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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Female Sexual Arousal Disorder, Hypoactive Sexual Desire Disorder

Intervention / Treatment
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* Drug: bremelanotide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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<br>* 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.<br>* Other names: PT-141;|
| Experimental: bremelanotide arm 1<br>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<br>* 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.<br>* Other names: PT-141;|
| Experimental: bremelanotide arm 2<br>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<br>* 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.<br>* Other names: PT-141;|
| Experimental: bremelanotide arm 3<br>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<br>* 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.<br>* Other names: PT-141;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FSAD, HSDD, female sexual dysfunction, FSD, Female Sexual Arousal Disorder, Hypoactive Sexual Desire Disorder