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Phase 1b/2a Study to Evaluate Safety and Efficacy of RM-493 in Obese Patients

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ClinicalTrials.gov Identifier: NCT02041195
Recruitment Status : Completed
First Posted : January 20, 2014
Last Update Posted : May 5, 2015
Sponsor:
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.

Brief Summary:
The purpose of this study is to evaluate the effects of a new daily subcutaneous (SC) injectable formulation of RM-493 in healthy obese subjects on mean percent body weight loss and other weight loss parameters, as well as Pharmacokinetic (PK) profile. The study is designed to evaluate the efficacy and tolerability of RM-493 administered once or twice daily. The study drug (RM-493 and placebo) will be administered in a blinded fashion.

Condition or disease Intervention/treatment Phase
Overweight Drug: RM-493 Drug: Placebo Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Staged, Phase 1b/Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety and Efficacy of RM 493, a Melanocortin 4 Receptor (MC4R) Agonist in Obese Patients Using a Once or Twice Daily Sub-Cutaneous Injection Formulation
Study Start Date : January 2014
Actual Primary Completion Date : August 2014
Actual Study Completion Date : December 2014

Arm Intervention/treatment
Active Comparator: RM-493 Once Daily
Once daily in the morning, equivalent PBO in evening.
Drug: RM-493
Drug: Placebo
Active Comparator: RM-493 Split Dose
Split dose, one half in the morning and one half in the evening.
Drug: RM-493
Placebo Comparator: Placebo
Placebo in the morning, placebo in the evening.
Drug: Placebo



Primary Outcome Measures :
  1. Effect on mean percent weight loss [ Time Frame: Baseline to end of treatment (12 weeks) ]
    The effect of RM-493 (once or twice daily) vs. placebo on mean percent body weight loss.

  2. Safety and Tolerability of RM-493 [ Time Frame: Baseline to end of treatment (12 weeks) ]
    Assessment of adverse events and clinical laboratory evaluations.


Secondary Outcome Measures :
  1. Effect on mean body weight loss [ Time Frame: Baseline to end of treatment (12 weeks) ]
    Measurement of effect on mean body weight (BW) loss.

  2. Effect of RM-493 on Pharmacokinetics (PK) [ Time Frame: Baseline to end of treatment (12 weeks) ]
    Frequent PK (trough) sampling throughout each stage of the study, including a 24-hour inpatient PK profile.

  3. Effect of RM-493 on ambulatory blood pressure monitoring (ABPM) in a subset of patients [ Time Frame: Baseline, and over one 24-hr period between Days 8 and 15 ]
    The effect of RM-493 on ambulatory blood pressure monitoring parameters (ABPM).


Other Outcome Measures:
  1. The proportion of patients who achieve a ≥ 5 and 10% decrease in body weight. [ Time Frame: Baseline to end of treatment (12 weeks) ]
    The proportion of patients who achieve a ≥ 5 and 10% decrease in body weight in the active treatment group compared to placebo.

  2. Effect of RM-493 on fasting glucose. [ Time Frame: Baseline to end of treatment (12 weeks) ]
    Measurement of the effect of RM-493 on fasting glucose.

  3. Effect of RM-493 on waist circumference [ Time Frame: Baseline to end of treatment (12 weeks) ]
    Measurement of the effect of RM-493 on waist circumference.

  4. Change in depression/suicidality. [ Time Frame: Screening to end of treatment (12 weeks) ]
    Measurement of the change in the depression/suicidality score as assessed by Patient Health Questionnaire 9 (PHQ-9) and the Columbia Suicidality Severity Rating Scale (C-SSRS).



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be between the age of 18 and 65 inclusive.
  • Able to provide voluntary, written informed consent with comprehension of all aspects of the protocol, prior to any study procedures.
  • In good general health, without significant medical history, physical examination findings, or clinical laboratory abnormalities.
  • Body Mass Index: 30 to 40 Kg/m2.
  • Stable body weight by subject report (+/- 5 Kg) during previous 6 months.
  • Blood pressure (<140/90 mmHg); may include stable dose (≥ 30 days of use) of up to two anti-hypertensive medications to achieve control and that are intended to remain on a stable dose during the protocol. Patients slightly out of range can participate at the discretion of the investigator.
  • Willingness (during screening) and demonstrated ability (as witnessed in the clinic prior to randomization) to self-administer study medication subcutaneously via a once or twice daily SC injection using a small insulin syringe.
  • Willing to maintain a healthy diet and exercise regime throughout study as recommended by counseling at study start.
  • Female subjects must have negative serum pregnancy test and must not be lactating. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method (i.e., sponge), or a double-barrier method of birth control (i.e., condom with spermicide) or abstinence must be used/ practiced throughout the study and for 90 days following the study.
  • 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 lab range), do not require contraception during the study.
  • Males with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study and for 90 days following the study. Male subjects must not donate sperm for 90 days following their participation in the study.

