A Phase 2 Study Evaluating the Co-Administration of Bremelanotide with Tirzepatide for the Treatment of Obesity (BMT-801)

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Clinical Study Investigating the Safety, Tolerability, and Effectiveness of the Co-Administration of Bremelanotide with Tirzepatide (GLP-1/GIP) for the Treatment of Obesity

This is a prospective, randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of bremelanotide (BMT) used in combination with tirzepatide therapy in the treatment of obesity in subjects with a BMI ranging from 30.0 to 45.0 kg/m2 (inclusive).

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: bremelanotide; Drug: tirzepatide

Detailed Description

A total of approximately 108 subjects at approximately five (5) centers within the United States (US), will be enrolled into the study for 8 weeks of treatment. Subjects who provide written informed consent and meet all initial eligibility criteria will enter into Screening. The subjects' historical and current medical data will be collected, reviewed, and recorded to be used as baseline values.

Enrolled subjects will begin the study and go through 2 treatment periods:

• "Treatment Period 1" - 4 weeks of tirzepatide therapy only
• "Treatment Period 2" - 4 weeks of combination therapy of bremelanotide, Placebo, or tirzepatide therapy.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • University Clinical Research-DeLand LLC, d/b/a Accel Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • South Carolina
    • North Charleston, South Carolina, United States, 29405-5093
      • Coastal Carolina Research Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Lynn Institute of Chattanooga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged between 18-65 years of age, inclusive at the time of consent.
2. Have a body mass index (BMI) of 30.0 to 45.0 kg/m^2 (inclusive) at screening.

3. Female subjects must have a negative urine pregnancy test at screening, if of childbearing potential or be of non-childbearing potential. If the urine test is positive or cannot be confirmed as negative, then the subject must have a negative serum pregnancy test (hCG). Non-childbearing potential is defined as (by other than medical reasons):

   1. Age ≥ 50 years, no menses for at least one year, per subject self-report.
   2. Documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy.

4. For female subjects who are Women of childbearing potential (WOCBP), subject must agree to abstain from heterosexual intercourse or use a highly effective contraceptive(s) (with a failure rate of <1% per year), as described in the protocol, during the treatment and follow-up and for at least 90 days after the last dose of bremelanotide. Hormonal-based contraception is to be employed for a minimum of 28 days prior to Day 0. Oral hormonal contraceptives should be combined estrogen and progesterone. If a progesterone-only oral contraceptive is used, then a second method of birth control should be used as well. Acceptable forms of contraception include:

   • Surgical sterilization of the subject or male partner;
   • FDA- or Health Canada-approved female hormonal contraceptives;
   • An IUD;
   • Essure® (transcervical sterilization);

   • "Double-barrier" contraception defined as:

     • condom + spermicide, or
     • condom + diaphragm (which is used with a spermicide).
5. Female subjects must agree not to donate eggs (ova, oocytes) for any purpose during the treatment and follow-up and for at least 30 days after the last dose of BMT.

6. Male subjects must agree to abstain from heterosexual intercourse or use double barrier protection with condom and spermicide with any WOCBP sexual partner from screening and continuing for at least 30 days after the last dose of BMT:

   a. Alternatively, documented sterilization confirmed by the absence of sperm in the ejaculate or ≥ one-year post-operative from vasectomy.

7. Male subjects must agree not to donate sperm for at least 30 days after the last dose of BMT.
8. Subjects must be willing to self-inject.
9. Subjects must have the ability to complete the study in compliance with the protocol and all instructions.
10. Subjects must have the ability to understand and provide written informed consent.

Exclusion Criteria:

1. Females who are pregnant, breastfeeding or plan to become pregnant.
2. Have a known allergy or intolerance to Melanocortin peptides.

3. Subjects with a positive Serum Antigen/Antibody Hepatitis Panel (Hep B and C) and HIV antibody test Human Immunodeficiency Virus (HIV) antibody.

   Note: subject with positive hepatitis C antibody but negative PCR test for active Hepatitis C viral shedding will be allowed to participate in the study. Subjects with a positive Hepatitis B surface antigen antibody or core antigen antibody will be allowed to participate in the study. Subjects with circulating hepatitis B surface antigen or have a positive PCR test for active hepatitis B virus will NOT be allowed to participate in the study.

