Role of the Melanocortin-4 Receptor in Hypoactive Sexual Desire Disorder

NCT04179734 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 262886
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A randomised, double-blind, placebo-controlled, two-way crossover physiological study. Designed to evaluate the effects of melanocortin-4 receptor (MC4R) activation on brain activity patterns and behavioural psychometric measures of sexual arousal during visual erotic stimuli in approximately 40 right-handed, heterosexual, premenopausal women aged 18 years and over with Hypoactive Sexual Desire Disorder (HSDD) for at least a 6 month duration.

Conditions

Hypoactive Sexual Desire Disorder

Keywords

Hypoactive Sexual Desire Disorder; Bremelanotide; Functional MRI; Melanocortin-4 receptor

Outcome Measures

Primary Outcomes (1)

• Changes in Blood Oxygen Level Dependent (BOLD) Signal Change on Functional MRI

  Blood Oxygen Level Dependent (BOLD) imaging was used to detect activation clusters within the brain. Units of measure were standardised regression coefficients derived from the regression analysis that were used to fit the analysis model to the time-series data (BOLD signal change). Higher BOLD signal change values indicate increased activation in particular areas of the brain in response to the intervention (Bremelanotide or Placebo).

  Baseline and 15 minutes

Study Arms (2)

Intervention

EXPERIMENTAL

Bremelanotide 1.75 mg - prefilled subcutaneous autoinjector containing 1.75 mg Bremelanotide in a 0.3 mL solution volume.

Drug: Bremelanotide; Drug: Placebo

Placebo

PLACEBO COMPARATOR

1.75 mg equivalent - prefilled subcutaneous autoinjector containing Bremelanotide formulation without the active ingredient in a 0.3 mL solution volume.

Drug: Bremelanotide; Drug: Placebo

Interventions

Bremelanotide DRUG

Melanocortin-4 receptor agonist subcutaneous injection.

Intervention; Placebo

Placebo DRUG

Placebo subcutaenous injection.

Intervention; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heterosexual premenopausal females ≥ 18 years of age with normal menstrual cycles ≤ 35 days.
• Right hand dominant.
• Body mass index (BMI) 18-35kg/m2.
• Currently in a relationship with a male partner and the relationship has been stable for at least 6 months before screening.
• Male sexual partner classified as "not impotent" on the Massachusetts Male Aging Study (MMAS) single-question assessment of erectile dysfunction.
• In the subject's opinion, previously experienced "normal sexual function," defined as a normal level of desire at some point in the past, for a period of at least 2 years.
• For all subjects of childbearing potential who are sexually active, agree to routinely use adequate non-hormonal contraception from randomisation throughout the duration of the study and for 30 days after.
• For at least 6 months before Screening, met the diagnostic criteria for HSDD according to the Diagnostic Screening Guide for HSDD, including categorisation of the sexual dysfunction as both acquired (versus lifelong) and generalised (versus situational).
• All of the following at Screening:
• Patient Health Questionnaire (PHQ-9) (Kroenke et al., 2001) total score is \<10.
• PHQ-9 score for Question 9 is 0.
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• Either Female Sexual Function Index (FSFI) total score ≤26 if diagnosed with HSDD (with or without symptoms of decreased arousal) or subjects diagnosed with HSDD only (without symptoms of decreased arousal), FSFI desire domain score of ≤5 (regardless of total FSFI score).
• Female Sexual Distress Scale - Desire/Arousal/Orgasm (FSDS-DAO) total score is \>18.
• Capable of understanding and complying with the protocol requirements and available for the duration of the study.

You may not qualify if:

