Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women.

INTRODUCTION

Prior medication treatment for hypoactive sexual desire disorder (HSDD) in women has left about half the subjects without benefit. Lorexys (LOR), a proprietary combination of the stimulating/excitatory dopamine-norepinephrine reuptake inhibitor bupropion (BUP) and the sedating/inhibitory serotonergic agonist-antagonist trazodone (TRZ), was developed as a multifunctional solution for this problem.

AIM

Test efficacy, safety, and tolerability of LOR in a range of doses in a combined phase IB/IIA study in premenopausal outpatients with HSDD.

METHODS

Otherwise healthy premenopausal women from 25-50 years of age with HSDD were tested in an open-label, active-control, one-way crossover study, with three 4-week treatments of extended-release TRZ and/or sustained-release BUP. Evaluations were made before and after each treatment. A washout of at least a week followed each treatment. The order of treatments was a standard dose of BUP; a subtherapeutic dose of BUP and TRZ (LOR-low); and a threshold-therapeutic dose of BUP and TRZ (LOR-mod). A midpoint interim analysis was planned to consider adapting doses for efficacy or safety.

MAIN OUTCOME MEASURE

The primary efficacy measure was the Female Sexual Function Index, Desire domain; the main secondary efficacy measures included the Female Sexual Distress Scale-Revised 13th item, on bother about low desire, and a Patient's Global Impression of Change. The main outcome comparison was the proportions of responders. Safety measures were elicited adverse events, Epworth Sleepiness Scale, Columbia Suicide Severity Rating Scale 6-item SCREEN version, vital signs, electrocardiograms, and standard laboratory tests.

RESULTS

Interim analysis did not require altering doses. Most evaluable subjects responded to LOR-mod (at the standard thresholds for response based on minimum clinically relevant difference from baseline, 79% on Female Sexual Function Index, Desire domain, 87% on Female Sexual Distress Scale-Revised Item 13, and 79% on Patient's Global Impression of Change; each P < .05 vs BUP). As expected, close to half responded to BUP (38%, 45%, and 52%, respectively). Response to LOR-low was intermediate (not significant vs BUP). Sensitivity analyses to compensate for carryover effects supported the efficacy of LOR-mod. Elicited adverse events showed the expected profile of TRZ, but led to no sedative-type dropouts or worsening on the Epworth Sleepiness Scale.

CLINICAL IMPLICATIONS

The open-label 1-way crossover design of this phase IB/IIA study limits conclusions, but the consistency of responder analyses showing superiority of LOR-mod dose over control, and the lack of central depressant dropouts, favor further development in double-blind placebo-control trials.

STRENGTH & LIMITATIONS: Strengths include large margins of efficacy over control agent, rapid onset of action, and rigorous safety assessment. Limitations are open-label, cross-over design/lack of placebo control and 1-month duration of exposure.

CONCLUSION

Moderate-dose LOR was generally well-tolerated and was significantly more effective than BUP (active control). The results seem highly favorable compared to previously tested agents. Pyke RE, Clayton AH. Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women. J Sex Med 2019;16:1885-1894.