OSA-Related Sleepiness Reduced with Experimental Therapy

The selective dopamine norepinephrine reuptake inhibitor JZP-110, which has wake-promoting effects, effectively decreased excessive sleepiness among patients with obstructive sleep apnea (OSA), according to a recent trial.

The phase 3 pivotal trial included 474 patients who were receiving current treatment or had received treatment for OSA (mean age 53.9 years, 63% men). Patients were randomly assigned to receive once-daily JZP-110 at 37.5 mg, 75 mg, 150 mg, or 300 mg or placebo for 12 weeks.

RELATED CONTENT
Could CPAP Improve Risk of CVD Events in Sleep Apnea Patients?
Sleep Better, Think Better: Insomnia May Be Linked to Mental Health
Sleep-Disordered Breathing Could Raise Risk of Cognitive Impairment

In their analysis, the researchers stratified patients by adherence or nonadherence to primary OSA therapy. They assessed changes in sleep latency using the 40-minute Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) scores from baseline to 12 weeks as the primary endpoints. Additionally, the percentage of patients who reported any improvements on the Patient Global Impression of Change scale (PGI-C), as well as the safety and tolerability of the drug, was assessed as the secondary endpoint.

Overall, 404 (85.2%) patients completed the study and 459 were evaluated for efficacy in a pre-specified, modified intent-to-treat population. The mean baseline MWT sleep latency was 12.6 minutes and the mean baseline ESS score was 15.2.

After 12 weeks of treatment, the least square (LS) mean (SE) change from baseline in MWT was significantly higher among patients who received JZP-110 compared with placebo: 4.7 (1.4) min, 9.1 (1.4) min, 11.0 (1.0) min, and 13.0 (1.0) min for 37.5mg, 75mg, 150mg, and 300mg, respectively.

Likewise, the LS mean (SE) changes in ESS scores were -5.1 for 37.5 mg, -5.0 for 75 mg, -7.7 for 150 mg, and -7.9 for 300 mg compared with -3.3 for placebo. 

In addition, a significantly higher percentage of patients who received 75 mg, 150 mg, and 300 mg doses of JZP-110 reported PGI-C improvement at 12 weeks compared with placebo (72.4%, 89.7%, and 88.7% vs 49.1%, respectively). However, patients receiving 37.5 mg of JZP-110 did not experience any significant changes at 12 weeks (55.4%). 

Adverse events were reported by 47.9% of patients in the placebo group and 67.9% of patients in the JZP-110 groups. Among those who received JZP-110, the most common adverse event was headache (10.1%), followed by nausea (7.9%), decreased appetite (7.6%), and anxiety (7%). Six patients reported serious adverse events but none were deemed related or suspected to be related to the study drug.

“In this population, JZP-110 resulted in significant and dose-dependent increases in wakefulness on the MWT, decreases in patient-reported sleepiness on the ESS, and improvement on the PGI-C,” the researchers concluded. “The [adverse events] appeared to be dose dependent.”

—Melissa Weiss

Reference:

Strohl K, Zammit G, Gotfried M, et al. Results of a randomized, placebo-controlled, double-blind, 12-week, multicenter study of Jzp-110 for the treatment of excessive sleepiness in patients with OSA. Presented at: CHEST Annual Meeting 2017; Toronto, CA; Oct 28-Nov 1, 2017. http://dx.doi.org/10.1016/j.chest.2017.08.1097.