David J Portman1, Louise Brown2, James Yuan2, Robert Kissling2, Sheryl A Kingsberg3. 1. Columbus Center for Women's Health Research, Columbus, OH, USA. Electronic address: davidportman@earthlink.net. 2. Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, USA. 3. Case Western Reserve University, Cleveland, OH, USA.
Abstract
BACKGROUND:Hypoactive sexual desire disorder (HSDD) is a common sexual disorder in younger and older women. Flibanserin is approved for the treatment of acquired generalized HSDD in premenopausal women only. The efficacy of flibanserin for postmenopausal women with HSDD was demonstrated in the first of two North American randomized, double-blinded, placebo-controlled trials (SNOWDROP). AIM: To evaluate the safety and efficacy of flibanserin in postmenopausal women with HSDD in a second randomized, double-blinded, placebo-controlled trial (PLUMERIA). METHODS:Naturally postmenopausal women were randomly assigned to receive flibanserin (100 mg/d) or placebo. Efficacy outcomes were assessed using the last-observation-carried-forward imputation method. OUTCOMES: Safety assessment included incidence of adverse events. Primary efficacy outcomes were the number of satisfying sexual events and the Female Sexual Function Index desire domain (FSFI-d) score. RESULTS:The study population (flibanserin, n = 376; placebo, n = 369) included primarily white women (84.7%), with a mean age of 56.1 years and a mean HSDD duration of 5.0 years. When the study was discontinued early by the sponsor, 45.3% of randomly assigned patients had completed week 16 (which served as the primary analysis time point). The most common adverse events in flibanserin-treated patients were insomnia (7.7%), somnolence (6.9%), and dizziness (6.4%). Improvement from baseline to week 16 (last-observation-carried-forward) in FSFI-d score was significantly greater for flibanserin compared with placebo (P = .011); however, the between-group comparison for satisfying sexual events did not reach statistical significance. CLINICAL IMPLICATIONS: Considered with the findings of the previous randomized controlled trial (SNOWDROP), the results of this study support the safety and efficacy of flibanserin in postmenopausal women. STRENGTHS AND LIMITATIONS: This was a well-designed randomized, placebo-controlled trial. A key limitation was early discontinuation by the study sponsor, which decreased the sample size. In addition, the validity of satisfying sexual events as a primary outcome measurement in HSDD studies has been called into question (but was required by the US Food and Drug Administration as a primary end point in studies of female sexual dysfunction at the time this study was conducted). CONCLUSION:Flibanserin was generally well tolerated in this population of naturally postmenopausal women. Despite the greatly decreased power to detect improvement compared with placebo on the efficacy measurements used, results suggest that flibanserin could be efficacious in postmenopausal women with HSDD. Portman DJ, Brown L, Yuan J, et al. Flibanserin in Postmenopausal Women With Hypoactive Sexual Desire Disorder: Results of the PLUMERIA Study. J Sex Med 2017;14:834-842.
RCT Entities:
BACKGROUND:Hypoactive sexual desire disorder (HSDD) is a common sexual disorder in younger and older women. Flibanserin is approved for the treatment of acquired generalized HSDD in premenopausal women only. The efficacy of flibanserin for postmenopausal women with HSDD was demonstrated in the first of two North American randomized, double-blinded, placebo-controlled trials (SNOWDROP). AIM: To evaluate the safety and efficacy of flibanserin in postmenopausal women with HSDD in a second randomized, double-blinded, placebo-controlled trial (PLUMERIA). METHODS: Naturally postmenopausal women were randomly assigned to receive flibanserin (100 mg/d) or placebo. Efficacy outcomes were assessed using the last-observation-carried-forward imputation method. OUTCOMES: Safety assessment included incidence of adverse events. Primary efficacy outcomes were the number of satisfying sexual events and the Female Sexual Function Index desire domain (FSFI-d) score. RESULTS: The study population (flibanserin, n = 376; placebo, n = 369) included primarily white women (84.7%), with a mean age of 56.1 years and a mean HSDD duration of 5.0 years. When the study was discontinued early by the sponsor, 45.3% of randomly assigned patients had completed week 16 (which served as the primary analysis time point). The most common adverse events in flibanserin-treated patients were insomnia (7.7%), somnolence (6.9%), and dizziness (6.4%). Improvement from baseline to week 16 (last-observation-carried-forward) in FSFI-d score was significantly greater for flibanserin compared with placebo (P = .011); however, the between-group comparison for satisfying sexual events did not reach statistical significance. CLINICAL IMPLICATIONS: Considered with the findings of the previous randomized controlled trial (SNOWDROP), the results of this study support the safety and efficacy of flibanserin in postmenopausal women. STRENGTHS AND LIMITATIONS: This was a well-designed randomized, placebo-controlled trial. A key limitation was early discontinuation by the study sponsor, which decreased the sample size. In addition, the validity of satisfying sexual events as a primary outcome measurement in HSDD studies has been called into question (but was required by the US Food and Drug Administration as a primary end point in studies of female sexual dysfunction at the time this study was conducted). CONCLUSION:Flibanserin was generally well tolerated in this population of naturally postmenopausal women. Despite the greatly decreased power to detect improvement compared with placebo on the efficacy measurements used, results suggest that flibanserin could be efficacious in postmenopausal women with HSDD. Portman DJ, Brown L, Yuan J, et al. Flibanserin in Postmenopausal Women With Hypoactive Sexual Desire Disorder: Results of the PLUMERIA Study. J Sex Med 2017;14:834-842.
Authors: Debra L Barton; Stephanie L Pugh; Patricia A Ganz; Steven C Plaxe; Bridget F Koontz; Jeanne Carter; Natalya Greyz-Yusupov; Seth J Page; Kendrith M Rowland; Ernie P Balcueva; Sobia Nabeel; Jack B Basil; Matthew L Hill; Carolyn Y Muller; Maria C Bell; Snehal Deshmukh; Lisa A Kachnic Journal: J Clin Oncol Date: 2021-12-09 Impact factor: 44.544
Authors: Sheryl A Kingsberg; Jonathan Schaffir; Brooke M Faught; JoAnn V Pinkerton; Sharon J Parish; Cheryl B Iglesia; Jennifer Gudeman; Julie Krop; James A Simon Journal: J Womens Health (Larchmt) Date: 2019-02-04 Impact factor: 2.681
Authors: Amber N Edinoff; Nicole M Sanders; Kyle B Lewis; Tucker L Apgar; Elyse M Cornett; Adam M Kaye; Alan D Kaye Journal: Neurol Int Date: 2022-01-04
Authors: Lauren L Zimmerman; Priyanka Gupta; Florence O'Gara; Nicholas B Langhals; Mitchell B Berger; Tim M Bruns Journal: Neuromodulation Date: 2018-09-03