Bremelanotide in Premenopausal Women With Female Sexual Arousal Disorder and/or Hypoactive Sexual Desire Disorder

A Placebo-controlled, Randomized, Parallel Group, Dose-finding Trial to Evaluate the Efficacy and Safety of Subcutaneously Administered Bremelanotide in Premenopausal Women With FSAD (Female Sexual Arousal Disorder) and/or HSDD (Hypoactive Sexual Desire Disorder)

This trial is designed to evaluate the efficacy and safety of 3 fixed dose levels of bremelanotide, administered subcutaneously on an as-needed basis under conditions of home use, for the treatment of female sexual arousal disorder (FSAD), hypoactive sexual desire disorder (HSDD), or mixed FSAD/HSDD in premenopausal women.

Study Overview

• Status: Completed
• Conditions: Hypoactive Sexual Desire Disorder; Female Sexual Arousal Disorder
• Intervention / Treatment: Drug: bremelanotide

• Study Type: Interventional
• Enrollment (Actual): 612
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • North Vancouver, British Columbia, Canada, V7N 2H5
      • Site 4
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Site 41
    • Burlington, Ontario, Canada, L7R4G1
      • Site 21
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Site 56
    • Huntsville, Alabama, United States, 35801
      • Site 26
    • Mobile, Alabama, United States, 36608
      • Site 64
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Site 45
    • Phoenix, Arizona, United States, 85032
      • Site 39
    • Tucson, Arizona, United States, 85712
      • Site 25
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Site 78
    • Jonesboro, Arkansas, United States, 72401
      • Site 16
  • California
    • National City, California, United States, 91950
      • Site 52
    • Newport Beach, California, United States, 92880
      • Site 73
    • Sacramento, California, United States, 95821
      • Site 80
    • San Diego, California, United States, 92120
      • Site 12
  • Colorado
    • Denver, Colorado, United States, 80218
      • Site 37
    • Lakewood, Colorado, United States, 80228
      • Site 40
  • Connecticut
    • Avon, Connecticut, United States, 06117
      • Site 8
    • Farmington, Connecticut, United States, 06032
      • Site 75
    • New London, Connecticut, United States, 06320
      • Site 33
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Site 32
  • Florida
    • Aventura, Florida, United States, 33180
      • Site 10
    • Fort Myers, Florida, United States, 33916
      • Site 27
    • Melbourne, Florida, United States, 32935
      • Site 66
    • Orlando, Florida, United States, 32806
      • Site 61
    • West Palm Beach, Florida, United States, 33401
      • Site 1
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Site 82
    • Decatur, Georgia, United States, 30030
      • Site 55
  • Illinois
    • Chicago, Illinois, United States, 60654
      • Site 70
    • Peoria, Illinois, United States, 61602
      • Site 54
  • Indiana
    • South Bend, Indiana, United States, 46545
      • Site 63
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Site 13
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Site 48
  • Louisiana
    • Zachary, Louisiana, United States, 70791
      • Site 57
  • Maryland
    • Baltimore, Maryland, United States, 21093
      • Site 9
    • Rockville, Maryland, United States, 20850
      • Site 60
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Site 74
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Site 35
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Site 72
    • Las Vegas, Nevada, United States, 89128
      • Site 24
  • New York
    • New York, New York, United States, 10016
      • Site 18
    • Purchase, New York, United States, 10577
      • Site 38
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Site 3
    • Winston-Salem, North Carolina, United States, 27103
      • Site 47
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Site 23
    • Canton, Ohio, United States, 44718
      • Site 69
    • Cincinnati, Ohio, United States, 45249
      • Site 71
    • Cleveland, Ohio, United States, 44124
      • Site 19
    • Columbus, Ohio, United States, 43213
      • Site 30
    • Englewood, Ohio, United States, 45322
      • Site 81
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Site 2
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Site 42
    • Pittsburgh, Pennsylvania, United States, 15206
      • Site 77
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Site 43
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Site 58
    • Mt. Pleasant, South Carolina, United States, 29464
      • Site 49
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Site 53
  • Texas
    • Corpus Christi, Texas, United States, 78414
      • Site 59
    • Dallas, Texas, United States, 75231
      • Site 76
    • Dallas, Texas, United States, 75234
      • Site 31
    • Houston, Texas, United States, 77054
      • Site 17
    • San Antonio, Texas, United States, 78229
      • Site 62
  • Utah
    • Murray, Utah, United States, 84123
      • Site 50
    • Sandy, Utah, United States, 84070
      • Site 36
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Site 7
    • Norfolk, Virginia, United States, 23502
      • Site 68
    • Richmond, Virginia, United States, 23294
      • Site 65
  • Washington
    • Seattle, Washington, United States, 98105
      • Site 22

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Female, at least 21 years of age, and premenopausal Previously experienced sexual arousal during sexual activity and/or normal level of desire in the past for least 2 years.

Willing to engage in sexual activities Currently in stable relationship with a partner(male or female)for at least 6 months.

