PMID-31599840 – RECONNECT Pivotal Trials Bremelanotide for HSDD
Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. "Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials," Obstet Gynecol, 2019;134(5):899-908.
Quick Reference
| Property | Value |
|---|---|
| PMID | 31599840 |
| DOI | 10.1097/AOG.0000000000003500 |
| Year | 2019 |
| Journal | Obstetrics & Gynecology |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=1,267 premenopausal women with HSDD |
| Peptide(s) Studied | PT-141 |
Key Findings
- Two replicate Phase 3, randomized, double-blind, placebo-controlled trials (RECONNECT)
- 1,267 premenopausal women with generalized acquired HSDD randomized to bremelanotide 1.75 mg SC or placebo
- Self-administered subcutaneously as needed, at least 45 minutes before anticipated sexual activity
- Statistically significant improvement in Female Sexual Function Index (FSFI) desire domain score vs placebo in both trials
- Significant reduction in distress as measured by the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) Item 13
- Most common adverse event was nausea (~40% vs ~1% placebo), generally mild and decreasing over time
- Transient increases in blood pressure were observed but not clinically significant
- These pivotal trials directly supported the FDA approval of bremelanotide (Vyleesi) in June 2019
Study Design
Two replicate randomized, double-blind, placebo-controlled Phase 3 trials. Premenopausal women with generalized acquired HSDD self-administered bremelanotide 1.75 mg SC or placebo as needed over 24 weeks, with a maximum of one dose per 24-hour period and no more than 8 doses per month. Co-primary endpoints were change from baseline in FSFI desire domain score and FSDS-DAO Item 13 score.
Limitations
- High nausea rate (~40%) may limit real-world adherence
- Subcutaneous injection route less convenient than oral alternatives
- 24-week duration; long-term efficacy and safety data from open-label extension needed
- Excluded postmenopausal women, limiting generalizability
- Moderate effect sizes — clinical significance debated by some reviewers
Clinical Relevance
The RECONNECT trials are the registration-enabling studies for bremelanotide (Vyleesi), the first and only FDA-approved on-demand treatment for HSDD in premenopausal women. They establish that central melanocortin receptor activation can meaningfully improve sexual desire and reduce associated distress. The as-needed SC dosing model is unique among HSDD treatments (flibanserin requires daily oral dosing). These data are foundational for understanding PT-141's clinical utility in sexual health protocols.
Related
#research #RCT #evidence-level-I