Study to Evaluate Rate of Nausea in Healthy Premenopausal Female Subjects Treated With Single Dose of Bremelanotide Alone or With Zofran

• ClinicalTrials.gov Identifier: NCT03973047
• Recruitment Status: Completed
• First Posted: June 4, 2019
• Last Update Posted: July 17, 2020
• Sponsor: AMAG Pharmaceuticals, Inc.
• Information provided by (Responsible Party): AMAG Pharmaceuticals, Inc.

Study Description

Brief Summary:

This is a Phase 1, randomized study to evaluate the rate of nausea in healthy premenopausal study participants following a single dose of BMT with or without a single 8 mg po dose of Zofran given 30 minutes before BMT dosing.

Condition or disease	Intervention/treatment	Phase
Nausea	Drug: Bremelanotide; Drug: Zofran; Drug: Placebo	Phase 1

Detailed Description:

This is a Phase 1, randomized study to evaluate the rate of nausea in healthy premenopausal study participants following a single dose of BMT with or without a single 8 mg po dose of Zofran given 30 minutes before BMT dosing. The study consists of a 21-day screening period for subject eligibility followed by a 1-day double-blind period in which all subjects receive a single open-label dose of 1.75 mg SC BMT after receiving a single blinded dose of Zofran (ondansetron) 8 mg or placebo. Approximately 228 subjects will be enrolled at up to two study sites in the United States. Safety and tolerability of BMT administration will be summarized and assessed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: BMT will be administered in an open-label manner. Administration of Zofran or placebo will be double-blinded using an over-encapsulation (OE) technique . The randomization assignments and code will not be provided to the Sponsor, sites, or subjects until the study database has been locked, except as unblinding is required for non-study personnel in the regulatory reporting of serious adverse events (SAEs) or for other safety-related reasons.
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized Study to Evaluate the Rate of Nausea in Healthy Premenopausal Female Subjects Treated With a Single Dose of Bremelanotide Alone or With Zofran
• Actual Study Start Date: June 17, 2019
• Actual Primary Completion Date: July 19, 2019
• Actual Study Completion Date: July 20, 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Group 1: BMT plus placebo; 1 dose of BMT 1.75 mg via autoinjector plus placebo (dosed 30±5 minutes prior to BMT dosing) on Day 1.	Drug: Bremelanotide; Sterile aqueous solution for injection, provided as an autoinjector pen; Other Name: BMT; Drug: Placebo; capsule
Active Comparator: Group 2: BMT plus Zofran; 1 dose of BMT 1.75 mg via autoinjector plus Zofran 8 mg (dosed 30±5 minutes prior to BMT dosing) on Day 1.	Drug: Bremelanotide; Sterile aqueous solution for injection, provided as an autoinjector pen; Other Name: BMT; Drug: Zofran; 8 mg tablet (over-encapsulation in a capsule); Other Name: ondansetron

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent nausea following BMT with or without concomitant use of Zofran. [ Time Frame: 2 Days ]
   Incidence of treatment-emergent nausea following a single dose of BMT 1.75 mg SC with or without concomitant use of Zofran.

Secondary Outcome Measures :

1. Severity of nausea using a Visual Analog Scale [ Time Frame: 2 Days ]
   "Severity of Nausea Visual Analog Scale", where the range is 0 to 100 and a lower value represents a better outcome
2. Time to onset of nausea [ Time Frame: 2 Days ]
   The time to onset of nausea
3. Duration of nausea [ Time Frame: 2 Days ]
   The duration of nausea

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

Key Inclusion Criteria:

1. Willing and able to provide written informed consent prior to participating in the study.
2. Female subjects ≥18 to 55 years of age (inclusive) and premenopausal as defined by the modified STRAW criteria (specifically, Stage -5 [menses variable to regular] through Stage 1 [≥2 skipped cycles and an interval of amenorrhea ≥60 days]).
3. Able to communicate clearly with the Principle Investigator (PI) and staff; able to read English, complete questionnaires, and understand study procedures.
4. Able to complete all screening period evaluations, stay in the clinic testing facility for minimum of 4 hours following dose of BMT.
5. In good general health, free from clinically significant medical or psychiatric illness or disease (as determined by medical/surgical history, physical examination, weight, 12-lead ECG, and clinical laboratory tests).

Key Exclusion Criteria:

1. Postmenopausal female, designated by having amenorrhea for ≥12 months.
2. Has current or recent (within 6 months) history of gastrointestinal disease, or any surgical or medical condition such as Crohn's disease or liver disease, that could potentially alter the absorption, metabolism, or excretion of the study drug.
3. Has any clinically significant medical condition, physical exam finding, or ECG abnormality, or clinically significant abnormal value for hematology, serology, clinical chemistry, or urinalysis at Screening, or at admission to the study center, as assessed by the PI.

4. Has any of the following:

   - History or current diagnosis of uncontrolled hypertension defined as: Two (2) sequential assessments (at least 5 minutes apart and no more than 15 minutes apart) at levels >140 mmHg SBP or 90 mmHg DBP and/or treatment for hypertension that has been changed at least once in the 4 weeks before Screening.

   - Renal dysfunction (creatinine clearance < 80 mL/min using Cockcroft Gault calculation).

5. History or presence of malignancy within the past 5 years, with the exception of adequately treated localized skin cancer (basal cell or squamous cell carcinoma), which is allowed.

Contacts and Locations

Locations

United States, Texas

ICON Early Phase Serrvices, LLC

San Antonio, Texas, United States, 78209

Sponsors and Collaborators

AMAG Pharmaceuticals, Inc.

More Information

• Responsible Party: AMAG Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03973047
• Other Study ID Numbers: AMAG-BMT-HSDD-102
• First Posted: June 4, 2019
• Last Update Posted: July 17, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AMAG Pharmaceuticals, Inc.:

Nausea; Bremelanotide; BMT; Zofran; ondansetron; premenopausal; healthy women

Additional relevant MeSH terms:

Nausea; Signs and Symptoms, Digestive; Ondansetron; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipruritics; Dermatologic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Anti-Anxiety Agents