2. Study to Evaluate the Efficacy/Safety of Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder

Study Overview
=================
Brief Summary
-----------------
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial with an optional Open-label Extension to evaluate the efficacy of bremelanotide (BMT), administered subcutaneously (SC) on an as needed basis for the treatment of HSDD (with or without decreased arousal) in premenopausal females.

Detailed Description
-----------------
This will be a multicenter, randomized, placebo-controlled, parallel group study in up to 80 sites in the United States of America (USA) and Canada to evaluate the efficacy and safety of a fixed dose of SC BMT versus placebo on an as-needed basis under conditions of home use in premenopausal women with HSDD (with or without decreased arousal). The study will consist of 2 phases: (1) Core Study: 4-week no-treatment qualification period, a 4-week single-blind placebo treatment period (baseline), and a 24-week double-blind treatment period where participants will self-administer placebo or BMT 1.75 mg SC via an autoinjector; and (2) Extension Phase: a 52-week open-label treatment period during which all subjects will receive BMT 1.75 mg. Primary Objective • To evaluate the efficacy of bremelanotide (BMT), administered subcutaneously (SC) on an as needed basis for the treatment of HSDD (with or without decreased arousal) in premenopausal females. Secondary Objectives To evaluate the efficacy of BMT in premenopausal women in the double-blind Core Study, as assessed by subject responses to questionnaires measuring sexual function, treatment satisfaction, and distress associated with sexual dysfunction. To evaluate the safety of BMT in premenopausal women in the double-blind Core Study. To evaluate the safety of long-term therapy with BMT in the open label Extension Phase. To evaluate the efficacy of long-term therapy with BMT in the open-label Extension Phase.

Official Title
-----------------
Phase 3, Randomized, Double-blind, Placebo-controlled, Trial With an Open-label Extension Phase to Evaluate the Efficacy and Safety of Subcutaneously Bremelanotide in Premenopausal Women With Hypoactive Sexual Desire Disorder (HSDD)

