carbidopa-levodopa (IR CD-LD) in subjects with advanced Parkinson's disease (PD). Secondary Objectives: To compare the pharmacodynamics of single and multiple doses of IPX203 with IR CD-LD. To compare the efficacy of IPX203 with IR CD-LD following multiple doses. To evaluate the safety of IPX203.

Detailed Description
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IPX203 is an investigational product containing CD-LD. IPX203-B16-01 Study Design: A randomized, open-label, rater-blinded, multicenter, 2-treatment, 2-period, multiple-dose crossover study. Approximately 30 qualified IR CD-LD-experienced advanced PD subjects will be randomized. The study duration will be approximately 8 weeks, including the screening period.

Official Title
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A Randomized, Multiple Dose Study to Assess the Pharmacokinetics and Pharmacodynamics of IPX203 in Subjects With Advanced Parkinson's Disease

Conditions
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Advanced Parkinson's Disease

Intervention / Treatment
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* Drug: Sinemet
* Drug: IPX203


Participation Criteria
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Eligibility Criteria
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Eligibility will be determined at screening and Visit 1 of the study. Inclusion Criteria: Diagnosed with idiopathic PD at age ≥ 40 years who are being chronically treated with stable regimens of CD-LD but experiencing motor complications. Hoehn and Yahr Stages 2, 3, or 4 Montreal Cognitive Assessment (MoCA) score ≥ 24 at Screening Visit in on state. For the 4 weeks prior to the Screening, the subject experiences daily wearing-off episodes with periods of bradykinesia and rigidity and experiences an off state upon awakening on most mornings by history. Responsive to CD-LD therapy and currently being treated on a stable regimen with CD-LD for at least 4 weeks prior to Visit 1 Typically experiences an on response with the first dose of IR CD-LD of the day (by subject history). By history, efficacy of the first morning dose of IR CD-LD lasts less than 4 hours Exclusion Criteria: History of medical conditions or of a prior surgical procedure that would interfere with LD absorption, such as gastrectomy or proximal small-bowel resection. Liver enzyme values ≥ 2.5 x the upper limit of normal; or history of severe hepatic impairment. History of drug or alcohol abuse within the 12 months prior to Screening. Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: any doses of a controlled-release (CR) LD apart from a single daily bedtime dose or any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo). Received within 4 weeks of Visit 1 or planning to take during participation in the clinical study: nonselective monoamine oxidase (MAO) inhibitors, apomorphine, or dopaminergic blocking agents including antiemetics. History of psychosis within the past 10 years. Treatment with any dopamine antagonist antipsychotics for the purposes of psychosis or bipolar disorder within the last 2 years. Based on clinical assessment, subject does not adequately comprehend the terminology needed to complete the PD Diary.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 100 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPX203 then Sinemet<br>Participants first received IPX203 ER CD-LD Capsules for 15 days After a Washout Period of 7 days; participants then received Sinemet (IR CD-LD) Tablet for 15 days Study drug doses were determined based on the subject's prestudy IR CD-LD regimen The typical IPX203 dosing regimen was 3 times a day, dosed approximately every 7 to 8 hours. | Drug: Sinemet<br>* Immediate Release Tablet containing carbidopa-levodopa flexible dosing<br>* Other names: IR CD-LD Tablets;Drug: IPX203<br>* Extended Release capsules containing carbidopa-levodopa flexible dosing<br>* Other names: IPX203 ER CD-LD Capsules;|
| Experimental: Sinemet then IPX203<br>Participants first received Sinemet Capsules for 15 days After a Washout Period of 7 days; participants then received IPX203 ER CD-LD Capsules for 15 days Study drug doses were determined based on the subject's prestudy IR CD-LD regimen The typical IPX203 dosing regimen was 3 times a day, dosed approximately every 7 to 8 hours. | Drug: Sinemet<br>* Immediate Release Tablet containing carbidopa-levodopa flexible dosing<br>* Other names: IR CD-LD Tablets;Drug: IPX203<br>* Extended Release capsules containing carbidopa-levodopa flexible dosing<br>* Other names: IPX203 ER CD-LD Capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levodopa Cmax Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Levodopa Tmax Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Levodopa t1/2 Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Levodopa AUCt Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Levodopa AUCinf Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Levodopa Bioavailability Relative to IR CD/LD Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Carbidopa Cmax Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Carbidopa Tmax Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Carbidopa t1/2 Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Carbidopa AUCt Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Carbidopa AUCinf Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Carbidopa Bioavailability Relative to IR CD/LD Following First Dose on Day 1 | Single Dose predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 5.5, 6, 6.5, 7, 7.5, and 8 hours postdose | Day 1 | 
| Levodopa Cmax Following First Dose on Day 15 | Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. | Day 15 | 
| Levodopa Tmax Following First Dose on Day 15 | Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. | Day 15 | 
| Levodopa AUCtau Following First Dose on Day 15 | Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. | Day 15 | 
| Carbidopa Cmax Following First Dose on Day 15 | Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. | Day 15 | 
| Carbidopa Tmax Following First Dose on Day 15 | Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. | Day 15 | 
| Carbidopa AUCtau Following First Dose on Day 15 | Multiple Dose predose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, and 10 hours postdose. | Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IPX203 (carbidopa-levodopa) Extended-Release capsules