4. Subjects with active alcohol dependence and/or drug use (with Cannabis exception) as assessed by the Investigator will be excluded from the study.
5. Have significant medical illnesses that cannot be adequately controlled with appropriate therapy and may obscure toxicity, dangerously alter drug metabolism, or compromise the subject's ability to participate in the trial, as determined by the Investigator, such as endocrinologic disorders accounting for obesity such as Cushing Disease, syndrome or monogenic obesity and exclusions of organ transplant recipients, those on wait lists, or those on anti-rejection medication as the potential effect on gastric emptying effecting pharmacokinetics.
6. Has been on bremelanotide therapy (Vyleesi) within the past 6 months prior to screening date.
7. Within the past three month, has used cyclosporine A, adrenocorticotropic hormones, long-term corticosteroids (> 20 mg qd or its equivalent for > 3 months), or cytotoxic agents.
8. Has had clinically significant body weight change (≥5%) or dieting attempts in the prior 90 days (per subject reported information) and Treatment Period 1.
9. Use of Anti-Obesity Medication (AOM) within a 90-day period prior to screening (Note: subjects who have taken or are still taking tirzepatide may participate in study if exclusion criteria #8 has not been met. AOM medications will also include medications that are being used off-label for weight loss).
10. Prior obesity or weight loss surgery or presence of gastrointestinal implant or bariatric surgery or other weight loss procedures within 2 years of screening (i.e. liposuction, abdominoplasty, intragastric balloon, cholecystectomy, etc.)
11. Has HbA1c ≥ 6.5 % or fasting glucose ≥126.0 mg/dL. (either test can be used to establish eligibility).
12. Has type 1 diabetes.
13. Has taken any experimental drug or therapy within 28 days / 5 half-lives of trial treatment or concurrently participating in another clinical trial.
14. Has a history of clinically significant bradycardia and/or a heart rate less than 50 bpm at screening.
15. Has multiple endocrine neoplasia syndrome type 2.
16. Plan for blood donations during the study and within 30 days following completion of or early discontinuation from the trial.
17. Planned bariatric surgery or planned major surgeries during the study time period.
18. Has personal or family history of MEN 2 syndromes or Medullary Thyroid Cancer.
19. Prior hypersensitivity to tirzepatide component.

20. Has hypertension (by medical history or by screening vital signs) and/or known cardiovascular disease.

    Note: If subject presents at screening with elevated blood pressure and no supporting evidence of hypertension; subject may wait approximately 1 hour to have blood pressure rechecked; if readings are still elevated, subject may return to the site approximately 24 hours later to have blood pressure rechecked.

21. Is taking concomitant oral drugs that are dependent on threshold concentrations for efficacy (e.g., antibiotics) since bremelanotide slows gastric emptying and thus has the potential to reduce the rate and extent of absorption of concomitantly administered oral medications
22. Has a diagnosis of type 2 diabetes
23. Has Clinically significant ECG abnormalities on ECG at Screening

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
No Intervention: Placebo
Active Comparator: tirzepatide and bremelanotide Combination Therapy	Drug: bremelanotide; bremelanotide (BMT) sterile aqueous solution for subcutaneous injection, provided as autoinjectors containing 0.3 mL volume; Drug: tirzepatide; tirzepatide (GLP-1/GIP) will be provided in its commercial form for SC injection.
Placebo Comparator: tirzepatide Monotherapy; N=1	Drug: tirzepatide; tirzepatide (GLP-1/GIP) will be provided in its commercial form for SC injection.
Placebo Comparator: bremelanotide Monotherapy	Drug: bremelanotide; bremelanotide (BMT) sterile aqueous solution for subcutaneous injection, provided as autoinjectors containing 0.3 mL volume