If subject has a male sexual partner, has recorded a score of "not impotent" or "minimally impotent" on Single-question Assessment of ED.

For at least 6 months before Screening, has met diagnostic criteria for FSAD, HSDD, or mixed FSAD/HSDD Has a negative serum pregnancy test (hCG) at Screening and, if subject's partner is male, has used a medically acceptable form of contraception for the 3 months before Screening (Visit 1), and is willing to continue for the duration of the trial and 1 month following the last dose of trial drug.

Has a normal pelvic examination. At Screening or documented within 12 months before Screening, has:normal Pap test results with or without history of positive HPV, dysplasia, or ASCUS that has resolved or been treated;Pap test results positive for ASCUS and negative for HPV;Pap test results positive for HPV AND no ASCUS or dysplasia on Pap or condyloma present upon examination.

At Screening and Visit 2, meets all necessary questionnaire scores.

Exclusion Criteria:

Medical condition that is unstable or uncontrolled despite current therapy. History of unresolved sexual trauma or abuse. Pregnant or nursing. Lifelong anorgasmia, vaginismus, sexual pain disorder, sexual aversion disorder, or persistent sexual arousal disorder.

Female sexual dysfunction caused by untreated endocrine disease. Has or has had any of the following: hepatitis C, other infectious hepatitis, infectious blood disorders such as HIV; myocardial infarction;stroke.

Has or has had any of the following within 12 months before Screening:chronic dyspareunia not attributable to vaginal dryness; pelvic inflammatory disease; chronic or complicated UTI, or an active STD other than herpes and condyloma; cervical dysplasia, including LGSIL and HGSIL and/or ASCUS with HPV; significant cervicitis as manifested by mucopurulent discharge from the cervix.

Has had any of the following within 6 months before Screening:≥ 2 outbreaks of genital herpes; occurrence/recurrence of clinically significant condyloma;clinically unstable angina or clinically unstable arrhythmia;significant CNS diseases;AST or ALT concentrations > 3 times the ULN;serum creatinine > 2.5 mg/dL;any other clinically significant abnormal laboratory result.

Has used prohibited medications within the 3 months before Screening:

Has currently active moderate to severe vaginitis or a clinically significant vaginal infection.

Has one or more significant gynecologic conditions . Is taking or has received treatment for psychosis, bipolar disorder, depression, and/or alcohol/substance abuse within 6 months before Screening.

Is currently receiving psychotherapy for the treatment of FSAD and/or HSDD. Has any of the following: Uncontrolled hypertension;Systolic BP of ≥ 140 mm Hg at Screening;Diastolic BP of ≥ 90 mm Hg at Screening; Treatment for hypertension that has changed in the 3 months before Screening.

Had a hysterectomy with bilateral oophorectomy. Had a hysterectomy without bilateral oophorectomy AND meets several other criteria.

Is taking contraceptives that have affected the menstrual cycle or caused amenorrhea AND did not have a normal menstrual cycle before starting the contraceptive medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Same formulation as the investigation product but without the active ingredient, provided as pre-filled syringes containing 0.3 mL volume. Subjects will self-administer the placebo by SC injection in the same manner as the investigational product.	Drug: bremelanotide; Subjects will administer drug on an as needed basis, prior to anticipated sexual activity. Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 0.75, 1.25, or 1.75 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen. Placebo: Same formulation as the investigation product but without the active ingredient, provided as pre-filled syringes containing 0.3 mL volume. Subjects will self-administer the placebo by SC injection in the same manner as the investigational product.; Other Names: PT-141
Experimental: bremelanotide arm 1; Low dose: Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 0.75 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen.	Drug: bremelanotide; Subjects will administer drug on an as needed basis, prior to anticipated sexual activity. Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 0.75, 1.25, or 1.75 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen. Placebo: Same formulation as the investigation product but without the active ingredient, provided as pre-filled syringes containing 0.3 mL volume. Subjects will self-administer the placebo by SC injection in the same manner as the investigational product.; Other Names: PT-141
Experimental: bremelanotide arm 2; Middle dose: Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 1.25 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen.	Drug: bremelanotide; Subjects will administer drug on an as needed basis, prior to anticipated sexual activity. Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 0.75, 1.25, or 1.75 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen. Placebo: Same formulation as the investigation product but without the active ingredient, provided as pre-filled syringes containing 0.3 mL volume. Subjects will self-administer the placebo by SC injection in the same manner as the investigational product.; Other Names: PT-141
Experimental: bremelanotide arm 3; High dose: Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 1.75 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen.	Drug: bremelanotide; Subjects will administer drug on an as needed basis, prior to anticipated sexual activity. Investigational product: Bremelanotide aqueous solution for subcutaneous (SC) injection, provided as pre-filled syringes containing 0.75, 1.25, or 1.75 mg in 0.3 mL volume. Subjects will self-administer bremelanotide by SC injection into the anterior thigh or abdomen. Placebo: Same formulation as the investigation product but without the active ingredient, provided as pre-filled syringes containing 0.3 mL volume. Subjects will self-administer the placebo by SC injection in the same manner as the investigational product.; Other Names: PT-141

