ObesityPhase 1NCT01867437
Effects of RM-493 on Energy Expenditure in Obese Individuals
A Phase 1 study testing RM-493 in people with Obesity and Morbid Obesity, run by Rhythm Pharmaceuticals, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Morbid Obesity
- What is being tested?
- RM-493
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Mar 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female subjects aged 18 to 50 years at screening who meet the following inclusion and exclusion criteria will be eligible for enrollment:
- 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.
Who cannot join
- 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%
Show all 23Show fewer
- 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)
- Any history of cancer, including personal history or close family history (parents or siblings) of melanoma; and/or personal history of multiple atypical nevi, nevoid basal cell carcinoma syndrome, or a personal history of non-melanoma skin cancer.
- Bariatric surgery
- History of recent surgery (within 60 days of screening)
- Current or recent (within last month) infection or viral illness
- Prescription drug use including topical steroids and inhalers, and non-prescription medicines with sympathomimetic actions (eg decongestants) if not stopped 1 week prior to and throughout the admission.
- Weight loss or gain of greater than 3% of body weight in last 3 months
- Inflexible dietary restrictions
- Actively training athletes (collegiate or professional level)
- Cigarette smoking (must be completely nonsmoking for at least 2 months)
- Dependence on caffeine, alcohol or drugs; unable or unwilling to abstain completely from caffeine and related substances for 72 hours prior to study and throughout the study
- Claustrophobia or other psychiatric conditions that would preclude participation in all aspects of the study
- Unable or unwilling to wear an insulin pump for the 6 days of treatment during the study (to deliver test drug and placebo)
- Participation in an investigational clinical study within the 30 days prior to dosing in the present study
- Any other reason, which in the opinion of the Investigator, would confound proper interpretation of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, 2-Period Crossover Study to Evaluate the Effect of RM-493 on Energy Expenditure in Obese Subjects
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.
Read more
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.
Read the detailed description
Obesity is a chronic relapsing health problem and a strong risk factor for type 2 diabetes, hypertension, heart disease and stroke. Life expectancy is shorter in obese individuals who often suffer from costly related co-morbidities such as certain cancers, liver disease, osteoarthritis, sleep apnea and depression. Weight loss improves the co-morbidities. Diet and exercise are effective in the short term, but are rarely effective over a span of years. New therapies are needed especially for patients with obesity. The melanocortin system, and specifically, melanocortin 4 receptor (MC4R) is involved in the regulation of energy homeostasis and body weight. This role is validated in human genetic mutations, and in animal models of obesity, stimulation of MC4R reduces food intake and increases metabolic rate, causing a reduction in body weight.
RM-493 is a potent, selective peptide agonist for the MC4R that suppressed food intake and reduced body weight in preclinical studies. RM-493 has been studied in single dose and multiple ascending dose clinical studies in obese volunteers. This study is a randomized, double-blind, placebo-controlled, multiple-dose, 2-period, crossover study to assess the effects of RM-493 on resting energy expenditure measured in a room calorimeter. Twelve obese but otherwise healthy adult subjects between the ages of 18 and 50 inclusive, will be enrolled and randomized to one of 2 treatment sequences (RM-493 then placebo; or placebo then RM-493) over an 8-day study interval. Components of 24-hour energy expenditure, exercise induced energy expenditure, spontaneous physical activity, respiratory quotient, safety and pharmacokinetic data will be collected.
- Conditions
- Obesity, Morbid Obesity
- Being tested
- Placebo, RM-493
- Keywords
- 24 Hour Energy Expenditure, Resting Energy Expenditure, Obesity, Healthy Volunteers
- Medical subject headings
- Obesity, Obesity, Morbid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Sterile solution (vehicle) for subcutaneous infusion
RM-493Drug
Sterile solution (2mg/ml) for subcutaneous infusion
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: RM-493 |
| Placebo | Placebo comparator | Double blind placebo will be administered via subcutaneous infusion for 3 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects
Measured: 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
Measured: day 4 and day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study startMay 2013
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Monica C Skarulis, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01867437
- Sponsor's protocol ID
- 130136
- Other IDs
- 13-DK-0136
- Status last verified
- Apr 2017
- First submitted
- 22 May 2013
- Last updated
- 20 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab. 2004 Jun;89(6):2522-5. doi: 10.1210/jc.2004-0288.
PubMed 15181019Withrow 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.
PubMed 20122135Nguyen 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.
PubMed 20202574Chen 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.
PubMed 25675384
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, 2-Period Crossover Study to Evaluate the Effect of RM-493 on Energy Expenditure in Obese Subjects
- ClinicalTrials.gov ID
- NCT01867437
- Acronym / sponsor ID
- 130136
- Conditions
- Obesity, Morbid Obesity
- Keywords
- 24 Hour Energy Expenditure, Resting Energy Expenditure, Obesity, Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2013 (actual)
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 4 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Obesity is a chronic relapsing health problem and a strong risk factor for type 2 diabetes, hypertension, heart disease and stroke. Life expectancy is shorter in obese individuals who often suffer from costly related co-morbidities such as certain cancers, liver disease, osteoarthritis, sleep apnea and depression. Weight loss improves the co-morbidities. Diet and exercise are effective in the short term, but are rarely effective over a span of years. New therapies are needed especially for patients with obesity. The melanocortin system, and specifically, melanocortin 4 receptor (MC4R) is involved in the regulation of energy homeostasis and body weight. This role is validated in human genetic mutations, and in animal models of obesity, stimulation of MC4R reduces food intake and increases metabolic rate, causing a reduction in body weight.
RM-493 is a potent, selective peptide agonist for the MC4R that suppressed food intake and reduced body weight in preclinical studies. RM-493 has been studied in single dose and multiple ascending dose clinical studies in obese volunteers. This study is a randomized, double-blind, placebo-controlled, multiple-dose, 2-period, crossover study to assess the effects of RM-493 on resting energy expenditure measured in a room calorimeter. Twelve obese but otherwise healthy adult subjects between the ages of 18 and 50 inclusive, will be enrolled and randomized to one of 2 treatment sequences (RM-493 then placebo; or placebo then RM-493) over an 8-day study interval. Components of 24-hour energy expenditure, exercise induced energy expenditure, spontaneous physical activity, respiratory quotient, safety and pharmacokinetic data will be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RM-493 | Active comparator | Drug: RM-493Double blind RM-493 will be administered at a dose of 1 mg/24 hrs via subcutaneous infusion for 3 days |
| Placebo | Placebo comparator | Drug: PlaceboDouble blind placebo will be administered via subcutaneous infusion for 3 days |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male and female subjects aged 18 to 50 years at screening who meet the following inclusion and exclusion criteria will be eligible for enrollment:
- 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).
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboSterile solution (vehicle) for subcutaneous infusion | Drug | Placebo |
| RM-493Sterile solution (2mg/ml) for subcutaneous infusion | Drug | RM-493 |
Primary outcome
Resting energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects
Time frame: day 4 and day 7
1 secondary outcome
Total energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects
Time frame: day 4 and day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2017.
- Background: PubMed 15181019Stein CJ, Colditz GA. The epidemic of obesity. J Clin Endocrinol Metab. 2004 Jun;89(6):2522-5. doi: 10.1210/jc.2004-0288.
- Background: PubMed 20122135Withrow 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.
- Background: PubMed 20202574Nguyen 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.
- Derived from this study: PubMed 25675384Chen 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monica C Skarulis, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RM-493 in people with Obesity and Morbid Obesity, run by Rhythm Pharmaceuticals, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects (time frame: day 4 and day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01867437, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2017.