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in body weight between treatment arms	Percent change in patient weight from baseline (Visit 2/Day 1) to Visit 10 (Day 57) for the BMT/tirzepatide combination group compared to placebo	Change from the baseline (Visit 2/Day 1) to Visit 10 (Day 57)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analog Scale (VAS) appetite suppression subscales	Change in each of the appetite suppression subscales (hunger, fullness, satiety, prospective food consumption) between treatment arms at Visit 10 (Day 57) Min Value (Satiety, Fullness): 0; Max Value (Satiety, Fullness): 100; Min Value (Hunger, PFC): 100 Max Value (Hunger, PFC): 0. Minimum values indicate a worst score (very hungry). Maximum values indicate a better score (not hungry).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Neck and Waist measurements with a Measuring Tape (Inches)	For men, the circumference of the neck is measured by placing a measuring tape directly on the skin just below the larynx and extending horizontally all the way around the neck. For the abdominal measurement, the tape measure is placed around the belly and over the belly button and extended horizontally all the way around. In addition to neck and waist, testing body fat for women also requires measuring the hips. The neck measurement for women is taken the same way as for men. The method for measuring a woman's waist differs from the method for men. It is measured at the natural waist, which is generally located halfway between the belly button and the sternum. The tape measure needs to be horizontal all the way around and the measurement is taken on the exhale. The hip measurement is taken around the hips, passing over the fullest part of the buttocks, and rounded down to the nearest half inch.	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Evaluating differences in lean muscle mass via Bioimpedance Scale	Change in lean muscle mass through a lean mass assessment conducted with a Bioimpedance Scale between treatment arms at Visit 10 (Day 57).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Glucose levels assessed via blood draw	Changes in Glucose levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Calcium levels assessed via blood draw	Changes in Calcium levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Total Protein levels assessed via blood draw	Changes in Total Protein levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Bilirubin levels assessed via blood draw	Changes in Bilirubin levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in BUN (blood urea nitrogen) levels assessed via blood draw	Changes in BUN (blood urea nitrogen) levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Creatinine levels assessed via blood draw	Changes in Creatinine levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Albumin levels assessed via blood draw	Changes in Albumin levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Sodium levels assessed via blood draw	Changes in Sodium levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Potassium levels assessed via blood draw	Changes in Potassium levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Bicarbonate levels assessed via blood draw	Changes in Bicarbonate levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Chloride levels assessed via blood draw	Changes in Chloride levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Alkaline phosphatase (ALP) levels assessed via blood draw	Changes in Alkaline phosphatase (ALP) levels between treatment arms at Visit 10 (Day 57) assessed via blood draw.	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Alkaline transaminase (ALT) levels assessed via blood draw	Changes in Alkaline transaminase (ALT) levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Aspartate aminotransferase (AST) levels assessed via blood draw	Changes in Aspartate aminotransferase (AST) levels between treatment arms at Visit 10 (Day 57) assessed via blood draw	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Total Cholesterol Levels assessed through blood draw.	Changes in Total Cholesterol Levels assessed through blood draw between treatment arms at Visit 10 (Day 57).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in LDL ("bad") Cholesterol Levels assessed through blood draw.	Changes in LDL ("bad") Cholesterol Levels assessed through blood draw between treatment arms at Visit 10 (Day 57).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in HDL ("good") Cholesterol Levels assessed through blood draw.	Changes in HDL ("good") Cholesterol Levels assessed through blood draw between treatment arms at Visit 10 (Day 57).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Changes in Triglyceride Levels assessed through blood draw.	Changes in Triglyceride Levels assessed through blood draw between treatment arms at Visit 10 (Day 57).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Overall Appetite Suppression Score (OASS) as measured by Visual Analog Scale (VAS)	1. Change in overall appetite suppression as measured by visual analog scale (VAS) between treatment arms at Visit 10 (Day 57) Min Value (OASS): 0; Max Value (OASS): 100. Lower values indicate a worse score (very hungry). Higher values indicate a better score (not hungry).	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in International Index of Erectile Function (IIEF)domain score	Change in the IIEF domain score between treatment arms at Visit 10 (Day 57). Lower value indicates worse erectile function. Higher value indicates better erectile function. Erectile Function: Min- 1 Max- 30 Orgasmic Function: Min- 0 Max- 10 Sexual Desire: Min- 2 Max- 10 Intercourse Satisfaction: Min- 0 Max- 15 Overall Satisfaction: Min- 2 Max- 10	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in the Elements of Desire Questionnaire (EDQ) score	Change in the Elements of Desire Questionnaire (EDQ) score between treatment arms at Visit 10 (Day 57). Min Value: 1; Max Value 5. Lower value indicates worse sexual desire. Higher value indicates better sexual desire.	