Findings indicated that the robust wake-promoting efficacy of solriamfetol demonstrated in clinical trials resulted in improved real-world functional performance in participants with narcolepsy.
Recently published data from a randomized, placebo-controlled, crossover study (NCT02806908) showed that treatment with solriamfetol (Sunosi; Jazz Pharmaceuticals) at 150 mg/day for 3 days followed by 300 mg/day for 4 days significantly improved driving performance in patients with narcolepsy.
Participants, aged 21 to 75 years old with a diagnosis of narcolepsy, completed a standardized on-road driving test conducted at 2 hours and 6 hours after administration of solriamfetol or placebo. After 2 hours post-dose, the median standard deviation of lateral position (SDLP), or primary end point, was significantly lower (improved) with solriamfetol relative to placebo (19.08 vs 20.46 cm; P = .002).
Senior investigator Annemiek Vermeeren, MD, assistant professor, Faculty of Psychology and Neuroscience, Maastricht UMC, and colleagues randomly assigned patients 1:1 to either solriamfetol followed by placebo or placebo followed by solriamfetol. Treatment periods consisted of 7 days, with no washout between the 2 periods. Of note, the study was initiated before the regulatory approval of solriamfetol or dosing recommendations were finalized; therefore, the 300-mg dose was based on prior phase 2 studies and was consistent with the maximum dose used in phase 3 trials, although it exceeds the currently approved maximum dose.
On day 7 and 14, visits were conducted to evaluate driving performance. A safety follow-up visit was conducted approximately 1 week after completion of period 2. On non-test days, patients took a single capsule orally once daily, within 1 hour of waking in the morning, on an empty stomach, and then were asked to wait at least 30 minutes before having breakfast. Caffeine users were instructed not to increase their use during the study, and nicotine users were instructed to maintain a consistent level of use.
After screening 29 participants, 22 made up the intention-to-treat population, all of whom completed the study. At 2 hours post-dose, the median between-group difference in SDLP, a measure of “weaving” or road-tracking control, was –1.1 cm (range, –12.1 to 6.0; P = .125). There were 12 participants who had at least 1 incomplete driving test, which was more common in the placebo group compared with solriamfetol at both 2 hour post-dose and 6 hours post-dose. For both arms, at 2 hours post-dose, more tests were stopped by the instructor than the participants, whereas more tests were stopped by the participant at 6 hours post-dose.
READ MORE: Polysomnography More Commonly Used in Narcolepsy Detection Prior to Multiple Sleep Latency Test
At 2 and 6 hours post-dose, standard deviation of speed and number of drifts, secondary end points, did not differ between solriamfetol and placebo. Despite this, investigators observed higher Toronto Hospital Alertness Test (THAT) scores, a measurement of perceived alertness over the preceding week, in the solriamfetol group than placebo. The least square mean THAT score with placebo was 26.8 (standard error [SE], 1.4) vs mean scores of 34.0 (SE, 1.4) in those on solriamfetol.
The improvement in THAT scores was consistent with the established wake-promoting effects of solriamfetol on other measures, such as the Epworth Sleepiness Scale and MWT. In the phase 3 trial of solriamfetol in patients with narcolepsy, there were differences from placebo of –2.2 to –4.7 points and 2.6-10.1 min, respectively, on these outcomes, after 12 weeks of treatment. These wake-promoting effects have also been shown to be maintained for up to 12 months in an open-label extension study.2,3
In terms of safety, Vinckenbosch et al identified treatment-emergent adverse events (TEAEs) in 83% of the cohort, with higher rates observed while on solriamfetol (n = 17; 74%) than placebo (n = 6; 26%). There were no serious or fatal TEAEs, and 1 participant in the placebo group discontinued because of nausea and vomiting. Changes from baseline in systolic and diastolic blood pressure and pulse rate were generally small, and their occurrence was proportionately similar between the 2 treatment groups and across treatment periods/visits.