REFRESH Study to Test Real-World Clinical Effectiveness of Once-Nightly Sodium Oxybate

Jennifer Gudeman, PharmD

At the 2025 SLEEP Annual Meeting, held June 8-11 in Seattle, Washington, investigators presented the design of a new multicenter observational study dubbed REFRESH, which will test the effectiveness, satisfaction, and safety of once-nightly sodium oxybate (Lumyrz; Avadel Pharmaceuticals), an FDA-approved treatment for narcolepsy.¹

The trial, which began recruitment in July 2024, is expected to include 60 participants aged at least 18 years with a confirmed diagnosis of narcolepsy type 1 or 2. Spanning across a number of centers, REFRESH will include individuals who are oxybate naïve or switching from twice-nightly sodium oxybate, another approved formulation of the drug. Patients with prior or current use of once-nightly sodium oxybate, presence of a clinical or mental health contraindication by the drug’s label, or have a mental or physical condition deemed exclusionary by the study clinician will be unable to participate in the trial.

Led by many study authors, including Jennifer Gudeman, PharmD, senior vice president of Medical and Clinical Affairs at Avadel, REFRESH collects various data across 4 monthly clinic visits, while patients are asked to complete self-assessments throughout that time. The main scales and assessments used include the Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale symptom scores, Sheehan Disability Scale, Patient and Clinician Global Impression of Change. The study will also test vital signs, including changes in blood pressure.

For those switching from twice-nightly to once-nightly treatment, these patients will be retrospectively asked how often they missed doses, how missed doses affect their narcolepsy symptoms and function, and if twice-nightly dosing regimen of sodium oxybate was associated with safety concerns. A unique twist to the study, partners of switch participants may participate to understand how twice-nightly dosing affected them. Overall, the goal of REFRESH is to understand more about the real-world experiences with once-nightly sodium oxybate, as well as gain insights for decision-making between twice-nightly and once-nightly solutions.

READ MORE: Samelisant Significantly Reduces Excessive Daytime Sleepiness in Phase 2 Narcolepsy Study

Once-nightly sodium oxybate, the first and only FDA-approved once-nightly oxybate treatment for those with narcolepsy, gained FDA approval in 2023 to treat excessive daytime sleepiness and cataplexy in those living with the condition.² Lumyrz, its market name, comes with a boxed warning for its potential abuse and misuse and thus, is prescribed through a Risk Evaluation and Mitigation Strategy (REMS) program. Originally approved for adults with narcolepsy, the once-nightly formulation had its indication expanded in late 2024 to include patients 7 years of age and older with the condition.³

Investigators have been uncovering data on patients’ preference of once-nightly vs twice-nightly for years through the open-label RESTORE trial (NCT04451668). Data from this study, published in SLEEP Medicine: X in 2024, revealed that 93.9% (92 of 98) of patients who completed a preference questionnaire preferred once-nightly over twice-nightly. At baseline, 69.2% reported missing their second immediate-release oxybate dose at least once; in these cases, 80% felt worse the next day.⁴

Additional data from the RESTORE study showed that about 39% of patients took a second dose of immediate-release oxybate at least 4 hours after the first, with over half (51%) reporting feeling somewhat to extremely groggy or unsteady the next morning. Most (92%) got out of bed after the second dose, and among them, 8% experienced falls and 4% reported injuries. Among those who switched and completed the end-of-study survey, 91.2% felt better able to follow the once-nightly sodium oxybate (ON-SXB) dosing schedule.

Once-nightly sodium oxybate is also being tested as a treatment for patients with idiopathic hypersomnia (IH) through the ongoing phase 3 REVITALYZ trial (NCT06525077). This double-blind, placebo-controlled, randomized withdrawal, multicenter study, which began dosing in August 2024, is expected to have 150 patients with IH who will be randomized to once-nightly sodium oxybate or placebo for a total duration of 42 weeks. Change in ESS total score, the primary end point, will be observed at 14 weeks.⁵

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REFERENCES
1. Meskill S, Meskill G, Herpel L, et al. REFRESH: PROSPECTIVE, OBSERVATIONAL STUDY DESIGN OF ONCE-NIGHTLY SODIUM OXYBATE FOR NARCOLEPSY IN CLINICAL PRACTICE. Presented at: 2025 SLEEP Annual Meeting; June 8-11; Seattle, Washington. ABSTRACT 0857.
2. Avadel Pharmaceuticals announces final FDA approval of Lumryz (sodium oxybate) for extended-release oral suspension as the first and only once-at-bedtime oxybate for cataplexy or excessive daytime sleepiness in adults with narcolepsy. News release. Avadel Pharmaceuticals. May 1, 2023. Accessed June 8, 2025. https://www.globenewswire.com/news-release/2023/05/01/2658536/0/en/Avadel-Pharmaceuticals-Announces-Final-FDA-Approval-of-LUMRYZ-sodium-oxybate-for-Extended-Release-Oral-Suspension-as-the-First-and-Only-Once-at-Bedtime-Oxybate-for-Cataplexy-or-Exc.html
3. Avadel Pharmaceuticals Announces FDA Approval of LUMRYZ™ (sodium oxybate) Extended-Release Oral Suspension (CIII) for the Treatment of Cataplexy or Excessive Daytime Sleepiness in Patients 7 Years of Age and Older with Narcolepsy. News release. Avadel Pharmaceuticals. October 17, 2024. Accessed June 8, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-fda-approval-lumryztm-sodium
4. Roy A, Stern T, Harsh J, et al. RESTORE: Once-nightly oxybate dosing preference and nocturnal experience with twice-nightly oxybates. Sleep Med X. 2024;8:100122. doi:10.1016/j.sleepx.2024.100122
5. Avadel Pharmaceuticals Announces First Patient Dosed in Phase 3 REVITALYZ™ Trial of LUMRYZ™ (sodium oxybate) Extended-Release Oral Suspension for the Treatment of Idiopathic Hypersomnia. July 31, 2024. Accessed June 8, 2025. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-first-patient-dosed-phase-3