Patient Dosing Begins for Phase 3 Study of Once-Nightly Sodium Oxybate in Idiopathic Hypersomnia

Richard Bogan, MD, FCCP, FAASM

Avadel Pharmaceuticals has announced that the first patient has been dosed in its phase 3 study, dubbed REVITALYZ (NCT06525077), which assesses the efficacy and safety of once-nightly sodium oxybate (Lumryz) as a potential treatment for idiopathic hypersomnia (IH).¹

The double-blind, placebo-controlled, randomized withdrawal, multicenter study is expected to enroll 150 patients with IH who will be randomized to once-nightly sodium oxybate or placebo. The estimated total duration of study for each subject is approximately 42 weeks, including the open-label safety extension period, although the study’s primary end point will be assessed at 14 weeks. Investigators will specifically look to see whether the treatment can reduce daytime sleepiness, as measured by total score on the Epworth Sleepiness Scale (ESS).

"IH is a debilitating sleep disorder characterized by profound sleep inertia, or difficulty waking up and persistent profound daytime sleepiness. Awareness and diagnosis of IH has increased markedly over the last several years. However, IH patients are severely limited in effective treatment options, representing a large unmet need," study author Richard Bogan, MD, FCCP, FAASM, associate clinical professor at the University of South Carolina School of Medicine, said in a statement.¹ "The potential of LUMRYZ to treat IH with only a single bedtime dose of extended-release sodium oxybate is promising, and the initiation of the Phase 3 REVITALYZ study marks a significant step toward improving care for those living with IH."

The study includes those with IH, aged 18 to 75, who have a total ESS score greater than 11 at screening and an average nightly total sleep time of more than 7 hours. Patients in the study may use stimulants/alerting agents but dose and regimen must be stable for 2 months prior to screening, and remain stable until the double-blind, randomized withdrawal visit. Females of childbearing potential must use highly effective contraception for 2 months prior to baseline, throughout the study, and for 30 days after the last dose of study drug.

In terms of exclusion, pregnant, nursing, or lactating females are not allowed to participate in the trial. In addition, the study excludes those with hypersomnia due to another medical, behavioral, sleep, or psychiatric condition, as well as those with untreated or incompletely treated sleep apnea who have apnea-hypopnea index scores greater than 15. Those with clinically significant parasomnias, a history or presence of seizures, head trauma, succinic semialdehyde dehydrogenase are also excluded from the trial.

RIVATALYZ enrollment is open for both participants switching from immediate-release oxybates and not currently taking oxybates. In addition to observing change on ESS, the study will also evaluate other secondary end points, including patient and clinician impression of change, idiopathic hypersomnia severity, and a measure of the functional outcomes of sleep.

Jennifer Gudeman, PharmD

"Dosing the first patient in REVITALYZ is an important milestone for the IH community, which has been vocal in the need for more treatment options, particularly an extended-release form of oxybate that would ideally provide full nocturnal drug exposure in a single, once-at-bedtime dose," Jennifer Gudeman, PharmD, senior vice president of Medical and Clinical Affairs at Avadel, said in a statement. "We are committed to advancing this study and are emboldened by the excitement of experienced clinical trial sites’ participation, which reflects the critical unmet need in the current therapeutic landscape."

There is currently only 1 FDA-approved treatment for IH, which is Jazz Pharmaceuticals’ JZP-258, a combination agent of calcium, magnesium, potassium, and sodium oxybates.² Avadel’s sodium oxybate, formerly known as FT218, was approved as a treatment for cataplexy or excessive daytime sleepiness in adults with narcolepsy in May 2023. With its approval, it became the first and only marketed once-nightly oxybate for patients with the condition.³

Lumryz comes with a boxed warning as a central nervous system depressant, and for its potential abuse and misuse. It is currently only available through a restricted program under a Risk Evaluation and Mitigation Strategy called the Lumryz REMS. With the approval, the drug was granted 7 years of orphan drug exclusivity.

REFERENCES
1. 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 August 2, 2024. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-first-patient-dosed-phase-3
2. Jazz Pharmaceuticals Announces U.S. FDA Approval of Xywav® (calcium, magnesium, potassium, and sodium oxybates) Oral Solution for Idiopathic Hypersomnia in Adults. News release. Jazz Pharmaceuticals. August 12, 2021. Accessed August 2, 2024. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-approval-of-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-for-idiopathic-hypersomnia-in-adults-301354616.html
3. 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 August 2, 2024. 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