Exclusion Criteria:

  • Fasting blood glucose > than 140 mg/dL.
  • TSH level outside the normal range.
  • Creatinine > 1.5 times the upper limit of normal.
  • Liver function tests > 2 times the upper limit of normal.
  • Active or history of any significant medical condition including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
  • Patients with a history of the following:

    1. Uncontrolled hypertension;
    2. Diabetes requiring medical treatment;
    3. Major depressive disorder within the last 2 years;
    4. Any lifetime history of a suicide attempt;
    5. Any suicidal ideation/behavior in the last month;
    6. Other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder, severe eating disorders including bulimia).
  • A PHQ-9 score of ≥15.
  • Any suicidal ideation of type 4 or 5 on the C-SSRS.
  • Prior bariatric surgery.
  • History or close family history (parents or siblings) of melanoma.
  • Significant dermatologic findings as part of the Screening comprehensive skin evaluation performed by the dermatologist. Any concerning lesions identified during the screening period will be biopsied and results known to be benign prior to randomization. If the pre-treatment biopsy results are of concern, the patient will be excluded from the study.
  • Currently treated with anorectic agents or drugs in last 2 months from screening with anorexia as a frequent side event.
  • Taking more than 2 anti-hypertensive medications.
  • Acute illness or history of illness, which in the opinion of the Investigator, could pose a threat or harm to the patient or obscure interpretation of laboratory test results or interpretation of study data.
  • History of any malignancy, past or present, including skin cancer, multiple severely dysplastic nevi, or nevoid basal cell carcinoma.
  • History of HIV infection or Hepatitis B or C.
  • History of significant drug hypersensitivity or anaphylaxis.
  • History of hypersensitivity to proteins (e.g., allergy shots).
  • Any clinically significant abnormalities on screening laboratories as determined by the Investigator.
  • Abnormal 12-lead electrocardiogram (ECG) at screening, except minor deviations deemed to be of no clinical significance by the Investigator. QTcF must be < 450 ms.
  • Received any experimental drugs or devices or have participated in a clinical study within 30 days prior to dosing.
  • Blood donation greater than 500 mL within 60 days prior to screening or intent to donate up to 30 days after Final Study Visit.
  • Hospitalization for surgery within the 3 months prior to screening except for minor outpatient procedures, or any planned hospitalizations during the study period.
  • Poor venous access or inability to tolerate venipuncture.
  • Inability to attend all study visits or comply with protocol requirements including fasting and restrictions on concomitant medication intake.
  • Participation in weight loss programs during the study period, including nutritional supplements/ replacements other than as recommended by nutritional counseling provided at study start.
  • Use of prescription medications on a regular basis with the following exceptions:

    1. Contraceptives (must be on for ≥3 months);
    2. Hormone replacement therapy (must be on stable dose for ≥3 months);
    3. Antihypertensives (<2 medications on a stable dose for ≥ 30 days);
    4. Statins (dose must be ≤ half the maximum dose; must be on a stable dose ≥3 months);
    5. Thyroxin (stable dose for ≥ 30 days);
    6. The last use of any other prescription medication must have been greater than 5 half-lives for the specific medication or at least 14 days prior to randomization, whichever is longer.
  • Women who are pregnant or are breast feeding.
  • Previously randomized and dosed in this study or previously exposed to RM-493.
  • History of alcohol or drug abuse within 5 years of Screening Visit.
  • Any other reason, which in the opinion of the Investigator would confound proper evaluation of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02041195


Locations
United States, Texas
Dallas, Texas, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
Investigators
Study Director: Elizabeth Stoner, MD Rhythm Pharmaceuticals, Inc.

Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02041195     History of Changes
Other Study ID Numbers: RM-493-009
First Posted: January 20, 2014    Key Record Dates
Last Update Posted: May 5, 2015
Last Verified: April 2015

Keywords provided by Rhythm Pharmaceuticals, Inc.:
Overweight

Additional relevant MeSH terms:
Overweight
Body Weight
Signs and Symptoms