Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials

Sheryl A Kingsberg, Anita H Clayton, David Portman, Laura A Williams, Julie Krop, Robert Jordan, Johna Lucas, James A Simon, Sheryl A Kingsberg, Anita H Clayton, David Portman, Laura A Williams, Julie Krop, Robert Jordan, Johna Lucas, James A Simon

Abstract

Objective: To evaluate the safety and efficacy of bremelanotide for the treatment of premenopausal women with hypoactive sexual desire disorder.

Methods: Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT) evaluated the safety and efficacy of bremelanotide 1.75 mg administered subcutaneously as needed in premenopausal women with hypoactive sexual desire disorder. Patients were randomized 1:1 to 24 weeks of treatment with bremelanotide or placebo. Sample size was estimated based on simulations from key endpoints in patients with hypoactive sexual desire disorder from a prior trial. Coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13.

Results: Study 301 began on January 7, 2015, and concluded on July 26, 2016. Study 302 began on January 28, 2015, and concluded on August 4, 2016. Of the 1,267 women randomized, 1,247 and 1,202 were in the safety and efficacy (modified intent-to-treat) populations, respectively. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years. From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: -0.37, P<.001; study 302: -0.29, P=.005; integrated studies -0.33, P<.001) compared with placebo. Patients taking bremelanotide experienced more nausea, flushing, and headache (10% or more in both studies) compared with placebo.

Conclusions: Both studies demonstrated that bremelanotide significantly improved sexual desire and related distress in premenopausal women with hypoactive sexual desire disorder. The safety profile was favorable. Most treatment-emergent adverse events were related to tolerability and the majority were mild or moderate in intensity.

Clinical trial registration: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).

Funding source: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

Figures

Fig. 1.. Co-primary endpoints and key dynamic…
Fig. 1.. Co-primary endpoints and key dynamic anchor over the course of the core phase of the phase 3 studies (modified intent-to-treat population). A. Female Sexual Function Index–desire domain (FSFI-D). B. Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO). C. General Assessment Questionnaire (GAQ) question 3 responders (≥5, dynamic anchor). A and B. Estimated treatment difference and P value from mixed-model repeated measures using change from baseline of all double-blind period data (baseline through core week 24), with uncorrelated covariance structure. C. P value from unadjusted Wilcoxon rank-sum test. Scores range from 1 (very much worse) to 7 (very much better). Summary statistics are based on the number of nonmissing values. Error bars for integrated populations represent 95% CIs. BMT, bremelanotide.
Kingsberg. Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol 2019.
Fig. 2.. Percentage of sexual encounters that…
Fig. 2.. Percentage of sexual encounters that were satisfying sexual events (modified intent-to-treat populations, post hoc analysis). No significant difference between treatment groups was observed for satisfying sexual events associated with study drug and reported within 72 hours.
Kingsberg. Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol 2019.
Fig. 3.. Forest plot of supportive secondary…
Fig. 3.. Forest plot of supportive secondary efficacy endpoints in the phase 3 studies (modified intent-to-treat population). Q, question; FSEP-R, Female Sexual Encounter Profile–Revised; BMT, bremelanotide; FSDS-DAO, Female Sexual Distress Scale–Desire/Arousal/Orgasm; FSFI, Female Sexual Function Index; PBO, placebo.
Kingsberg. Bremelanotide for Hypoactive Sexual Desire Disorder. Obstet Gynecol 2019.
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