An evaluation on the long-term treatment profile of sodium oxybate on pediatrics with narcolepsy revealed a safety profile similar to previous adult studies and identified no unexpected safety concerns.
In a recently published phase 3, double-blind, randomized withdrawal study (NCT02221869) in the Journal of Clinical Sleep Medicine, sodium oxybate demonstrated long-term maintenance of efficacy in pediatric patients with narcolepsy and cataplexy.1 These findings provide additional and critical information about the effectiveness of this therapy in a pediatric population.
In sodium oxybate-naive participants and patients previously treated with the medication, efficacy prior to the withdrawal period was maintained throughout the open label period (OLP) for number of weekly cataplexy attacks. The median change in number of these attacks from the stable-dose period to end of the OLP was 0.0 [quartile 1: −2.5; quartile 3: 4.9] and 0.0 [quartile 1: −3.4;quartile 3: 2.6), respectively, among oxybate-naïve patients and those previously on the therapy. Additionally, Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) scores were maintained among these 2 groups as well(sodium oxybate-naïve: median, 0.0 [quartile 1: −3.0; quartile 3: 2.5] and previously taken group: median, 1.0 [quartile 1: −3.0; quartile 3: 3.0]).
Lead author Michel Lecendreux, MD, sleep medicine specialist, Robert Debré Hospital, Paris, France, and colleagues wrote that, “on long-term treatment effects of [sodium oxybate] on cataplexy and EDS in children and adolescents with narcolepsy with cataplexy, a chronic disorder, complement the previously published main findings of this trial.”1,2
This multicenter study of 30 sites in 5 countries had a trial duration of up to 1 year. Among 106 participants enrolled between October 2014 and November 2016, 95 entered and only 85 completed the OLP. Participants were children and adolescents between 7 and 16 years of age who were diagnosed with narcolepsy with cataplexy. In addition, the patients required a history of at least 14 cataplexy attacks in a 2-week period and clinically significant EDS prior to treatment.
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Treatment-naive patients were titrated to a dose of sodium oxybate and sodium oxybate-treated participants were entered on their established dose. After a stable dose 2-week period and 2-week withdrawal period, patients were entered into an OLP less than or 47 weeks. During the OLP, measurements for efficacy included the number of weekly cataplexy attacks, cataplexy-free days, and ESS-CHAD. Additionally, safety outcomes treatment-emergent adverse events (TEAEs) were observed including assessments of mental health such as depression and polysomnography.
During the withdrawal period, the average number of cataplexy-free days per week reduced to 0.0 (quartile 1, 0.0; quartile 3, 2.6) in patients randomly assigned to placebo (n = 32). In contrast, the number of cataplexy-free days was stable at 4.0 (quartile 1, 1.0; quartile 3, 6.0) in patients who continued the treatment (n = 31). Notably, the number of cataplexy-free days per week remained stable during the OLP.
The average number of cataplexy-free days per week was 2.3 (quartile 1, 0.0; quartile 3, 6.0) in the first week of the OLP and 3.8 (quartile 1, 0.5; quartile 3, 5.5) in week 48. During the last week in the OLP, the median number of cataplexy-free days observed was 4.7 (quartile 1, 0.0; quartile 3, 7.0) in the overall population (n = 94) compared with4.7 (quartile 1, 0.0; quartile 3, 7.0) in treatment naive patients at the study entry (n = 62), and 5.0 (quartile 1, 0.0; quartile 3, 7.0) in patients taking sodium oxybate at study entry (n = 32).
There were 2 patients who did not take any dose of study drug. Among the 104 participants that received at least 1 dose of sodium oxybate, 80 (76.9%) patients reported TEAEs during all study periods. The majority of the TEAEs in patients were mild or moderate in severity (7-11 years of age: 78.4%, 7–11; 12-17 years of age: 76.1%).
TEAEs were reported more frequently with sodium oxybate-naive compared with those taking the treatment at study entry (83.3% and 62.5%, respectively). The TEAEs most frequently reported (at least 5%) were enuresis (19.2%), nausea (19.2%), vomiting (18.3%), headache (17.3%), decreased weight (11.5%), decreased appetite (8.7%), nasopharyngitis (7.7%), upper respiratory tract infection (5.8%), and dizziness (7.7%).
“A limitation of the study is the smaller sample size in the 7- to 11-year-old age group relative to the 12-to 17-year-old age group,” Lecendreux et al noted.1