P0311 - Effects of Sodium Oxybate on Body Mass Index in Pediatric Participants With Narcolepsy

Background/Purpose
Narcolepsy, a lifelong neurological sleep disorder with symptom onset frequently occurring during childhood or adolescence, is characterized by excessive daytime sleepiness (EDS), cataplexy (sudden loss of muscle tone usually triggered by emotions), sleep paralysis, sleep-related hallucinations, and disrupted nighttime sleep. Obesity is a common and burdensome comorbidity of pediatric narcolepsy. Sodium oxybate (SXB), a standard of care for cataplexy and EDS in narcolepsy, is approved in patients with narcolepsy 7 years and older. Body mass index (BMI) decreases have been observed with SXB treatment. We examined BMI changes by BMI percentile category at baseline in pediatric participants with narcolepsy.
Methods
Participants were aged 7–17 years with narcolepsy with cataplexy. SXB-naive participants were titrated to an optimal SXB dose, 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, placebo-controlled, double-blind, randomized-withdrawal period, all participants entered an open-label safety period (total study duration: ≤1 year). Weight categories were defined using BMI percentiles at baseline per Centers for Disease Control growth charts: underweight (<5th percentile), normal (≥5th to <85th percentile), overweight (≥85th to <95th percentile), and obese (≥95th percentile).
Results
Among SXB-naive participants, median (Q1,Q3) BMI percentile decreased with SXB treatment in participants categorized as normal weight and overweight/obese at baseline (normal weight, n=16: 76.5 [57.8,82.4] at baseline, 35.0 [20.5,62.6] at week 52; overweight/obese, n=35: 97.6 [93.6,99.1] at baseline, 86.7 [72.5,97.9] at week 52). Of participants normal weight at baseline, 15/16 (94%) remained normal weight at week 52 (Figure 1A). Of participants overweight at baseline, 9/10 (90%) were normal weight at week 52 (Figure 1B). Of participants obese at baseline, 15/25 (60%) remained obese, 3/25 (12%) became overweight, and 7/25 (28%) were at normal weight at week 52 (Figure 1C). Among participants taking SXB at study entry, BMI percentile decreased to a lesser degree (normal weight, n=14: 54.6 [28.9,74.0] at baseline, 53.0 [24.7,65.6] at week 52; overweight/obese, n=14: 94.5 [89.5,97.1] at baseline, 88.9 [82.4,94.8] at week 52). Of participants normal weight at baseline, 11/14 (79%) remained at normal weight while 2/14 (14%) became underweight at week 52 (Figure 2A). Of participants overweight at baseline, 5/8 (63%) were normal weight at week 52 (Figure 2B). Of participants obese at baseline, 3/6 (50%) remained obese and 3/6 (50%) were overweight at week 52 (Figure 2C). Decreased weight/weight loss was reported as an adverse event in 13 participants (11 SXB-naive; 1 participant withdrew). Four participants became underweight at any time during the study; all later returned to normal weight.
Conclusion
Decreases from obese to overweight or normal weight, and from overweight to normal weight, were observed with SXB treatment in pediatric participants with narcolepsy. Weight and BMI should be monitored during SXB treatment.