A Study to Assess the PK and Pharmacodynamics of IPX203 in Subjects With Advanced Parkinson's Disease
- Registration Number
- NCT03007888
- Lead Sponsor
- Impax Laboratories, LLC
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sinemet then IPX203 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. IPX203 then Sinemet IPX203 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. IPX203 then Sinemet 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. Sinemet then IPX203 Sinemet 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.
- Primary Outcome Measures
Name Time Method Levodopa Cmax Following First Dose on Day 1 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
Levodopa Tmax Following First Dose on Day 1 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
Levodopa t1/2 Following First Dose on Day 1 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
Levodopa AUCt Following First Dose on Day 1 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
Levodopa AUCinf Following First Dose on Day 1 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
Levodopa Bioavailability Relative to IR CD/LD Following First Dose on Day 1 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
Carbidopa Cmax Following First Dose on Day 1 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
Carbidopa Tmax Following First Dose on Day 1 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
Carbidopa t1/2 Following First Dose on Day 1 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
Carbidopa AUCt Following First Dose on Day 1 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
Carbidopa AUCinf Following First Dose on Day 1 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
Carbidopa Bioavailability Relative to IR CD/LD Following First Dose on Day 1 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
Levodopa Cmax Following First Dose on Day 15 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.
Levodopa Tmax Following First Dose on Day 15 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.
Levodopa AUCtau Following First Dose on Day 15 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.
Carbidopa Cmax Following First Dose on Day 15 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.
Carbidopa Tmax Following First Dose on Day 15 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.
Carbidopa AUCtau Following First Dose on Day 15 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (11)
Site 114
🇺🇸Little Rock, Arkansas, United States
Investigator 109
🇺🇸Cleveland, Ohio, United States
Investigator 104
🇺🇸Spokane, Washington, United States
Site 103
🇺🇸Durham, North Carolina, United States
Investigator 112
🇺🇸Naples, Florida, United States
Investigator 113
🇺🇸Port Charlotte, Florida, United States
Site 108
🇺🇸Tampa, Florida, United States
Investigator 110
🇺🇸Little Rock, Arkansas, United States
Investigator 101
🇺🇸Farmington Hills, Michigan, United States
Investigator 106
🇺🇸Boca Raton, Florida, United States
Site 115
🇺🇸Kirkland, Washington, United States