Effect of sodium oxybate on body mass index in pediatric patients with narcolepsy

We examined body mass index (BMI) changes associated with sodium oxybate treatment (SXB) in pediatric patients with narcolepsy with cataplexy who participated in a double-blind, placebo-controlled, randomized withdrawal study and an open-label continuation period.

Participants were aged 7–16 years at screening. SXB-naive participants titrated to twice-nightly dosing of SXB then entered a 2-week stable-dose period; participants taking SXB at study entry entered a 3-week stable-dose period. After a 2-week randomized withdrawal period, all participants entered an open-label safety period (OLP; main study duration: ≤ 52 weeks). Participants who completed the OLP were allowed to enter the open-label continuation period (an additional 1–2 years). BMI percentile categories were defined as underweight (< 5th), normal (5th to < 85th), overweight (≥ 85th to < 95th), and obese (≥ 95th).

Median BMI percentile decreased from baseline to OLP week 52 in SXB-naive participants who were normal weight at baseline (decreased from 77.0 to 35.0) or overweight/obese at baseline (98.0 to 86.7). Median BMI percentile decreased to a lesser extent in participants taking twice-nightly SXB at study entry who were normal weight at baseline (54.6 to 53.0) or overweight/obese at baseline (96.5 to 88.9). Shifts in BMI category from baseline to week 52 were sometimes noted. In SXB-naive participants, 9/10 (90.0%) who were overweight became normal weight, 7/25 (28.0%) who were obese became normal weight, 3/25 (12.0%) who were obese became overweight, and 1/16 (6.3%) who was normal weight became obese. In participants taking SXB at baseline, 5/8 (62.5%) who were overweight became normal weight, 3/6 (50.0%) who were obese became overweight, 1/14 (7.1%) who was normal weight became overweight, and 2/14 (14.3%) who were normal weight became underweight. Median BMI percentiles at months 6 and 12 of the open-label continuation period were similar to those at OLP end (OLP week 52). In SXB-naive participants, the evident BMI z-score decrease over time was relative to the screening values.

Decreases in BMI percentile and z-score, and downward shifts in BMI category, were observed within 1 year of SXB treatment in pediatric participants with narcolepsy with cataplexy. BMI decreases plateaued after approximately 1 year.

Registry: ClinicalTrials.gov; Name: A Multicenter Study of the Efficacy and Safety of Xyrem With an Open-Label Pharmacokinetic Evaluation and Safety Extension in Pediatric Subjects With Narcolepsy With Cataplexy; URL: https://clinicaltrials.gov/study/NCT02221869; Identifier: NCT02221869.