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

• ClinicalTrials.gov Identifier: NCT03007888
• Recruitment Status: Completed
• First Posted: January 2, 2017
• Results First Posted: June 6, 2022
• Last Update Posted: June 6, 2022
• Sponsor: Impax Laboratories, LLC
• Information provided by (Responsible Party): Impax Laboratories, LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Parkinson's Disease	Drug: Sinemet; Drug: IPX203	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multiple Dose Study to Assess the Pharmacokinetics and Pharmacodynamics of IPX203 in Subjects With Advanced Parkinson's Disease
• Actual Study Start Date: November 14, 2016
• Actual Primary Completion Date: August 1, 2017
• Actual Study Completion Date: August 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: IPX203 then Sinemet; 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; Immediate Release Tablet containing carbidopa-levodopa flexible dosing; Other Name: IR CD-LD Tablets; Drug: IPX203; Extended Release capsules containing carbidopa-levodopa flexible dosing; Other Name: IPX203 ER CD-LD Capsules
Experimental: Sinemet then IPX203; 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; Immediate Release Tablet containing carbidopa-levodopa flexible dosing; Other Name: IR CD-LD Tablets; Drug: IPX203; Extended Release capsules containing carbidopa-levodopa flexible dosing; Other Name: IPX203 ER CD-LD Capsules

Outcome Measures

Primary Outcome Measures :

1. Levodopa Cmax Following First Dose on Day 1 [ Time Frame: 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
2. Levodopa Tmax Following First Dose on Day 1 [ Time Frame: 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
3. Levodopa t1/2 Following First Dose on Day 1 [ Time Frame: 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
4. Levodopa AUCt Following First Dose on Day 1 [ Time Frame: 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
5. Levodopa AUCinf Following First Dose on Day 1 [ Time Frame: 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
6. Levodopa Bioavailability Relative to IR CD/LD Following First Dose on Day 1 [ Time Frame: 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
7. Carbidopa Cmax Following First Dose on Day 1 [ Time Frame: 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
8. Carbidopa Tmax Following First Dose on Day 1 [ Time Frame: 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
9. Carbidopa t1/2 Following First Dose on Day 1 [ Time Frame: 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
10. Carbidopa AUCt Following First Dose on Day 1 [ Time Frame: 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
11. Carbidopa AUCinf Following First Dose on Day 1 [ Time Frame: 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
12. Carbidopa Bioavailability Relative to IR CD/LD Following First Dose on Day 1 [ Time Frame: 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
13. Levodopa Cmax Following First Dose on Day 15 [ Time Frame: 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.
14. Levodopa Tmax Following First Dose on Day 15 [ Time Frame: 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.
15. Levodopa AUCtau Following First Dose on Day 15 [ Time Frame: 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.
16. Carbidopa Cmax Following First Dose on Day 15 [ Time Frame: 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.
17. Carbidopa Tmax Following First Dose on Day 15 [ Time Frame: 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.
18. Carbidopa AUCtau Following First Dose on Day 15 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arkansas

Investigator 110

Little Rock, Arkansas, United States, 72205

Site 114

Little Rock, Arkansas, United States, 72205

United States, Florida

Investigator 106

Boca Raton, Florida, United States, 33486

Investigator 112

Naples, Florida, United States, 34102

Investigator 113

Port Charlotte, Florida, United States, 33980

Site 108

Tampa, Florida, United States, 33613

United States, Michigan

Investigator 101

Farmington Hills, Michigan, United States, 48334

United States, North Carolina

Site 103

Durham, North Carolina, United States, 27705

United States, Ohio

Investigator 109

Cleveland, Ohio, United States, 44106

United States, Washington

Site 115

Kirkland, Washington, United States, 98034

Investigator 104

Spokane, Washington, United States, 99202

Sponsors and Collaborators

Impax Laboratories, LLC

Investigators

• Study Director: Impax Study Director; Impax Laboratories, LLC

  Study Documents (Full-Text)

Documents provided by Impax Laboratories, LLC:

Study Protocol  [PDF] October 5, 2016

Statistical Analysis Plan  [PDF] September 29, 2017

More Information

• Responsible Party: Impax Laboratories, LLC
• ClinicalTrials.gov Identifier: NCT03007888
• Other Study ID Numbers: IPX203-B16-01
• First Posted: January 2, 2017
• Results First Posted: June 6, 2022
• Last Update Posted: June 6, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Impax Laboratories, LLC:

IPX203 (carbidopa-levodopa) Extended-Release capsules

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Carbidopa, levodopa drug combination; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agonists; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action