Once-Nightly Oxybate Demonstrates Safety in Narcolepsy Post-Hoc Study

Long-term use of extended-release, once-nightly sodium oxybate (ON-SXB) is well-tolerated among patients with narcolepsy type 1 or 2 (NT1/NT2), according to study results presented at the 2025 Annual Meeting of the American Academy of Sleep Medicine and the Sleep Research Society, held from June 7 to 11 in Seattle, Washington.

In the phase 3 clinical trial REST-ON (ClinicalTrials.gov Identifier: NCT02720744), researchers found that extended-release ON-SXB had a safety profile consistent with oxybate and the primary safety signal was related with tolerability.

In the long-term, open-label/switch trial RESTORE (ClinicalTrial.gov Identifier: NCT04451668), the researchers recruited patients (N=50) aged 16 years and older with NT1/NT2 after they completed the REST-ON trial. The patients either remained on 9 g ON-SXB per night or were initiated on 4.5 g ON-SXB per night and were titrated up by 1.5 g per week as needed until reaching the full dose after 1 or 2 months of titration. The patients continued ON-SXB until they could be transitioned to commercial therapy.

The primary outcomes of this safety analysis were treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs), defined as TEAEs considered to be drug related.

Participants (women or girls, 60%; mean age, 33 years; White, 80%) had an ON-SXB treatment duration of 408.1 (range, 8-1098) days. In REST-ON, 76% were oxybate-naïve.

Most participants (76%) experienced 1 or more TEAEs. Most TEAEs were mild (36%) or moderate (36%) in severity.

The most common TEAEs were nausea (26%), somnolence (12%), COVID-19 (12%), vomiting (10%), dizziness (10%), tremor (10%), and sinusitis (10%).

A single participant experienced a serious TEAE of anxiety and delusional thoughts considered related to ON-SXB. These events led to treatment discontinuation.

More than half of participants (56%) experienced ADRs.

The most common ADRs were nausea (24%), somnolence (12%), and dizziness (10%).

A total of 7 participants discontinued ON-SXB due to ADRs. The only safety signal leading to discontinuation in more than 1 participant (n=2) was nausea.

“These data from RESTORE demonstrate that REST-ON and oxybate-naive participants tolerated ON-SXB well, as TEAEs were primarily mild/moderate in severity. ADRs were aligned with the known safety profile of TN-SXB,” the researchers concluded.

Disclosure: This research was supported by Avadel Pharmaceuticals. Please see the original reference for a full list of disclosures