Effects of RM-493 on Energy Expenditure in Obese Individuals

NCT01867437 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13013613-DK-0136
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- RM-493 is a drug that stimulates parts of the brain that control eating and metabolism. It has helped to reduce body weight and improve insulin sensitivity in lab tests. However, it is not fully known whether RM-493 causes weight loss by just decreasing appetite or by increasing metabolism or both. Researchers want to see how RM-493 affects metabolism and hormones that affect the metabolic rate. They also want to see how RM-493 affects appetite by assessing feelings of hunger and fullness. They will study this drug in people who are obese but are otherwise in good health. Objectives: \- To see how RM-493 affects metabolic rate and appetite in obese but otherwise healthy individuals. Eligibility: \- Individuals between 18 and 50 years old who are obese (body mass index between 30 and 40 kg/m2) but are otherwise healthy. Design:

• The study consists of three phases. The first phase is the screening visit. The second phase is an 8-day inpatient stay. The final phase is a follow-up phone call one week after the end of the second phase.
• Participants will be divided into two groups. One group will receive the study drug first, followed by a placebo. The other group will receive the placebo followed by the study drug. The study drug and placebo will be given under the skin for 3 days each by a small device (OmniPod) that normally is used to give insulin to people with diabetes.
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. They will also meet with a dietitian. The OmniPod device will be demonstrated before use.
• Participants will have the following procedures during their 8-day inpatient stay:
• Daily exercise routine (walking on treadmill) after setting a comfortable pace (miles per hour) during an exercise test
• Wear physical activity monitors
• Body composition study to measure amounts of fat and muscle
• Calorie controlled study diet
• Study drug/placebo dose through the OmniPod (Days 2 through 4 and 5 through 7)
• Metabolic rate studies using a cart or the metabolic chamber
• Daily blood samples
• Urine collection for 24 hours
• Questions about weight history and appetite
• About a week after the inpatient stay, participants will have a followup phone call to ask about any side effects from the study.

Conditions

Obesity; Morbid Obesity

Keywords

24 Hour Energy Expenditure; Resting Energy Expenditure; Obesity; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Resting energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects

  day 4 and day 7

Secondary Outcomes (1)

• Total energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects

  day 4 and day 7

Study Arms (2)

RM-493

ACTIVE COMPARATOR

Double blind RM-493 will be administered at a dose of 1 mg/24 hrs via subcutaneous infusion for 3 days

Drug: RM-493

Placebo

PLACEBO COMPARATOR

Double blind placebo will be administered via subcutaneous infusion for 3 days

Drug: Placebo

Interventions

Placebo DRUG

Sterile solution (vehicle) for subcutaneous infusion

Placebo

RM-493 DRUG

Sterile solution (2mg/ml) for subcutaneous infusion

RM-493

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Able to provide written informed consent prior to any study procedures, and be willing and able to comply with study procedures
• Body mass index of 30-40 kg/m(2)
• Subjects who are medically healthy with normal or clinically insignificant screening results (laboratory profiles, medical histories, electrocardiograms and physical examination)
• Female subjects must have negative serum or urine pregnancy tests and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control or abstinence must be used/ practiced throughout the study. Female subjects unable to bear children must have this documented in the case report form (CRF) (i.e., tubal ligation, hysterectomy, or post-menopausal \[defined as a minimum of one year since the last menstrual period\]). Post-menopausal status will be confirmed by follicle stimulating hormone (FSH).
• Female subjects must have a negative serum pregnancy test prior to administering the OmniPod in both Period 1 and Period 2 to continue in 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 follow up phone call after completion of study treatment. 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.
• Pregnant or lactating women
• Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator
• Abnormal 12-lead electrocardiogram (ECG) except minor deviations deemed to be of no clinical significance by the Investigator
• ALT or AST \> 1.5 times the upper limit of normal (ULN) during screening
• Treated or untreated hypertension or blood pressure 140/90
• Treated or untreated diabetes diagnosed as fasting plasma glucose 126 or a HbA1c 6.5%
• TSH outside of the normal range
• Active or history of any significant medical condition such as and including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
• Clinical symptoms of or treatment for sleep apnea (severe snoring, excessive daytime somnolence)

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab. 2004 Jun;89(6):2522-5. doi: 10.1210/jc.2004-0288.

  PMID: 15181019 BACKGROUND

• Withrow D, Alter DA. The economic burden of obesity worldwide: a systematic review of the direct costs of obesity. Obes Rev. 2011 Feb;12(2):131-41. doi: 10.1111/j.1467-789X.2009.00712.x.

  PMID: 20122135 BACKGROUND

• Nguyen DM, El-Serag HB. The epidemiology of obesity. Gastroenterol Clin North Am. 2010 Mar;39(1):1-7. doi: 10.1016/j.gtc.2009.12.014.

  PMID: 20202574 BACKGROUND

• Chen KY, Muniyappa R, Abel BS, Mullins KP, Staker P, Brychta RJ, Zhao X, Ring M, Psota TL, Cone RD, Panaro BL, Gottesdiener KM, Van der Ploeg LH, Reitman ML, Skarulis MC. RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals. J Clin Endocrinol Metab. 2015 Apr;100(4):1639-45. doi: 10.1210/jc.2014-4024. Epub 2015 Feb 12.

  PMID: 25675384 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Obesity; Obesity, Morbid

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

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

Study Officials

• Monica C Skarulis, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 22, 2013
• First Posted: June 4, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 20, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)