A Phase 2a, Double-blind, Placebo-controlled Study of ORX750 in Patients with Narcolepsy (type 1 and 2) and Idiopathic Hypersomnia: Study Design
Recommended Citation
Dauvilliers Y, Plazzi G, Plante D, Mignot E, Roth T, Sterkel A, Hartman D, Kong J, Accardi M, Saha S, Im E. A Phase 2a, Double-blind, Placebo-controlled Study of ORX750 in Patients with Narcolepsy (type 1 and 2) and Idiopathic Hypersomnia: Study Design. Sleep 2025; 48:A373-A374.
Document Type
Conference Proceeding
Publication Date
5-19-2025
Publication Title
Sleep
Abstract
Introduction: Narcolepsy types 1 (NT1) and 2 (NT2), and idio pathic hypersomnia (IH) are rare, debilitating central disorders of hypersomnolence characterized by excessive daytime sleepi ness (EDS). None of the currently available therapies target the orexin system, which is a core element of wake-promoting cir cuitries and specifically, of NT1 pathology. ORX750 is a novel, investigational oral orexin-2 receptor (OX2R) agonist that demonstrated strong wake-promoting effects in acutely sleep-de prived healthy volunteers (ongoing phase 1 study). An ongoing phase 2a study, ORX750-0201 will evaluate the safety, tolerabil ity, efficacy, and PK of ORX750 in NT1, NT2, and IH patients. Methods: This phase 2a study is a randomized, double-blind, placebo-controlled, cross-over basket study with separate cohorts for NT1, NT2, and IH. Initial dosing will be 1 mg (NT1) and 2 mg (NT2 and IH) with sequential dose escalation/ de-escalation between cohorts. Within dosing cohorts, par ticipants will be randomized to one of two blinded treatment sequences and receive ORX750 for 4 weeks and placebo for 2 weeks (6-week treatment duration total) in a crossover design. Efficacy endpoints will include the Maintenance of Wakefulness Test (MWT), Epworth Sleepiness Scale (ESS), and weekly cat aplexy rate (NT1 only). Other exploratory assessments include measures of overall symptom improvement, sleep, cognition, attention, memory, and general health. Results: This study plans to complete 78 participants (n=18 NT1; n=24 NT2; n=36 IH), with three dose cohorts per disorder. This 6-week crossover study has >87.5 % power within each dos ing cohort to detect a 15 min change in mean sleep latency on the MWT relative to placebo (two-sided α=0.05). The study initiated with participating sites in the US, Canada, and EU. Data for all three disorders are expected in 2025. Conclusion: This study will evaluate the safety, tolerability, effi cacy, and PK of multiple doses of ORX750 for the first time in patients with NT1, NT2, and IH with results informing future clinical studies.
Volume
48
First Page
A373
Last Page
A374