Change from the Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) in body weight (lbs.) between treatment arms	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Overall Appetite Suppression	This exploratory endpoint is the change from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) in overall appetite suppression, as quantified by the Visual Analog Scale (VAS), between treatment arms. The Hunger and Satiety Visual Analogue Scales (VAS) yields a composite score ranging from 0 to 100, where 0 represents extreme hunger and 100 represents complete satiety. A higher VAS composite score indicates greater appetite suppression efficacy of the treatment.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Appetite Suppression Subscales	This exploratory endpoint assesses the change from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) in individual appetite suppression subscales (hunger, fullness, satiety, and prospective food consumption) between treatment arms. The Hunger and Satiety Visual Analogue Scales (VAS) comprise four distinct subscales, each quantifying specific aspects of appetite suppression: hunger, fullness, satiety, and prospective food consumption. These subscales permit independent assessment.; The hunger subscale, ranging from 0 to 100, quantifies subjective hunger, where 0 indicates minimal hunger and 100 maximal hunger. A score of 0 denotes optimal efficacy.; The fullness subscale, ranging from 0 to 100, quantifies subjective fullness, where 0 signifies absence of fullness and 100 complete fullness. A score of 100 denotes optimal efficacy.; The satiety subscale, ranging from 0 to 100, quantifies subjective satiety, where 0 signifies complete emptiness and 100 comp	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Percent Body Fat	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) in percent body fat between treatment arms	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in BMI	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) in BMI between treatment arms	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Skeletal Muscle Mass	This exploratory endpoint evaluates the change in skeletal muscle mass from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) between treatment arms. Skeletal muscle mass is quantified utilizing Bioelectrical Impedance Analysis (BIA) as the measurement modality. It is acknowledged that the observed range of skeletal muscle mass values is subject to inter-individual variability, influenced by factors including, but not limited to, age, gender, hydration status, recent dietary intake, and body temperature. Skeletal muscle mass assessment will be conducted in conjunction with the analysis of percent body fat and visceral fat level to provide a comprehensive evaluation of lean tissue composition.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Visceral Fat Level	This exploratory endpoint evaluates the change in visceral fat level from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) between treatment arms. Visceral fat is quantified utilizing Bioelectrical Impedance Analysis (BIA) as the measurement modality. It is acknowledged that the observed range of visceral fat values is subject to inter-individual variability, influenced by factors including, but not limited to, age, gender, hydration status, recent dietary intake, and body temperature. A visceral fat assessment will be conducted in conjunction with the analysis of percent body fat and skeletal muscle mass to provide a comprehensive evaluation of lean tissue composition.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Number of participants with abnormal laboratory tests results	This exploratory endpoint evaluates the incidence of participants exhibiting clinically significant changes in laboratory test results from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57), specifically focusing on deviations from reference ranges within the comprehensive metabolic panel (CMP) and lipid panel, between treatment arms.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in Neck and Waist Measurements	This exploratory endpoint evaluates the change in neck and waist circumferences from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) between treatment arms. Circumferential measurements are obtained utilizing a calibrated tape measure with an imperial scale (inches). Neck circumference is determined by measuring the horizontal circumference at the level of the larynx. Waist circumference is assessed at the umbilicus in male participants, and at the midpoint between the inferior border of the sternum and the umbilicus in female participants. In female participants, hip circumference is additionally measured at the level of maximum gluteal protrusion.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in IIEF Domain Score	This exploratory endpoint evaluates the change in the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) between treatment arms. The IIEF questionnaire, utilized for this assessment, yields an EF domain score ranging from 6 to 30, with higher scores indicative of improved erectile function.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)
Change in EDQ Score	This exploratory endpoint evaluates the change in the Elements of Desire Questionnaire (EDQ) total score from Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57) between treatment arms. The Elements of Desire Questionnaire (EDQ) is the instrument employed for this assessment. The total score is derived from the mean of the nine EDQ items, each rated on a scale of 1 to 5, where 5 represents the maximum level of desire and satisfaction.	Change from the Visit 2 baseline and Treatment Period 2 baseline (Day 29) to Visit 10 (Day 57)

Collaborators and Investigators

• Sponsor: Palatin Technologies, Inc
• Investigators: Study Director: Robert Jordan, Palatin

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2024
• Primary Completion (Actual): February 5, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; BMI; Tirzepatide; Bremelanotide
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: BMT-801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No