Minerva Neurosciences Inc’s preliminary results from a Phase 1 clinical study showed that treatment with MIN-202, a selective orexin-2 antagonist, resulted in significant improvements in sleep onset and sleep duration in patients with comorbid insomnia related to major depressive disorder (MDD). Preliminary results from two additional Phase 1 studies also suggest that MIN-202 is well tolerated and possesses advantageous pharmacokinetic and pharmacodynamic features. The three Phase 1 studies were conducted by Janssen Research & Development, LLC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, as part of a collaboration to develop MIN-202 with Minerva that was facilitated by Johnson & Johnson Innovation Ltd in London.

“Treatment of sleep disorders remains a significant challenge in patients with both primary insomnia and many CNS diseases. These positive data indicate that MIN-202 could be an effective treatment able to both induce and maintain sleep,” says Remy Luthringer, PhD, president and CEO of Minerva, adding “with these findings we have identified a dose range to advance this compound.”

In patients with mood disorders, sleep disturbances (both insomnia and hypersomnia) have been associated with a suboptimal response to antidepressant drug (AD) therapy, an increased risk for relapse (in AD-responsive patients), and prodromal depression. Recent studies have shown that orexin-2 receptor antagonism might have a beneficial effect on overall arousal and stress level.

“We are especially encouraged by findings that support the use of MIN-202 in the treatment of both primary insomnia as well as sleep disorders associated with MDD,” Luthringer says.

MIN-202 Phase 1b Study in MDD Patients

This was a double-blind, placebo-controlled, randomized, four-way crossover, single dose study in 20 male and female patients with MDD and insomnia. The primary endpoint was the effect of MIN-202 (dosed PM) on latency to persistent sleep (LPS). Some additional endpoints were evaluated by polysomnography. Preliminary results demonstrated a statistically significant effect on LPS in all three doses tested (10, 20, and 40 mg). Treatment with MIN-202 also resulted in prolonged total sleep duration by approximately 45 minutes.

MIN-202 Phase 1 Multiple Ascending Dose (MAD) Study in Healthy Volunteers

This was a double-blind, placebo-controlled, randomized MAD study in sequential cohorts of healthy males and females. MIN-202 was administered in the morning at dose levels ranging from 5 mg to 60 mg for 10 days. A dose level as low as 5 mg was shown to elicit sedation while dose levels ?20 mg induced (daytime) somnolence. MIN-202 plasma exposure was dose proportional from 5 mg to 20 mg. At higher doses, the exposure was less than dose proportional.

MIN-202 Phase 1 Bio-Availability (BA) Study

The two studies described above were carried out using a suspension formulation of MIN-202. This third study evaluated treatment with a solid dose formulation of MIN-202 to potentially support additional clinical studies. In this study, similar pharmacokinetic profiles were observed for both formulations, qualifying the solid dose to support further clinical studies.

In these Phase 1 studies, MIN-202 was found to be generally well tolerated.