To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women.
Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive.
The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index–desire domain score and Female Sexual Distress Scale–Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and −1.4 to −1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70–0.77 and −0.9, respectively, for patients who received placebo during the core phase.
During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms.
ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).
Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.
George Washington University and IntimMedicine Specialists, Washington, DC; University Hospitals Cleveland Medical Center, Cleveland, and Sermonix Pharmaceuticals, Columbus, Ohio; AMAG Pharmaceuticals, Inc., Waltham, Massachusetts; Palatin Technologies, Inc., Cranbury, New Jersey; and the University of Virginia, Charlottesville, Virginia.
Corresponding author: James A. Simon, MD, George Washington University and IntimMedicine Specialists, Washington, DC; email: jsimon@IntimMedicine.com.
The RECONNECT studies were sponsored and funded by Palatin Technologies, Inc., the innovator of bremelanotide. Editorial support in the preparation of this manuscript was provided by Phase Five Communications, supported by AMAG Pharmaceuticals, Inc., the licensee of bremelanotide.
Financial Disclosure Dr. Simon has served on advisory boards or has been a consultant for AbbVie, Allergan, AMAG Pharmaceuticals, Inc., Amgen, Ascend Therapeutics, Azure Biotech, Bayer HealthCare Pharmaceuticals, Inc., CEEK Enterprises, Covance Inc., Daré Bioscience, Duchesnay, Hologic Inc., KaNDy/NeRRe Therapeutics Ltd., Millendo, Mitsubishi Tanabe Pharma, ObsEva, Radius Health, Sanofi, Sebela, Sermonix, Shionogi, Symbiotec Pharmalab, TherapeuticsMD, and Valeant. He has also served on the speaker's bureau for AbbVie, AMAG Pharmaceuticals, Inc., Duchesnay, Novo Nordisk, Shionogi, and Valeant. He has received grants/research funding from AbbVie, Allergan, Agile Therapeutics, Bayer Healthcare LLC, Dornier MedTech, Endoceutics Inc., GTx Inc., Hologic Inc., Myovant Sciences, New England Research Institutes, ObsEva, Palatin Technologies, Inc., Symbio Research, TherapeuticsMD, Tissue Genesis, and Viveve Medical. He owns stock in Sermonix. Dr. Kingsberg has served on advisory boards or has been a consultant for AMAG Pharmaceuticals, Inc., Daré Bioscience, Duchesnay, Emotional Brain, Valeant, Endoceutics, Ivix, Palatin Technologies, Inc., Pfizer, Shionogi, Materna, Nuelle, Mitsubishi Tanaka North America, TherapeuticsMD, SST, and Lupin/Symbiomix. She has stock options in Viveve Medical. Dr. Portman has served on advisory boards or has been a consultant to AMAG Pharmaceuticals, Inc., Palatin Technologies, Inc., Endoceutics, Valeant Pharmaceuticals and Sprout, and is on the speaker's bureau for AMAG Pharmaceuticals, Inc. He is an employee and stockholder of Sermonix Pharmaceuticals. Dr. Williams and Dr. Krop are employees and stockholders of AMAG Pharmaceuticals, Inc. (the licensee of bremelanotide). Mr. Jordan is Vice President, Clinical Operations and Project Management, and a stockholder of Palatin Technologies, Inc. (the sponsor of the trial). He has a BS in Biology and has worked in clinical development for over 20 years. He led the Palatin team in the development of bremelanotide (clinical, regulatory, etc.) since 2007, including having a very significant role in designing the phase 3 studies, conduct of the studies, and analysis of the data. Dr. Lucas was an employee of Palatin Technologies, Inc. at the time of the study. She has no remaining financial interests in Palatin Technologies. She was the medical lead for the entire trial. She was the physician who ran the trial and provided safety evaluation and analysis for all adverse events as they occurred during the trial. She was also responsible for aggregate assessment of the adverse event database. She was the physician who provided medical information to the DSMB during the trial. Dr. Clayton has served on advisory boards or has been a consultant for Acadia, Alkermes, Allergan, AMAG Pharmaceuticals, Inc., Fabre Kramer, Ivix, Lundbeck, Palatin Technologies, Inc., S1 Biopharma, Sage Therapeutics, Sprout Pharmaceuticals, and Takeda. She has received grants from Endoceutics, Inc., Janssen, Sage Therapeutics, and Takeda. In addition, she has received royalties and/or owns copyright to works published by Ballantine Books/Random House and Guilford Publications, and the Changes in Sexual Functioning Questionnaire. She has shares or restricted stock units in Euthymics and S1 Biopharma.
Presented at the Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists, April 27–29, 2018, Austin, Texas.
The authors thank all participants in these studies, their families, and personnel at all study sites.
Each author has confirmed compliance with the journal's requirements for authorship.
Peer reviews are available at http://links.lww.com/AOG/B588.
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