The efficacy of SUNOSI in improving wakefulness and reducing excessive daytime sleepiness was demonstrated in a 12-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study (Study 1; NCT02348593) in adult patients with a diagnosis of narcolepsy according to the ICSD-3 or DSM-5 criteria.

Wakefulness and sleepiness were assessed using the Maintenance of Wakefulness Test (MWT) and the Epworth Sleepiness Scale (ESS). The MWT measures an individual’s ability to remain awake during the daytime in a darkened, quiet environment. Patients were instructed to remain awake for as long as possible during 40-minute test sessions, and sleep latency was determined as the mean number of minutes patients could remain awake in the first four test sessions. The ESS is an 8-item questionnaire by which patients rate their perceived likelihood of falling asleep during usual daily life activities. Change in overall symptom severity was assessed using the Patient Global Impression of Change (PGIc) scale. The PGIc is a 7-point patient-reported scale by which patients rate their symptom change since the beginning of the study. Responses range from “very much improved” to “very much worse.” The co-primary efficacy endpoints were change from baseline in MWT and ESS at Week 12. A pre-specified secondary endpoint was percentage of subjects reported as improved (minimally, much, or very much) at Week 12 by PGIc.

A total of 239 patients with narcolepsy were randomized to receive SUNOSI 75 mg, 150 mg, or 300 mg (two times the maximum recommended daily dose), or placebo once daily. Patients randomized to the 150-mg dose received 75 mg for the first 3 days before increasing to 150 mg.

Demographic and baseline disease characteristics were similar for the SUNOSI and placebo groups. Median age was 34 years (range 18 to 70 years), 65% were female, 80% were Caucasian, 14% were African American, and 3% were Asian. Approximately 51% of patients had cataplexy.

Compared to the placebo group, patients randomized to 150 mg SUNOSI showed statistically significant improvements on the MWT (treatment effect difference: 7.7 minutes, Table 6) and on the ESS (treatment effect difference: 3.8 points, Table 7) at Week 12. These effects were apparent at Week 1 and consistent with the results at Week 12. The change on percentage of subjects reported as improved by PGIc was also statistically significant compared with placebo. There were trends toward improvement in the SUNOSI 75-mg treatment group (Tables 6 and 7); however, these changes were not statistically significant. There was no evidence of differential efficacy in patients with cataplexy and patients without cataplexy. Examination of subgroups by age, race, and sex did not suggest differences in response.

At Week 12, 150 mg of SUNOSI demonstrated improvements in wakefulness compared to placebo as assessed in test sessions 1 (approximately 1 hour post-dose) through 5 (approximately 9 hours post-dose) of the MWT (Figure 2). Nighttime sleep as measured with polysomnography was not affected by the use of SUNOSI in Study 1.

Figure 2: Maintenance of Wakefulness Test Improvements in Test Sessions 1 through 5 in Patients with Narcolepsy in Study 1 at Week 12