A Staged, Phase 1b/Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety and Efficacy of RM-493, a Melanocortin 4 Receptor (MC4R) Agonist in Obese Patients Using a Once or Twice Daily Sub-Cutaneous Injection Formulation
Overview
- Phase
- Phase 1
- Intervention
- Setmelanotide
- Conditions
- Overweight and Obesity
- Sponsor
- Rhythm Pharmaceuticals, Inc.
- Enrollment
- 99
- Primary Endpoint
- Body Weight - Stage C
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the effects of a new daily subcutaneous (SC) injectable formulation of setmelanotide (RM-493) in healthy participants with obesity on mean percent body weight loss and other weight loss parameters, as well as pharmacokinetic (PK) profile. The study is designed to evaluate the efficacy and tolerability of setmelanotide administered once or twice daily. The study drug (setmelanotide and placebo) will be administered in a blinded fashion.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Be between the ages of 18 and 65 years, inclusive.
- •Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures.
- •In good general health, without significant medical history, physical examination findings, or clinical laboratory abnormalities.
- •Body Mass Index: 30 to 40 Kg/m
- •Stable body weight by participant report (+/- 5 Kg) during previous 6 months.
- •Blood pressure (\<140/90 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications to achieve control and that are intended to remain on a stable dose during the protocol.
- •Willingness (during screening) and demonstrated ability (as witnessed in the clinic prior to randomization) to self-administer study medication subcutaneously via a once or twice daily SC injection using a small insulin syringe.
- •Willing to maintain a healthy diet and exercise regime throughout study as recommended by counseling at study start.
- •Female participants must have negative serum pregnancy test and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method (i.e., sponge), or a double-barrier method of birth control (i.e., condom with spermicide) or abstinence must be used/ practiced throughout the study and for 90 days following the study.
- •Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months (and confirmed with a screening FSH level in the post-menopausal lab range), do not require contraception during the study.
Exclusion Criteria
- •Fasting blood glucose \> than 140 mg/dL.
- •TSH level outside the normal range.
- •Creatinine \> 1.5 times the upper limit of normal.
- •Liver function tests \> 2 times the upper limit of normal.
- •Active or history of any significant medical condition including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
- •Patients with a history of the following:
- •Uncontrolled hypertension;
- •Diabetes requiring medical treatment;
- •Major depressive disorder within the last 2 years;
- •Any lifetime history of a suicide attempt;
Arms & Interventions
Setmelanotide Once Daily
Once daily in the morning, equivalent placebo in evening.
Intervention: Setmelanotide
Setmelanotide Once Daily
Once daily in the morning, equivalent placebo in evening.
Intervention: Placebo
Setmelanotide Split Dose
Split dose, one half in the morning and one half in the evening.
Intervention: Setmelanotide
Placebo
Placebo in the morning, placebo in the evening.
Intervention: Placebo
Outcomes
Primary Outcomes
Body Weight - Stage C
Time Frame: Baseline
Body Weight - Stage A
Time Frame: Baseline
Body Weight - Stage B
Time Frame: Baseline
Percent Change From Baseline in Body Weight at Week 12 - Stage A
Time Frame: Baseline, Week 12
Percent Change From Baseline in Body Weight at Week 12 - Stage B
Time Frame: Baseline, Week 12
Percent Change From Baseline in Body Weight at Week 12 - Stage C
Time Frame: Baseline, Week 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - Stage A
Time Frame: From first dose up to Day 114
An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs that occurred after the start of study drug administration were considered TEAEs.
Number of Participants With TEAEs - Stage C
Time Frame: From first dose up to Day 114
An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs that occurred after the start of study drug administration were considered TEAEs.
Number of Participants With TEAEs - Stage B
Time Frame: From first dose up to Day 114
An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs that occurred after the start of study drug administration were considered TEAEs.
Secondary Outcomes
- Mean Setmelanotide Concentrations During a 24-Hour Steady State Interval on Day 8 - Stage A(Predose (0 hours) and at 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24 hours after dosing on Day 8)
- Mean Setmelanotide Concentrations During a 24-Hour Steady State Interval on Day 8 - Stage C(Predose (0 hours) and at 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours after dosing on Day 8)
- Change From Baseline in Ambulatory Blood Pressure Monitoring (ABPM) Parameters During 24-Hour Interval Between Days 8 and 15 - Stage A(Baseline and for one 24-hour interval between Days 8 or 15)
- Change From Baseline in ABPM Parameters During 24-Hour Interval Between Days 8 and 15 - Stage C(Baseline and for one 24-hour interval between Days 8 or 15)
- Change From Baseline in Heart Rate Using ABPM During 24-Hour Interval Between Days 8 and 15 - Stage C(Baseline and for one 24-hour interval between Days 8 and 15)
- Change From Baseline in Heart Rate Using ABPM During 24-Hour Interval Between Days 8 and 15 - Stage A(Baseline and for one 24-hour interval between Days 8 and 15)