Incidence and duration of common, early-onset adverse events occurring during 2 randomized, placebo-controlled, phase 3 studies of sodium oxybate in participants with narcolepsy

Abstract

Study objectives: To determine the time course and duration of common, early-onset treatment-emergent adverse events (TEAEs) associated with sodium oxybate (SXB) use in adults with narcolepsy.

Methods: These were post hoc analyses of two 8-week, randomized, double-blind, placebo-controlled trials. In SXB-15, participants (n = 246) received daily placebo (n = 60) or SXB (n = 186) initiated at 4.5 g. Participants assigned to SXB 6 or 9 g were titrated in 1.5-g increments. In SXB-22, participants entering on modafinil (n = 231) received placebo (n = 56), SXB (n = 55), modafinil (n = 63), or SXB and modafinil (n = 57). SXB was initiated at 6 g for weeks 1-4 and increased to 9 g for weeks 5-8. TEAEs reported more frequently in SXB-treated participants than placebo and in ≥5% of any SXB treatment group during week 1 were examined as TEAEs of interest.

Results: Dizziness and nausea met criteria as TEAEs of interest in both studies; headache also met criteria as a TEAE of interest in SXB-15. Incidence of new or worsened TEAEs was highest at week 1 (SXB-15: dizziness, 7.5%; headache, 7.5%; nausea, 5.9%; SXB-22: dizziness, 5.4%; nausea, 7.1%) and decreased over time in both studies. The longest median duration was reported for dizziness: 9.0 and 17.5 days in SXB-15 and SXB-22, respectively. Dizziness caused discontinuation in 2.2% and 3.6% of participants in SXB-15 and SXB-22, respectively; nausea caused discontinuation in 2.7% and 1.8%.

Conclusions: Common early-onset TEAEs associated with SXB treatment were generally of short duration and their incidence decreased over time. These TEAEs accounted for few discontinuations overall.

Clinical trials registration: Registry: ClinicalTrials.gov; Names: Safety and Efficacy of Xyrem Oral Solution (Sodium Oxybate) Compared With Placebo in Narcoleptic Patients; Trial Comparing Effects of Xyrem Taken Orally and Modafinil With Placebo in Treating Daytime Sleepiness in Narcolepsy; URLs: https://ichgcp.net/clinical-trials-registry/NCT00049803 and https://ichgcp.net/clinical-trials-registry/NCT00066170; Identifiers: NCT00049803 and NCT00066170.

Keywords: dizziness; nausea; safety; sleepiness.

© 2020 American Academy of Sleep Medicine.

Figures

Figure 1. Incidence of new or worsened TEAEs of interest.

Horizontal bars indicate SXB titration steps for each of 3 SXB dose groups in SXB-15 (A) and all participants assigned to SXB in SXB-22 (B). TEAEs that occurred more frequently in participants treated with SXB than placebo and at an incidence ≥5% in any SXB treatment group during week 1 are shown for the all-treated populations. The double-blind treatment period in SXB-15 is up to week 8; week 9 reflects post–double-blind TEAE collection. SXB = sodium oxybate; TEAE = treatment-emergent adverse event.