0655 Novel Design Elements to Evaluate Sleep Architecture and Outcomes in an Idiopathic Hypersomnia and Narcolepsy Study

Abstract Introduction Although the efficacy and safety of low-sodium oxybate (LXB, Xywav®) in the treatment of idiopathic hypersomnia and narcolepsy are well established, opportunities remain to better understand its impact on sleep architecture and other daytime/nighttime outcomes important to patients and clinicians. Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) is a phase 4, prospective, multicenter, single-arm, open-label interventional study designed with novel methodology and expert input to evaluate the impact of LXB on excessive daytime sleepiness, polysomnographic (PSG) sleep parameters, and functional outcomes in adults with idiopathic hypersomnia or narcolepsy (type 1 or 2). Methods DUET includes a screening period (with a 2-week washout for participants taking oxybate at study entry), 1-week baseline period (off-treatment), 2- to 8-week titration period (for flexible LXB dosing adjustments based on participants’ needs), 2-week stable-dose period, 1- to 2-week end-of-treatment period (on LXB), and safety follow-up (after 2 weeks). To more comprehensively understand the impact of LXB on sleep architecture and other daytime/nighttime outcomes, novel design elements were integrated into the study. Input from an expert advisory board helped refine the study design and ensure that the most relevant elements for patients and clinicians were incorporated into the final DUET protocol. Responses from a premeeting survey of advisors focused on eligibility criteria, suitability of endpoints, newly created questionnaires, and analyses and were discussed during a 4-hour workshop with the study sponsor. Results Advisors were 6 clinicians with expertise in treating patients with idiopathic hypersomnia and narcolepsy and/or with expertise in PSG. Novel design aspects discussed and incorporated into the protocol included PSG conducted with ad libitum sleep duration, objective evaluation of sleep inertia using the Psychomotor Vigilance Test, a new questionnaire for capturing clinician-reported dosing to better understand dosing rationale, evaluation of motor activity during sleep (with PSG), and evaluation of dysautonomia using the Orthostatic Hypotension Questionnaire. Conclusion DUET is the first prospective evaluation of the impact of LXB on sleep architecture (PSG) in patients with idiopathic hypersomnia or narcolepsy. Results from these novel elements will provide patients and clinicians with additional information regarding the impact of LXB on nighttime/daytime symptomatology. Support (if any) Jazz Pharmaceuticals