PT-141

Authors:

Adam M Kaye, Alan D Kaye, Amber N Edinoff, Elyse M Cornett, Kyle B Lewis, Nicole M Sanders, Tucker L Apgar

Findings:

In two phase 3 trials, bremelanotide significantly improved sexual desire and reduced related distress in premenopausal women with hypoactive sexual desire disorder compared to placebo. The safety profile was favorable, with most treatment-emergent adverse events (nausea, flushing, headache occurring in 10% or more) being mild or moderate in intensity.

Participants:

Premenopausal women with hypoactive sexual desire disorder. 1,267 women were randomized; 1,247 were in the safety population and 1,202 in the efficacy (modified intent-to-treat) population. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years.

Dosage:

Bremelanotide 1.75 mg administered subcutaneously as needed. Treatment duration was 24 weeks.

Study Quality Assessment:

Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT). Sample size: 1,267 women randomized; 1,247 in safety population, 1,202 in efficacy (modified intent-to-treat) population. Sample size estimation method based on prior trial data mentioned. Clinical trial registration: ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). Funding source disclosed: Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc. Adverse events (nausea, flushing, headache) reported as more common with bremelanotide but mostly mild or moderate.

All Effects:

Authors:

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

Participants:

Individuals with hypoactive sexual desire disorder

Study Quality Assessment:

two randomized phase 3 trials

Findings:

The most common adverse events (AEs) with bremelanotide versus placebo in phase 3 studies were nausea (40.0% vs. 1.3%), flushing (20.3% vs. 1.3%), headache (11.3% vs. 1.9%), and injection site reactions (5.4% vs. 0.5%). Nausea was the most common reason for bremelanotide discontinuation. Focal hyperpigmentation was rare with recommended dosing but occurred in over one-third of subjects with up to 16 consecutive daily dosings. Small, transient, statistically significant blood pressure increases and some drug-drug interactions (lowered plasma concentrations of indomethacin and naltrexone) were observed. AEs were mostly mild to moderate, but bremelanotide should be used with caution in patients at risk of cardiovascular disease.

Participants:

The clinical development program comprised 3500 subjects. The FDA-approved indication is for premenopausal women with acquired, generalized hypoactive sexual desire disorder. The integrated double-blind portion of the phase 3 studies included N = 1247 subjects.

Dosage:

In the phase 3 studies, subjects took bremelanotide for up to 18 months. Focal hyperpigmentation occurred in more than one-third of subjects following up to 16 consecutive daily dosings. Bremelanotide was dosed in accordance with label recommendations (specifics not detailed in abstract).

Study Quality Assessment:

Review of bremelanotide's safety profile from the clinical development program (phases 1 through 3), comprising 43 completed studies. The phase 3 studies included an integrated double-blind portion (N = 1247) with placebo groups. Ambulatory blood pressure monitoring was used. Clinical Trial Registration numbers: NCT02333071 [Study 301] and NCT02338960 [Study 302].

All Effects: