PMID- 31277966
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20200629
IS  - 1743-6109 (Electronic)
IS  - 1743-6095 (Linking)
VI  - 16
IP  - 8
DP  - 2019 Aug
TI  - Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide.
PG  - 1226-1235
LID - S1743-6095(19)31216-0 [pii]
LID - 10.1016/j.jsxm.2019.05.012 [doi]
AB  - 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.
CI  - Copyright (c) 2019 International Society for Sexual Medicine. Published by Elsevier 
      Inc. All rights reserved.
FAU - Althof, Stanley
AU  - Althof S
AD  - Case Western Reserve University School of Medicine, Department of Psychiatry, 
      Cleveland, OH, USA. Electronic address: Stanley.Althof@case.edu.
FAU - Derogatis, Leonard R
AU  - Derogatis LR
AD  - Maryland Center for Sexual Health, Lutherville, MD, USA.
FAU - Greenberg, Sally
AU  - Greenberg S
AD  - S. Greenberg Statistical Consulting Inc, Berkeley, CA, USA.
FAU - Clayton, Anita H
AU  - Clayton AH
AD  - University of Virginia, Department of Psychiatry, Charlottesville, VA, USA.
FAU - Jordan, Robert
AU  - Jordan R
AD  - Palatin Technologies, Inc, Cranbury, NJ, USA.
FAU - Lucas, Johna
AU  - Lucas J
AD  - Palatin Technologies, Inc, Cranbury, NJ, USA.
FAU - Spana, Carl
AU  - Spana C
AD  - Palatin Technologies, Inc, Cranbury, NJ, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190702
PL  - Netherlands
TA  - J Sex Med
JT  - The journal of sexual medicine
JID - 101230693
RN  - 0 (Peptides, Cyclic)
RN  - 581-05-5 (alpha-MSH)
RN  - 6Y24O4F92S (bremelanotide)
SB  - IM
MH  - Adult
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Libido/drug effects
MH  - Peptides, Cyclic/*administration & dosage
MH  - *Premenopause
MH  - Sexual Dysfunction, Physiological/*drug therapy
MH  - Sexual Dysfunctions, Psychological/diagnosis/*drug therapy
MH  - Single-Blind Method
MH  - Surveys and Questionnaires
MH  - alpha-MSH/*administration & dosage
OTO - NOTNLM
OT  - Bremelanotide
OT  - Female Sexual Dysfunction
OT  - Hypoactive Sexual Desire Disorder
OT  - Minimal Clinically Important Difference
OT  - Responder Analyses
EDAT- 2019/07/07 06:00
MHDA- 2020/07/01 06:00
CRDT- 2019/07/07 06:00
PHST- 2018/07/20 00:00 [received]
PHST- 2019/04/22 00:00 [revised]
PHST- 2019/05/19 00:00 [accepted]
PHST- 2019/07/07 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2019/07/07 06:00 [entrez]
AID - S1743-6095(19)31216-0 [pii]
AID - 10.1016/j.jsxm.2019.05.012 [doi]
PST - ppublish
SO  - J Sex Med. 2019 Aug;16(8):1226-1235. doi: 10.1016/j.jsxm.2019.05.012. Epub 2019 
      Jul 2.