Obese, Overweight
Conditions
Keywords
Heterozygous, MC4R deficiency, associated
Brief summary
The purpose of this study is to evaluate the multiple dose safety and tolerability of RM-493 (setmelanotide) as well as pharmacokinetic (PK) and pharmacodynamic (PD; weight loss) profile, in healthy obese patients for 2 to 4 weeks. In addition, one panel of patients with a specific genetic deficiency in the hypothalamic leptin- proopiomelanocortin (POMC) - melanocortin-4 receptor (MC4R) pathway, those with heterozygous partial or full loss of function (LOF) of the MC4R gene, will also be studied. The study drug (RM-493 and placebo) will be administered subcutaneously in a blinded fashion by subcutaneous (SC) infusion or injection.
Interventions
DRUGRM-493
DRUGPlacebo
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures. * Healthy obese male and female volunteers aged 18 to 55 years, inclusive. Heterozygous subjects may be 18 to 65 years inclusive. * In good general health, without significant medical history, physical examination findings, or clinical laboratory abnormalities. * Body Mass Index of 30-40 kg/m2, inclusive. Heterozygous subjects may have a broader BMI range; to be eligible heterozygous subjects may have a BMI 27 -55 kg/ m2, inclusive. * Stable body weight during the previous 6 months, based on Investigator judgment. * Blood pressure \<140/90 mmHg at Screening and D-1. Measurement may be repeated within 24 hours, based on Investigator judgment. * Females must not be pregnant and must have a negative serum pregnancy test result at the Screening Visit and Day -1. * Females of childbearing potential must agree to be abstinent or else use any two of the following medically acceptable forms of contraception from the Screening Period through the Final Study Visit: hormonal, condom with spermicidal jelly, diaphragm or cervical cap with spermicidal jelly, or IUD. Hormonal contraception must have started at least 3 months prior to screening. A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception. Subjects must agree to practice the above birth control methods for 30 days from the final visit as a safety precaution. * 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 range), do not require contraception during the study. * Males with female partners of childbearing potential must agree to use two medically acceptable forms of contraception as described above, with one of the two forms being condom with spermicide, from the Screening Period through the Final Study Visit. Males with female partners of childbearing potential who themselves are surgically sterile (status post vasectomy) must agree to use condoms with spermicide over the same period of time. Male subjects must agree to practice the above birth control methods for 30 days from the final visit as a safety precaution.
Exclusion criteria
* Fasting blood glucose \>126 mg/dL at screening. Heterozygous subjects will be excluded for a fasting blood glucose \>140 mg/dL. * Resting heart rate \<45 bpm or \>90 bpm at screening. * Abnormal thyroid stimulating hormone (TSH) or thyroxine (T4) levels on screening. * Elevated ALT or serum creatinine on screening or any clinically significant abnormalities on screening laboratory tests as determined by the Investigator. * History of medically treated diabetes or of treated or medically diagnosed hypertension. Heterozygous subjects who have diagnosed hypertension and are well controlled on treatment (Refer to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of adverse events. | Day 1 through Day 14 or Day 28 (depending on Cohort) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) Profile | Day 1 through Day 14 or Day 28 (depending on Cohort) | Frequent PK (trough) sampling throughout the study, including 24-hour inpatient PK profiles at the beginning and end of the study. |
| Assessment of weight loss based on weight measurements | Day 1 through Day 14 or Day 28 (depending on Cohort) | — |
| Assessment of blood pressure using Ambulatory blood pressure monitors. | Day 1 through Day 14 or Day 28 (depending on Cohort) | — |
Outcome results
None listed