A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic Hypersomnia

This is a double-blind, placebo-controlled, randomized withdrawal study in adult participants (ages ≥18 years) with IH. The study will consist of a Screening Period (up to 28 days), an 8-week Open-Label Phase, and a 4-week Double-Blind Randomized Withdrawal Phase. The Open-Label Phase of the study will be 8 weeks, which includes a 6-week Dose Optimization Period and a 2-week Stable Dose Period. In the Dose Optimization Period, all participants will be titrated to their optimal dose of open-label pitolisant (17.8 milligrams \[mg\] or 35.6 mg) based on Investigator assessment of tolerability and efficacy. The 3-week titration period will be followed by 3 weeks of flexible dosing (weeks 4-6) during which participants will continue to receive their optimal dose of 17.8 mg or 35.6 mg open-label pitolisant. Participants taking a strong cytochrome P450 2D6 (CYP2D6) inhibitor will be allowed in the study; however, for these participants, the maximum permitted daily dose of pitolisant will be 17.8 mg. Following completion of the 6-week Dose Optimization Period, participants will enter the 2-week Stable Dose Period. During this period, participants will remain at their optimal dose (the same dose they were taking at the end of the Dose Optimization Period \[17.8 mg or 35.6 mg\]) of open-label pitolisant for 2 weeks; dose adjustments are not allowed during the Stable Dose Period. At the end of the Stable Dose Period, participants will be defined as responders or non-responders. Responders will be randomized in a 1:1 ratio to receive blinded study drug (pitolisant or matching placebo) in the Double-Blind Randomized Withdrawal Phase of the study. Non-responders will not be randomized to treatment in the Double-Blind Randomized Withdrawal Phase and will complete two safety follow-up telephone contacts (TCs) at 15 (±3) days and 30 (+3) days after their final dose of open-label pitolisant. During the Double-Blind Randomized Withdrawal Phase, participants (approximately 64 participants per treatment group) will receive blinded study drug either at the same dose they were taking in the Stable Dose Period (17.8 mg or 35.6 mg pitolisant) or matching placebo. The duration of the Double-Blind Randomized Withdrawal Phase will be 4 weeks (weeks 9-12); dose adjustments are not permitted during this phase of the study. After completion of the Double-Blind Randomized Withdrawal Phase (End-of Treatment Visit is on Day 84, the last day of blinded treatment), participants will complete two safety follow-up TCs with the site at 15 (±3) days and 30 (+3) days after their final dose of blinded study drug, which will include assessment for adverse events and concomitant medication use; alternatively, participants will have the opportunity to enroll in a long-term, open-label safety study under a separate protocol. Participants who opt to enroll into the long-term, open-label study will not complete the 15-day and 30-day follow-up TCs.