OverweightPhase 1NCT02431442

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

A Phase 1 study testing RM-493 in people with Overweight and Obese, run by Rhythm Pharmaceuticals, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Overweight, Obese
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: 57 participants
Where: No sites listed yet
Study dates: Jan 2012to Jan 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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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 Exclusion Criteria 20 below), are eligible. .
Presence of a skin lesion suspicious for malignancy, unless excised prior to Day 1.

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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.
Poor venous access or inability to tolerate venipuncture.
History of significant drug hypersensitivity or anaphylaxis.
History of hypersensitivity to proteins (e.g., allergy shots).
Use of prescription medications on a regular basis. The last use of any prescription medication must have been greater than 5 half-lives for the specific medication or at least 14 days prior to admission (Day -1), whichever is longer. Hormonal contraception is allowed for female subjects.
Heterozygous cohorts: Use of prescription medications on a regular basis is not allowed with the following exceptions:
Antihypertensives (<3 medications on a stable dose for ≥ 30 days);
Statins (dose must be ≤ half the maximum dose; must be on a stable dose ≥3 months);
Fibrates (must be on stable dose for ≥3 months);
Niacin (must be on stable dose for ≥3 months);
Thyroxin (stable dose for ≥ 30 days); The last use of any other prescription medication will need follow the criteria for all other cohorts, as outlined above.
Use of prescription medications not listed above may be allowed at the discretion of the Investigator upon consultation with Rhythm.
Use of a non-prescription drug and herbal substances during the study (through the Final Study Visit). The last dose of any non-prescription drug must have been taken greater than 5 half-lives for that drug before receiving study drug.
Inability to attend all study visits or to comply with protocol requirements including fasting and restrictions on alcohol, caffeine, nicotine and concomitant medication intake.
A significant history of drug/solvent abuse within 5 years of screening or a positive test for drugs of abuse test at screening or on Day -1.
Positive alcohol (breath test) or nicotine screen at Screening Visit or Day 1 (positive nicotine screen does not apply to heterozygous cohort).
History of alcohol abuse (defined as average intake of three or more units of alcohol per day) within 5 years of the Screening Visit.
History of tobacco or tobacco product use unless abstinent for at least one year prior to the Screening Visit. This criterion does not apply to heterozygous subjects.
Previously randomized and dosed in this study. This criterion does not apply to heterozygous subjects.
Any other reason, which in the opinion of the Investigator would confound proper evaluation of the study.

About this study

Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RM 493 Administered to Healthy Obese Non-diabetic Volunteers

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
Being tested: RM-493, Placebo
Keywords: Heterozygous, MC4R deficiency, associated
Medical subject headings: Overweight, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RM-493Drug
Also called setmelanotide
PlaceboDrug

Study groups in NCT02431442
Study group	Role	What they receive
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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of adverse events.
Measured: Day 1 through Day 14 or Day 28 (depending on Cohort)

Secondary outcomes (3)

Pharmacokinetics (PK) Profile
Frequent PK (trough) sampling throughout the study, including 24-hour inpatient PK profiles at the beginning and end of the study.
Measured: Day 1 through Day 14 or Day 28 (depending on Cohort)
Assessment of weight loss based on weight measurements
Measured: Day 1 through Day 14 or Day 28 (depending on Cohort)
Assessment of blood pressure using Ambulatory blood pressure monitors.
Measured: Day 1 through Day 14 or Day 28 (depending on Cohort)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2012Jan 2014

First posted1 May 2015 (estimated)
Study startJan 2012
Primary completionJan 2014
Study completionJan 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for OverweightStudies 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: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02431442
Sponsor's protocol ID: RM-493-002
Status last verified: Apr 2015
First submitted: 22 Apr 2015
Last updated: 1 May 2015
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 1 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RM 493 Administered to Healthy Obese Non-diabetic Volunteers
ClinicalTrials.gov ID: NCT02431442
Acronym / sponsor ID: RM-493-002
Conditions: Overweight, Obese
Keywords: Heterozygous, MC4R deficiency, associated
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 57 participants (actual)
Lead sponsor: Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: Jan 2012
Primary completion: Jan 2014 (actual)
Study completion: Jan 2014 (actual)
First posted: 1 May 2015 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 12

Arm	Type	Receives
Cohort 1: RM-493 SC Infusion 14 Days	Active comparator	Drug: RM-493Double-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)
Cohort 2: RM-493 SC Infusion 28 Days	Active comparator	Drug: RM-493Double-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)
Cohort 3: RM-493 SC Infusion 28 Days	Active comparator	Drug: RM-493Double-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)
Cohort 4: RM-493 SC Infusion 28 Days	Active comparator	Drug: RM-493Double-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)
Cohort 5: RM-493 SC Injection 14 days	Active comparator	Drug: RM-493Double-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)
Cohort 6: RM-493 SC Infusion 28 Days	Active comparator	Drug: RM-493Double-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)
Cohort 1: Placebo SC Infusion 14 Days	Placebo comparator	Drug: PlaceboDouble-blind Placebo will be administered via subcutaneous continuous infusion for 14 days (1 panel, all male subject)
Cohort 2: Placebo SC Infusion 28 Days	Placebo comparator	Drug: PlaceboDouble-blind Placebo will be via subcutaneous continuous infusion for 14 days (1 panel)
Cohort 3: Placebo SC Infusion 28 Days	Placebo comparator	Drug: PlaceboDouble-blind Placebo will be administered via subcutaneous continuous infusion for 28 days (1 panel)
Cohort 4: Placebo SC Infusion 28 Days	Placebo comparator	Drug: PlaceboDouble-blind Placebo will be administered via subcutaneous continuous infusion for 28 days (1 panel)
Cohort 5: Placebo SC Injection 14 days	Placebo comparator	Drug: PlaceboDouble-blind Placebo will be administered via a subcutaneous injection every 12 hours for 14 days (1 panel)
Cohort 6: Placebo SC Infusion 28 Days	Placebo comparator	Drug: PlaceboDouble-blind Placebo will be administered via subcutaneous continuous infusion for 28 days (1 panel, heterozygous MC4R subjects)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (35 listed)

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 Exclusion Criteria 20 below), are eligible. .

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
RM-493Also: setmelanotide	Drug	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

Primary outcome

Number of adverse events.
Time frame: Day 1 through Day 14 or Day 28 (depending on Cohort)

3 secondary outcomes

Pharmacokinetics (PK) Profile
Time frame: Day 1 through Day 14 or Day 28 (depending on Cohort)
Assessment of weight loss based on weight measurements
Time frame: Day 1 through Day 14 or Day 28 (depending on Cohort)
Assessment of blood pressure using Ambulatory blood pressure monitors.
Time frame: Day 1 through Day 14 or Day 28 (depending on Cohort)

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 1 May 2015.

Related trials for Overweight

RecruitingObservational study
Endoscopic Sleeve Gastroplasty (ESG) Prospective Trial for Obesity (EGO-Trial)
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Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
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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.

Elizabeth Stoner, MD study director

Rhythm Pharmaceuticals, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RM-493 in people with Overweight and Obese, run by Rhythm Pharmaceuticals, Inc..

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 10 inclusion and 35 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 1 May 2015. Status can change between updates, so confirm with the study contact before making plans.

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?

Number of adverse events. (time frame: Day 1 through Day 14 or Day 28 (depending on Cohort)). 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 NCT02431442.

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 1 May 2015.