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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Parkinson's Disease
• Intervention / Treatment: Drug: Sinemet; Drug: IPX203

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Investigator 110
    • Little Rock, Arkansas, United States, 72205
      • Site 114
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Investigator 106
    • Naples, Florida, United States, 34102
      • Investigator 112
    • Port Charlotte, Florida, United States, 33980
      • Investigator 113
    • Tampa, Florida, United States, 33613
      • Site 108
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Investigator 101
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Site 103
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Investigator 109
  • Washington
    • Kirkland, Washington, United States, 98034
      • Site 115
    • Spokane, Washington, United States, 99202
      • Investigator 104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: IR CD-LD Tablets; Drug: IPX203; Extended Release capsules containing carbidopa-levodopa flexible dosing; Other Names: 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 Names: IR CD-LD Tablets; Drug: IPX203; Extended Release capsules containing carbidopa-levodopa flexible dosing; Other Names: IPX203 ER CD-LD Capsules

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Impax Laboratories, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2016
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: December 28, 2016
• First Posted (Estimate): January 2, 2017

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: IPX203 (carbidopa-levodopa) Extended-Release capsules
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Carbidopa, levodopa drug combination
• Other Study ID Numbers: IPX203-B16-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No