Conditions
-----------------
Hypoactive Sexual Desire Disorder

Intervention / Treatment
-----------------
* Drug: Bremelanotide
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Has met diagnostic criteria for HSDD for at least 6 months Is willing and able to understand and comply with all study requirements Has a normal pelvic examination at screening Main Exclusion Criteria: Subjects should be generally healthy premenopausal females with no psychological, gynecological or urological conditions which might contribute to the sexual dysfunction, compromise study participation, or confound interpretation of the study results Not currently under treatment for the sexual dysfunction and willing to forego other treatments through the course of the clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bremelanotide (BMT/BMT)<br>(Main Study) Subjects will self-administer a fixed dose (1.75 mg) of bremelanotide (BMT) subcutaneously (SC) via auto-injector on an as needed basis with no more than 1 dose taken every 24 hours for 24 weeks (OLE Study) Subjects will self-administer a fixed dose (1.75 mg) of bremelanotide (BMT) subcutaneously (SC) via auto-injector on an as needed basis with no more than 1 dose taken every 24 hours for 52 weeks | Drug: Bremelanotide<br>* A melanocortin agonist and synthetic peptide analog of the naturally occurring hormone alpha-MSH (melanocyte-stimulating hormone)<br>* Other names: PT-141;|
| Placebo Comparator: Placebo (PBO/BMT)<br>(Main Study) PBO administered SC on an as-desired basis for 24 weeks (OLE Study) subjects will self-administer a fixed dose (1.75 mg) of bremelanotide (BMT) subcutaneously (SC) via auto-injector on an as needed basis with no more than 1 dose taken every 24 hours for 52 weeks | Drug: Bremelanotide<br>* A melanocortin agonist and synthetic peptide analog of the naturally occurring hormone alpha-MSH (melanocyte-stimulating hormone)<br>* Other names: PT-141;Drug: Placebo<br>* Placebo<br>* Other names: PBO;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of a Fixed Dose of Bremelanotide as Measured by FSFI (Question Q1 and Q2), 28-day Recall. | As measured by change from baseline to end-of-study in the desire domain from the FSFI (Question Q1 and Q2), 28-day recall, co-primary endpoint - FSFI desire domain This score is on a scale ranging from 1.2 to 6. A higher score on this scale represent an increase in sexual desire and is a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide as Measured by FSDS-DAO (Item 13) | As measured by the change from baseline to End-of-Study of the Core Study in the bothered by low desire item from the FSDS-DAO (item 13). Responses range from 0 (never) to 4 (always). Lower scores on this scale represent an increase in sexual desire and indicate a better outcome. Higher scores indicate a worse outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study (EOS) in the Number of Satisfying Sexual Events (SSEs) Associated With Study Drug Administration | Mean change from Baseline to end of study (EOS) in the number of satisfying sexual events (SSEs) that occurred within 16 hours of study drug dosing and reported within 72 hours. An increase in number indicates a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in Mean Desire Score (Q3) From the FSEP-R | FSEP-R=Female Sexual Encounter Profile - Revised Scores on this scale range from 0 (no desire) to 3 (high desire). Scale is derived from a questionnaire (mean desire score) where an increase in value indicates a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in Mean Satisfaction With Desire Score (Q4) From FSEP-R | FSEP-R=Female Sexual Encounter Profile - Revised Scores range from 0 (no desire) to 3 (high desire). Scale is derived from a questionnaire (mean desire score) where a higher score indicates a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the FSDS-DAO Total Score | FSDS-DAO = Female Sexual Distress Scale - Desire/Arousal/Orgasm. The FSDS-DAO is a validated 15-item self-assessment of sexual feelings and problems. All responses are on a scale ranging from 0 (never) to 4 (always). Total Scores range from 0 (never feel bothered) to 60 (always feel bothered). Decreased scores indicate improvement. A higher score on this scale indicates a worse outcome. The score is the mean change from Baseline observed at EOS (Baseline score - EOS score) | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the FSFI Total Score | Female Sexual Function Index (FSFI) The score is computed programmatically ] resulting in a score on a scale ranging from 1.2 to 6 (Note: OLE: Open-label extension. Scores range from 2 to 36. An improvement in total FSFI score is an increase from baseline. A higher score on this scale represents an increase in sexual desire and is a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Mean Level of Sexual Arousal (Q6) From the FSEP-R | FSEP-R=Female Sexual Encounter Profile - Revised Scores on this scale range from 0 (no desire) to 3 (high desire) Scale is derived from a questionnaire (mean desire score) where a higher score indicates a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Mean Satisfaction With Sexual Arousal (Q7) From the FSEP-R | FSEP-R=Female Sexual Encounter Profile - Revised Scores range from 0 (no desire) to 3 (high desire) Scale is derived from a questionnaire (mean desire score) where a higher score indicates a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Scored Time Spent Being Concerned by Difficulty With Sexual Arousal (Q14) From the FSDS-DAO | FSDS-DAO = Female Sexual Distress Scale - Desire/Arousal/Orgasm. The FSDS-DAO is a validated 15-item self-assessment of sexual feelings and problems. Scores on this scale range from 0 (never) to 4 (always). Decreased scores indicate improvement. A higher score on this scale indicates a worse outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Arousal Domain of the FSFI (Q3 to Q6) | Female Sexual Function Index (FSFI) The score is computed programmatically using the algorithm described by Rosen, resulting in a score ranging from 1.2 to 6. Higher scores on this scale represent an increase in sexual desire and is a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Total Number of SSEs | Change from Baseline to EOS in the total number of satisfying sexual events SSEs. A higher number of events indicates a better outcome. | 8 weeks baseline plus 24 weeks (Main Study), 52 Weeks (OLE) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Desire Domain of the FSFI (Q1 to Q2) Throughout the Entirety of the Double-blind Phase | FSFI = Female Sexual Function Index The score is on a scale ranging from 1.2 to 6. A higher score on this scale represents an increase in sexual desire and is a better outcome. | 24 weeks (Main Study) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Score for Feeling Bothered by Low Sexual Desire as Measured by the FSDS-DAO (Item 13) Throughout the Entirety of the Double-blind Phase | FSDS-DAO = Female Sexual Distress Scale - Desire/Arousal/Orgasm. The FSDS-DAO is a validated 15-item self-assessment of sexual feelings and problems. The score is on a scale ranging from 0 (never) to 4 (always). Decreased scores indicate improvement. A higher score indicates a worse outcome. | 24 weeks (Main Study) | 
| Efficacy of a Fixed Dose of Bremelanotide, as Measured by the Change in Baseline to End of Study in the Number of SSEs Associated With Study Drug Administration Throughout the Entirety of the Double-blind Phase | Mean change from Baseline to EOS in the number of satisfying sexual events SSEs associated with study drug administration throughout the entirety of the double-blind phase. A higher number of events indicates a better outcome. | 24 weeks (Main Study) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HSDD Female, Sexual Desire Disorder, decreased desire, female sexual dysfunction