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J Sex Med. 2019 Aug;16(8):1226-1235. doi: 10.1016/j.jsxm.2019.05.012. Epub 2019 Jul 2.

Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide.

Author information

1
Case Western Reserve University School of Medicine, Department of Psychiatry, Cleveland, OH, USA. Electronic address: Stanley.Althof@case.edu.
2
Maryland Center for Sexual Health, Lutherville, MD, USA.
3
S. Greenberg Statistical Consulting Inc, Berkeley, CA, USA.
4
University of Virginia, Department of Psychiatry, Charlottesville, VA, USA.
5
Palatin Technologies, Inc, Cranbury, NJ, USA.

Abstract

BACKGROUND:

Responder analyses are used to determine whether changes that occur during a clinical trial are clinically meaningful; for subjective endpoints such as those based on patient-reported outcomes (PROs), responder analyses are particularly useful.

AIM:

To identify the minimal clinically important difference (MCID) for selected scores on questionnaires assessing female sexual functioning and to use these differences to analyze the response in a large, controlled, phase 2b, dose-finding study of bremelanotide in premenopausal women with hypoactive sexual desire disorder (HSDD) and mixed HSDD/female sexual arousal disorder (FSAD).

METHODS:

The responder analyses were performed for the change from baseline to end of study for a total of 7 endpoints. Each PRO endpoint was assessed using at least 1 of 4 types of responder analyses: a planned analysis anchored to MCIDs based on expert estimates (historical anchors); post hoc analyses based on self-reported global benefit; receiver operating characteristic (ROC) curves; and cumulative distribution function. The prespecified analysis groups were all female sexual dysfunction (FSD)-based diagnoses (all study participants), those with HSDD alone, and a combined group of those with FSAD alone plus those with mixed HSDD/FSAD. Post hoc analyses were also performed for subjects with mixed HSDD/FSAD with a primary diagnosis of HSDD.

OUTCOMES:

MCIDs based on the ROC curves for changes in Female Sexual Function Index-desire domain, Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) total score, FSDS-DAO item 13 and 14 scores, and number of satisfying sexual events.

RESULTS:

Outcomes matched those based on input from clinical experts. For all 7 endpoints, responder rates at the 1.75 mg dose in the overall modified intention-to-treat population achieved statistical significance compared with placebo (P ≤ .03).

CLINICAL IMPLICATIONS:

These responder definitions were subsequently used in the bremelanotide phase 3 registration studies (RECONNECT) that evaluated the safety and efficacy of the bremelanotide 1.75 mg subcutaneous dose in premenopausal women with HSDD.

STRENGTHS & LIMITATIONS:

MCIDs for this study were based on changes from a single-blind phase to account for changes due to the placebo effect. These analyses were restricted to a study population composed only of premenopausal women with a clinical diagnosis of HSDD and/or FSAD and were based on data from the same clinical trial.

CONCLUSION:

Bremelanotide was safe and well tolerated and demonstrated significant improvement in efficacy vs placebo in the phase 2b trial. The multiple responder analyses offer a valuable approach for determining clinically important effects of bremelanotide for HSDD and FSAD. Althof S, Derogatis LR, Greenberg S, et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med 2019;16:1226-1235.

KEYWORDS:

Bremelanotide; Female Sexual Dysfunction; Hypoactive Sexual Desire Disorder; Minimal Clinically Important Difference; Responder Analyses

PMID:
31277966
DOI:
10.1016/j.jsxm.2019.05.012

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