S1 Biopharma, a developer of first-in-class drugs for sexual dysfunction in women and men, has announced enrollment and dosing of premenopausal women with hypoactive sexual desire disorder (HSDD) in the phase IIa clinical trial of its leading drug candidate Lorexys (S1P-104).

"The initiation of this study marks a milestone for S1 Biopharma as we advance Lorexys' clinical development," said Nicolas G. Sitchon, chief executive officer of S1 Biopharma. "Despite significant effort over many years, there are no FDA-approved treatments for women with HSDD. We believe Lorexys may provide the first safe and effective treatment option for those whose lives and the lives of their partners are affected by the disorder. By restoring the balance of the key neurotransmitters that regulate sexual desire in the brain, we expect Lorexys will help women with sexual desire and arousal disorders regain a healthy sexual life."

The scientific model of the regulation of sexual desire in the brain is the Kinsey dual control model. It explains that sexual inhibition and sexual excitation are kept in balance by activating and inhibiting neurotransmitters including serotonin, norepinephrine and dopamine.

"Lorexys, which is a first-in-class drug for HSDD, was formulated by identifying the two psychiatric medications, bupropion and trazodone, that, when combined in a precise, proprietary ratio, would modulate the activity of these neurotransmitters, neutralize the monoamine modulators' side effects and maximize beneficial effects on sexual function," said Robert E. Pyke, M.D., Ph.D., chief medical officer of S1 Biopharma. "Pilot data supported positive effects, unlike other serotonergic agents or combinations studied in our early drug development. S1P-205, our candidate for the treatment of HSDD in men, is based on the same active components as Lorexys but has been formulated specifically for efficacy in men."

The phase IIa study's primary objective is to evaluate Lorexys' safety, tolerability and pro-sexual efficacy as compared to bupropion, one of its constituent drugs; other objectives include exploration of the onset and extent of action of Lorexys, as well as the optimal dose.

Pyke said, "This phase IIa trial has been designed specifically to capture clinical data on efficacy and safety in a way that will allow us to move Lorexys carefully yet efficiently into late-stage clinical development."

The clinical trial has an adaptive, three-way crossover, open-label design. It is enrolling 30 subjects meeting the DSM-IV-TR criteria for HSDD, and is the first trial to also assess such patients for the newly defined DSM-5 Sexual Interest and Arousal Disorder. Each subject will receive a daily dose of bupropion as an active control for four weeks followed by a week-long washout period, then a daily administration of a low dose of Lorexys for four weeks followed by the washout and finally a moderate dose of Lorexys followed by another washout. Patients will self-evaluate weekly with questionnaires and be examined at eight clinic visits. Outcome measures for efficacy include validated self-rated scales of Sexual Function and Sexual Distress and global change. Outcome measures for safety include comprehensive evaluations of symptoms and vital signs, plus standard laboratory studies and electrocardiograms.

The study will be conducted in up to three clinical sites in the U.S. Data are expected in the first quarter of 2014.