• Cardiovascular disease
• Current diagnosis of uncontrolled hypertension defined as:
• Two sequential assessments (seated, approximately 4 minutes apart and no more than 15 minutes apart) with readings above 140 mmHg systolic BP or 90 mmHg diastolic BP, and upon repeat at least 24 hours later.
• Treatment for hypertension that has been changed at least once in the 4 weeks prior to Screening.
• Any other medical condition that is unstable or uncontrolled despite current therapy.
• Previously received Bremelanotide.
• A history of unresolved sexual trauma or abuse.
• Female subjects who are pregnant, intend to become pregnant, are breastfeeding, have a positive serum/urine pregnancy test, or are not willing to use effective contraceptive precautions during the study.
• Participated in any research study within the preceding 30 days of screening.
• Any FSD other than acquired HSDD with or without decreased arousal (e.g. lifelong anorgasmia, sexual pain disorder, sexual aversion disorder, primary female sexual arousal disorder).
• FSD caused by untreated endocrine disease (e.g. hypopituitarism, hypothyroidism, diabetes mellitus).
• Acute or chronic hepatitis.
• In the Investigator's opinion, any urologic or gynecologic condition, such as condyloma, uterine fibroids, vulvar or vaginal lesions, vulvodynia, vaginismus, or pelvic pain that may contribute to impaired sexual activity and function or be a cause of the FSD or that may interfere with the subject's ability to comply with study procedures.
• Receiving any treatment for HSDD (e.g. psychotherapy, physical therapy) at the time of Screening.
• Has used any of the following types of medications, which are prohibited during the study:

Sponsors & Collaborators

• Imperial College Healthcare NHS Trust: lead
• AMAG Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Related Publications (9)

• Arnow BA, Millheiser L, Garrett A, Lake Polan M, Glover GH, Hill KR, Lightbody A, Watson C, Banner L, Smart T, Buchanan T, Desmond JE. Women with hypoactive sexual desire disorder compared to normal females: a functional magnetic resonance imaging study. Neuroscience. 2009 Jan 23;158(2):484-502. doi: 10.1016/j.neuroscience.2008.09.044. Epub 2008 Oct 2.

  PMID: 18976696 BACKGROUND

• Bianchi-Demicheli F, Cojan Y, Waber L, Recordon N, Vuilleumier P, Ortigue S. Neural bases of hypoactive sexual desire disorder in women: an event-related FMRI study. J Sex Med. 2011 Sep;8(9):2546-59. doi: 10.1111/j.1743-6109.2011.02376.x. Epub 2011 Jun 30.

  PMID: 21718449 BACKGROUND

• Pfaus JG, Shadiack A, Van Soest T, Tse M, Molinoff P. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10201-4. doi: 10.1073/pnas.0400491101. Epub 2004 Jun 28.

  PMID: 15226502 BACKGROUND

• Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Sexual problems and distress in United States women: prevalence and correlates. Obstet Gynecol. 2008 Nov;112(5):970-8. doi: 10.1097/AOG.0b013e3181898cdb.

  PMID: 18978095 BACKGROUND

• Murphy K, Garavan H. An empirical investigation into the number of subjects required for an event-related fMRI study. Neuroimage. 2004 Jun;22(2):879-85. doi: 10.1016/j.neuroimage.2004.02.005.

  PMID: 15193618 BACKGROUND

• Wikberg JE, Muceniece R, Mandrika I, Prusis P, Lindblom J, Post C, Skottner A. New aspects on the melanocortins and their receptors. Pharmacol Res. 2000 Nov;42(5):393-420. doi: 10.1006/phrs.2000.0725.

  PMID: 11023702 BACKGROUND

• Woodard TL, Nowak NT, Balon R, Tancer M, Diamond MP. Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study. Fertil Steril. 2013 Oct;100(4):1068-76. doi: 10.1016/j.fertnstert.2013.05.041. Epub 2013 Jul 2.

  PMID: 23830149 BACKGROUND

• Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019 Nov;134(5):899-908. doi: 10.1097/AOG.0000000000003500.

  PMID: 31599840 BACKGROUND

• Thurston L, Hunjan T, Mills EG, Wall MB, Ertl N, Phylactou M, Muzi B, Patel B, Alexander EC, Suladze S, Modi M, Eng PC, Bassett PA, Abbara A, Goldmeier D, Comninos AN, Dhillo WS. Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder. J Clin Invest. 2022 Oct 3;132(19):e152341. doi: 10.1172/JCI152341.

  PMID: 36189794 RESULT

MeSH Terms

Conditions

Sexual Dysfunctions, Psychological

Interventions

bremelanotide

Condition Hierarchy (Ancestors)

Mental Disorders

Results Point of Contact

• Title: Professor Waljit S. Dhillo, Principal Investigator
• Organization: Imperial College London

w.dhillo@imperial.ac.uk

00442075943487

Study Officials

• Waljit S Dhillo, MBBS PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 27, 2019
• Study Start: October 7, 2019
• Primary Completion: October 6, 2020
• Study Completion: October 6, 2020
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)