Phase 3b Open-Label Randomized Study of IPX203 Versus Immediate-Release Levodopa/Carbidopa in Advanced Parkinson's Disease with Motor Fluctuations

The primary objective is to evaluate the efficacy of IPX203 in comparison to an immediate-release levodopa and aromatic L-amino acid decarboxylase inhibitor regimen regarding the improvement of ON time in relation to dosing interval and frequency in patients with advanced Parkinson’s disease experiencing motor fluctuations. Secondary objectives include:

• Investigation of efficacy in reducing OFF time relative to dosing interval and frequency.
• Assessment of efficacy in increasing overall ON time, including instances with or without dyskinesia.
• Evaluation of efficacy using validated questionnaires.
• Investigation of safety associated with different dosing frequencies of IPX203 compared to the immediate-release regimen.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients aged 40 years or older diagnosed with Parkinson’s disease. Eligible participants must meet the United Kingdom Parkinson’s Disease Society Brain Bank Diagnostic Criteria and exhibit Hoehn and Yahr Stages 2.5 to 4 during the ON-state. Inclusion requires a history of daily predictable wearing-OFF episodes and an average of at least three cumulative hours of OFF time per day while awake. Participants must have been on a stable, optimized regimen of levodopa (LD) and an aromatic L-amino acid decarboxylase inhibitor (AAADI) for at least three months prior to screening. The required medication frequency is at least five LD doses per day, with a minimum total daily dose of 500 mg of LD/AAADI. If utilizing immediate-release or controlled-release formulations in combination with a COMT inhibitor, the dosing frequency must be between three and six times daily.

This Phase 3b, open-label, randomised study is designed to evaluate the efficacy of IPX203 in subjects with advanced Parkinson’s disease experiencing motor fluctuations. The research methodology compares IPX203 to an immediate-release levodopa and aromatic L-amino acid decarboxylase inhibitor regimen. The primary objective is to investigate changes in good ON time at Week 12 compared to baseline. Secondary endpoints include assessments of OFF time, dyskinesia, and various clinical outcome assessments. The study involves a screening period to ensure participants meet specific criteria, such as stable medication regimens and documented daily predictable wearing-OFF episodes. Participants will undergo follow-up assessments through Week 12 to monitor efficacy and clinical outcomes. The total duration of the trial is estimated to span from August 2025 to July 2028.

The experimental medication, IPX203 (H006629), consists of levodopa and carbidopa monohydrate. This substance is administered as a modified-release capsule, hard via oral use.

The comparator treatment is a combination of levodopa and benserazide hydrochloride, classified as a levodopa and decarboxylase inhibitor. This regimen is administered via oral use in a pharmaceutical form designated as PHF00006MIG.

The efficacy assessment focuses on subjects with advanced Parkinson’s disease experiencing motor fluctuations. The primary endpoint is the change in good ON time at Week 12 compared to baseline, evaluated for IPX203 against an immediate-release levodopa and aromatic L-amino acid decarboxylase inhibitor regimen. Specifically, this measurement compares durations greater than 1 hour and less than or equal to 1 hour.

Secondary efficacy parameters include:

• Change from baseline in OFF time at Week 12.
• Changes from baseline in ON time, ON time with dyskinesia, ON time with troublesome dyskinesia, ON time with non-troublesome dyskinesia, and ON time without dyskinesia, all measured up to Visit 5 via a Parkinson’s disease diary.
• Changes from baseline in clinical outcome assessments as specified in the protocol.