The effectiveness of LUMRYZ in pediatric patients is based upon a clinical study in patients treated with immediate-release sodium oxybate, as described below.

The effectiveness of immediate-release sodium oxybate in the treatment of cataplexy or excessive daytime sleepiness in pediatric patients 7 years of age and older with narcolepsy was established in a double-blind, placebo-controlled, randomized-withdrawal study (NCT02221869). The study was conducted in 106 pediatric patients (median age: 12 years; range: 7 to 17 years) with a baseline history of at least 14 cataplexy attacks in a typical 2-week period prior to any treatment for narcolepsy symptoms. Of the 106 patients, 2 did not receive study drug and 63 patients were randomized 1:1 either to continued treatment with immediate-release sodium oxybate or to placebo. Randomization to placebo was stopped early as the efficacy criterion was met at the pre-planned interim analysis.

Patients entered the study either taking a stable dosage of immediate-release sodium oxybate or were immediate-release sodium oxybate-naïve. CNS stimulants were allowed at entry, and approximately 50% of patients continued taking a stable dose of stimulant throughout the stable-dose and double-blind periods. Immediate-release sodium oxybate-naïve patients were initiated and titrated based on body weight over a period of up to 10 weeks. The total nightly dose was administered in two divided doses, with the first dose given at nighttime and the second given 2.5 to 4 hours later. Once a stable dosage of immediate-release sodium oxybate had been achieved, these patients entered the 2-week stable-dose period; patients on a stable dosage of immediate-release sodium oxybate at study entry remained on this dosage for 3 weeks prior to randomization. Efficacy was established at dosages ranging from 3 g to 9 g of immediate-release sodium oxybate per night.

The primary efficacy measure was the change in frequency of cataplexy attacks. In addition, change in cataplexy severity was evaluated with the Clinical Global Impression of Change for cataplexy severity. The Clinical Global Impression of Change is evaluated on a 7-point scale, centered at No Change, and ranging from Very Much Worse to Very Much Improved. The efficacy of immediate-release sodium oxybate in the treatment of excessive daytime sleepiness in pediatric patients with narcolepsy was evaluated with the change in the Epworth Sleepiness Scale (Child and Adolescent) score. The Epworth Sleepiness Scale (Child and Adolescent) is a modified version of the Epworth Sleepiness Scale used in the adult clinical trial with immediate-release sodium oxybate. The Epworth Sleepiness Scale is intended to evaluate the extent of sleepiness in everyday situations by asking the patient a series of questions. In these questions, patients were asked to rate their chances of dozing during each of 8 activities on a scale from 0-3 (0=never; 1=slight; 2=moderate; 3=high). Higher total scores indicate a greater tendency to sleepiness. The overall change in narcolepsy condition was assessed by the Clinical Global Impression of Change for narcolepsy overall. Efficacy was assessed during or at the end of the 2-week double-blind treatment period, relative to the last 2 weeks or end of the stable-dose period (see Tables 6 and 7).

Pediatric patients taking stable dosages of immediate-release sodium oxybate who were withdrawn from immediate-release sodium oxybate treatment and were randomized to placebo during the double-blind treatment period experienced a statistically significant increase in weekly cataplexy attacks compared with patients who were randomized to continue treatment with immediate-release sodium oxybate. Patients randomized to receive placebo during the double-blind treatment period experienced a statistically significant worsening of EDS compared with patients randomized to continue receiving immediate-release sodium oxybate (see Table 6).

Patients randomized to receive placebo during the double-blind treatment period experienced a statistically significant worsening of cataplexy severity and narcolepsy overall according to the clinician’s assessment compared with patients randomized to continue receiving immediate-release sodium oxybate (see Table 7).