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Efficacy Endpoint is Change From Baseline to End of Study in the Number of Satisfying Sexual Events (SSE)	The primary efficacy endpoint is change from baseline to end of study in the number of satisfying sexual events (SSEs), computed as the number of events during the last 4 weeks of treatment with FSEP-R Q10 = "Yes" minus the number of baseline events with FSEP-R Q10 = "Yes." Efficacy analyses were done with the MITT population which consisted of all randomized subjects who took at least 1 dose of double-blind treatment after the 2 in-clinic doses of double-blind medication and who had at least 1 follow-up visit (Visit 10 or later) to ensure that FSEP-R data were reviewed and confirmed by the investigative site.	4 - 12 weeks from baseline to end of study (total study duration 20 weeks). Baseline was the 4-week single-blind placebo period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to End-of-Study in Arousal Domain Score From Female Sexual Function Index	The FSFI is brief self-report questionnaire that measures female sexual function. The change from baseline to end of study in the arousal domain were obtained from the FSFI Q3 through Q6. The score range is 0-5. For each of the 2 time points, the score was computed programmatically using the algorithm described by Rosen [6], resulting in a score from 0 (min) to 6 (max).	4-12 weeks from baseline to end of study (total study duration 20 weeks)
Satisfaction With Arousal as Measured by GAQ Question 1	This is the change in Baseline to End-of-Study in Satisfaction with Arousal as measured by GAQ Question 1. GAQ (Global Assessment Questions) is a questionnaire that evaluates overall satisfaction level experienced while using the study drug. Question 1 is "Compared to the start of the study (prior to taking the study drug), how would you describe your satisfaction with your arousal while using the study drug?" The score range is 1 (very much worse) to 7 (very much better).	4-12 weeks from baseline to end of study (total study duration 20 weeks)
Desire Domain From Female Sexual Function Index	The FSFI is brief self-report questionnaire that measures female sexual function. The change from baseline to end of study in the desire domain were obtained from the FSFI Q1 and Q2. The score range is 1-5. For each of the 2 time points, the score was computed programmatically using the algorithm described by Rosen [6], resulting in a score from 0 (min) to 6 (max).	4-12 weeks from baseline to end of study (total study duration 20 weeks)
Satisfaction With Desire as Measured by GAQ Question 2	This is the change in Baseline to End-of-Study in Satisfaction with Desire as Measured by GAQ Question 2. GAQ (Global Assessment Questions) is a questionnaire that evaluates overall satisfaction level experienced while using the study drug. Question 2 is "Compared to the start of the study (prior to taking the study drug), how would you describe your satisfaction with your desire while using the study drug?" The score range is 1 (very much worse) to 7 (very much better).	4-12 weeks from baseline to end of study (total study duration 20 weeks)
Quality of Relationship With Partner as Measured by GAQ Question 4	This is the change in Baseline to End-of-Study in Quality of Relationship with Partner as Measured by GAQ Question 4. GAQ (Global Assessment Questions) is a questionnaire that evaluates overall satisfaction level experienced while using the study drug. Question 4 is "Compared to the start of the study (prior to taking the study drug), how has taking the study drug changed your relationship with your partner?" The score range is 1 (very much worse) to 7 (very much better).	4-12 weeks from baseline to end of study (total study duration 20 weeks)
FSDS-DAO Total Score	FSDS-DAO (Female Sexual Distress Scale - Desire/Arousal/Orgasm) is an assessment tool to measure female sexual distress. The change from baseline to end of study in the FSDS-DAO (total score) was measured. There are 15 questions, eg, "How often do you feel: Distressed about your sex life" and the score range was 0 (Never), 1 (Rarely), 2 (Occasionally), 3 (Frequently), 4 (Always). The score for each subject at each time point was computed as the sum of the scores from the 15 questions, resulting in a possible score at each time point between 0 and 60.	4 - 12 weeks from baseline to end of study (total study duration 20 weeks)

Collaborators and Investigators

• Sponsor: Palatin Technologies, Inc
• Investigators: Study Director: Jeffrey Edelson, MD, FRCPC, Palatin Technologies, Inc

Publications and helpful links

General Publications

• Derogatis LR, Revicki DA, Rosen RC, Jordan R, Lucas J, Spana C. Psychometric validation of the Female Sexual Distress Scale-Desire/Arousal/Orgasm. J Patient Rep Outcomes. 2021 Sep 24;5(1):100. doi: 10.1186/s41687-021-00359-1.
• Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, Spana C, Lucas J, Jordan R, Portman DJ. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond). 2016 Jun;12(3):325-37. doi: 10.2217/whe-2016-0018. Epub 2016 May 16.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 24, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): December 18, 2014
• Last Update Submitted That Met QC Criteria: December 2, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: HSDD; female sexual dysfunction; Hypoactive Sexual Desire Disorder; Female Sexual Arousal Disorder; FSD; FSAD
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Disease; Hypokinesia; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological
• Other Study ID Numbers: PT-141-54