Efficacy, Safety, and Tolerability of BRP-185 (Bupropion immediate-release (IR) and sustained-release (SR)) in Adults with Idiopathic Hypersomnia

This is a Phase 2b, randomized, double-blind, placebo-controlled, multicentre trial evaluating two dose levels of BRP-185 against placebo in adult patients diagnosed with idiopathic hypersomnia. BRP-185 is a combination of Bupropion immediate-release (IR) and sustained-release (SR) formulations. There are 2 treatment groups: 1. High-dose BRP-185 group (225 mg - 75 mg Bupropion IR + 150 mg Bupropion SR) – oral capsule once daily in the morning 2. Low-dose BRP-185 group (150 mg - 75 mg Bupropion IR + 75 mg Bupropion SR) – oral capsule once daily in the morning The study is structured into three distinct phases: the screening phase, the treatment phase, and the follow-up phase, each designed to ensure accurate diagnosis, appropriate treatment administration, and comprehensive safety monitoring. The screening phase lasts up to 28 days and serves to confirm eligibility based on the International Classification of Sleep Disorders, Third Edition (ICSD-3) criteria for Idiopathic Hypersomnia (IH). Participants undergo comprehensive medical evaluations, including a detailed clinical history, physical examination, and objective sleep assessments. Baseline sleep data is obtained using actigraphy and sleep logs, with polysomnography (PSG) performed if necessary to rule out other sleep disorders. If participants have been using wake-promoting agents before enrollment, they are required to undergo a washout period to eliminate residual pharmacological effects that may confound baseline assessments. Once eligibility is confirmed, participants proceed to randomization. The treatment phase spans 12 weeks, during which participants receive once-daily morning doses of their assigned treatment. Throughout this period, participants attend scheduled clinic visits at Weeks 2, 4, 8, and 12, during which assessments such as the Epworth Sleepiness Scale (ESS), sleep inertia severity, and functional tests are performed. Cognitive neuropsychological tests, and sleep patterns are assessed through actigraphy and sleep diaries. Safety monitoring is conducted at all study visits, with adverse event tracking, laboratory tests, electrocardiograms (ECG), and vital sign assessments. Participants also complete patient-reported outcome measures, including the Patient Global Impression of Change (PGIC) scale. The follow-up phase lasts for two weeks following the completion of the treatment phase. Participants return for a final clinical assessment, during which vital signs, laboratory parameters, and ECG findings are reviewed. Adherence strategies to assess compliance include study drug compliance monitoring via the study app, return of unused Investigational Product (IP) during clinic visits for reconciliation.