Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RM-493 Administered to Healthy, Obese, Non-diabetic Volunteers

NCT02431442 | Completed Phase 1

• 1 other identifier: RM-493-002
• Study Type: interventional
• Target: 57
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Overweight; Obese

Keywords

Heterozygous; MC4R deficiency; associated

Outcome Measures

Primary Outcomes (1)

• Number of adverse events.

  Day 1 through Day 14 or Day 28 (depending on Cohort)

Secondary Outcomes (3)

• Pharmacokinetics (PK) Profile

  Day 1 through Day 14 or Day 28 (depending on Cohort)

• 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)

Study Arms (12)

Cohort 1: RM-493 SC Infusion 14 Days

ACTIVE COMPARATOR

Double-blind RM-493 will be administered at a dose of 0.01 mg/kg/24 hours via subcutaneous continuous infusion for 14 days (1 panel, all male subjects)

Drug: RM-493

Cohort 2: RM-493 SC Infusion 28 Days

ACTIVE COMPARATOR

Double-blind RM-493 will be administered at a dose of 0.01 mg/kg/24 hours via subcutaneous continuous infusion for 28 days (1 panel)

Drug: RM-493

Cohort 3: RM-493 SC Infusion 28 Days

ACTIVE COMPARATOR

Double-blind RM-493 will be administered at a dose of 0.01 mg/kg/24 hours via subcutaneous continuous infusion for 28 days (1 panel)

Drug: RM-493

Cohort 4: RM-493 SC Infusion 28 Days

ACTIVE COMPARATOR

Double-blind RM-493 will be administered at a dose of 0.015 mg/kg/24 hours via subcutaneous continuous infusion for 28 days (1 panel)

Drug: RM-493

Cohort 5: RM-493 SC Injection 14 days

ACTIVE COMPARATOR

Double-blind RM-493 will be administered at a dose of 0.0075 mg/kg every 12 hours via a subcutaneous injection for 14 days (1 panel)

Drug: RM-493

Cohort 6: RM-493 SC Infusion 28 Days

ACTIVE COMPARATOR

Double-blind RM-493 will be administered at a dose of 0.01 mg/kg/24 hours via subcutaneous continuous infusion for 28 days (1 panel, heterozygous MC4R subjects)

Drug: RM-493

Cohort 1: Placebo SC Infusion 14 Days

PLACEBO COMPARATOR

Double-blind Placebo will be administered via subcutaneous continuous infusion for 14 days (1 panel, all male subject)

Drug: Placebo

Cohort 2: Placebo SC Infusion 28 Days

PLACEBO COMPARATOR

Double-blind Placebo will be via subcutaneous continuous infusion for 14 days (1 panel)

Drug: Placebo

Cohort 3: Placebo SC Infusion 28 Days

PLACEBO COMPARATOR

Double-blind Placebo will be administered via subcutaneous continuous infusion for 28 days (1 panel)

Drug: Placebo

Cohort 4: Placebo SC Infusion 28 Days

PLACEBO COMPARATOR

Double-blind Placebo will be administered via subcutaneous continuous infusion for 28 days (1 panel)

Drug: Placebo

Cohort 5: Placebo SC Injection 14 days

PLACEBO COMPARATOR

Double-blind Placebo will be administered via a subcutaneous injection every 12 hours for 14 days (1 panel)

Drug: Placebo

Cohort 6: Placebo SC Infusion 28 Days

PLACEBO COMPARATOR

Double-blind Placebo will be administered via subcutaneous continuous infusion for 28 days (1 panel, heterozygous MC4R subjects)

Drug: Placebo

Interventions

RM-493 DRUG

Also known as: setmelanotide

Cohort 1: RM-493 SC Infusion 14 Days; Cohort 2: RM-493 SC Infusion 28 Days; Cohort 3: RM-493 SC Infusion 28 Days; Cohort 4: RM-493 SC Infusion 28 Days; Cohort 5: RM-493 SC Injection 14 days; Cohort 6: RM-493 SC Infusion 28 Days

Placebo DRUG

Cohort 1: Placebo SC Infusion 14 Days; Cohort 2: Placebo SC Infusion 28 Days; Cohort 3: Placebo SC Infusion 28 Days; Cohort 4: Placebo SC Infusion 28 Days; Cohort 5: Placebo SC Injection 14 days; Cohort 6: Placebo SC Infusion 28 Days

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Presence of a skin lesion suspicious for malignancy, unless excised prior to Day 1.
• History of malignancy except for treated cervical carcinoma in situ in the past 5 years.
• Active or history of any clinically significant medical condition including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic, psychiatric or hematological disease, based on Investigator judgment.
• Acute illness or history of illness, which in the opinion of the Investigator, could pose a threat or harm to the subject or obscure interpretation of laboratory test results or interpretation of study data.
• Positive hepatitis B surface antigen, positive hepatitis C antibody or positive HIV test at screening or a history of positive testing (e.g. liver biopsy, serology) suggesting acute or chronic hepatitis.
• Abnormal 12-lead electrocardiogram (ECG) at screening or pre-dose (Day -1 or Day 1), except minor deviations deemed to be of no clinical significance by the Investigator.
• Received any experimental drugs or devices within 30 days or 5 half lives, whichever is longer, prior to dosing.
• Ongoing participation in a prior clinical study at the time of screening.
• Blood donation within 60 days prior to screening or intent to donate within 60 days after Final Study Visit.
• Hospitalization for major surgery including but not limited to abdominal, thoracic, or cardiovascular surgery within the past 3 months prior to screening, or for a clinically significant non-surgical illness, based on Investigator judgment, within the past 3 months.
• Planned elective surgery within 30 days of the Final Study Visit.

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Overweight; Obesity

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Elizabeth Stoner, MD

  Rhythm Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: May 1, 2015
• Study Start: January 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: May 1, 2015

Record last verified: 2015-04