Dataset Information

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.

ABSTRACT:

Aim

Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women.

Methods

Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm.

Results

Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), -11.1 versus -6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache.

Conclusion

In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719).

SUBMITTER: Clayton AH

PROVIDER: S-EPMC5384512 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.

Clayton Anita H AH Althof Stanley E SE Kingsberg Sheryl S DeRogatis Leonard R LR Kroll Robin R Goldstein Irwin I Kaminetsky Jed J Spana Carl C Lucas Johna J Jordan Robert R Portman David J DJ

Women's health (London, England) 20160516 3

<h4>Aim</h4>Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women.<h4>Methods</h4>Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm ...[more]

PMID: 27181790

Similar Datasets

Project description:BackgroundThe symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB?MethodsIn our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data.Trial registrationClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects.InterpretationOur adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation.FundingUK MRC DCS/DPFS grant MR/J003611/1.

Project description:IntroductionHeavy menstrual bleeding (HMB) diminishes individual quality-of-life and poses substantial societal burden. In HMB endometrium, inactivation of cortisol (by enzyme 11β hydroxysteroid dehydrogenase type 2 (11βHSD2)), may cause local endometrial glucocorticoid deficiency and hence increased angiogenesis and impaired vasoconstriction. We propose that 'rescue' of luteal phase endometrial glucocorticoid deficiency could reduce menstrual bleeding.Methods and analysisDexFEM is a double-blind response-adaptive parallel-group placebo-controlled trial in women with HMB (108 to be randomised), with active treatment the potent oral synthetic glucocorticoid dexamethasone, which is relatively resistant to 11βHSD2 inactivation. Participants will be aged over 18 years, with mean measured menstrual blood loss (MBL) for two screening cycles ≥50 mL. The primary outcome is reduction in MBL from screening. Secondary end points are questionnaire assessments of treatment effect and acceptability. Treatment will be for 5 days in the mid-luteal phases of three treatment menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg twice daily) will be compared with placebo, to ascertain optimal dose, and whether this has advantage over placebo. Statistical efficiency is maximised by allowing randomisation probabilities to 'adapt' at five points during enrolment phase, based on the response data available so far, to favour doses expected to provide greatest additional information on the dose-response. Bayesian Normal Dynamic Linear Modelling, with baseline MBL included as covariate, will determine optimal dose (re reduction in MBL). Secondary end points will be analysed using generalised dynamic linear models. For each dose for all end points, a 95% credible interval will be calculated for effect versus placebo.Ethics and disseminationDexamethasone is widely used and hence well-characterised safety-wise. Ethical approval has been obtained from Scotland A Research Ethics Committee (12/SS/0147). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures, and our websites.Trial registration numberClinicalTrials.gov NCT01769820; EudractCT 2012-003405-98.

Dataset Information

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.

Aim

Methods

Results

Conclusion

Publications

Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets