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

NCT03007888 | Completed Phase 2 Results DMC

• 1 other identifier: IPX203-B16-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 11

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.

Conditions

Advanced Parkinson's Disease

Keywords

IPX203 (carbidopa-levodopa) Extended-Release capsules

Outcome Measures

Primary Outcomes (18)

• 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

Study Arms (2)

IPX203 then Sinemet

EXPERIMENTAL

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; Drug: IPX203

Sinemet then IPX203

EXPERIMENTAL

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; Drug: IPX203

Interventions

Sinemet DRUG

Immediate Release Tablet containing carbidopa-levodopa flexible dosing

Also known as: IR CD-LD Tablets

IPX203 then Sinemet; Sinemet then IPX203

IPX203 DRUG

Extended Release capsules containing carbidopa-levodopa flexible dosing

Also known as: IPX203 ER CD-LD Capsules

IPX203 then Sinemet; Sinemet then IPX203

Eligibility Criteria

• Age: 40 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Impax Laboratories, LLC: lead

Study Sites (11)

Investigator 110

Little Rock, Arkansas, 72205, United States

Location

Site 114

Little Rock, Arkansas, 72205, United States

Location

Investigator 106

Boca Raton, Florida, 33486, United States

Location

Investigator 112

Naples, Florida, 34102, United States

Location

Investigator 113

Port Charlotte, Florida, 33980, United States

Location

Site 108

Tampa, Florida, 33613, United States

Location

Investigator 101

Farmington Hills, Michigan, 48334, United States

Location

Site 103

Durham, North Carolina, 27705, United States

Location

Investigator 109

Cleveland, Ohio, 44106, United States

Location

Site 115

Kirkland, Washington, 98034, United States

Location

Investigator 104

Spokane, Washington, 99202, United States

Location

MeSH Terms

Interventions

carbidopa, levodopa drug combination

Results Point of Contact

• Title: Pamela Fitzpatrick, Director, Specialty Regulatory Affairs
• Organization: Impax Laboratories, LLC

pfitzpatrick@amneal.com

631-633-2104

Study Officials

• Impax Study Director

  Impax Laboratories, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: January 2, 2017
• Study Start: November 14, 2016
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: June 6, 2022
• Results First Posted: June 6, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)