Phase 2 Study to Evaluate Safety and Efficacy of Rm-493 in Obese Patients
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.
First received: December 11, 2012
Last updated: March 19, 2013
Last verified: March 2013
The purpose of this study is to evaluate the effects of RM-493 on mean percent body weight loss, and other weight loss parameters as well as Pharmacokinetic (PK) profile, and ambulatory blood pressure in obese patients. The study is designed to evaluate the efficacy and tolerability of a single dose of RM-493. The study drug (RM-493 and placebo) will be administered subcutaneously in a blinded fashion.
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
||A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of RM 493, a Melanocortin 4 Receptor (MC4R) Agonist in Obese Patients
Primary Outcome Measures:
Secondary Outcome Measures:
- Effect of RM-493 on loss of ≥5% of baseline body weight [ Time Frame: Day 1 though Day 90 ] [ Designated as safety issue: No ]
Proportion of patients who lose ≥5% of their baseline body weight
- Effect of RM-493 on Pharmacokinetics (PK) [ Time Frame: Day 1 through Day 90 ] [ Designated as safety issue: No ]
Day 1 at baseline compared to Day 1, 2 hours after dosing and Days 7, 14, 28, 56 and 90 during dosing. Samples will be obtained to assess steady state concentration throughout the dosing period.
- Safety and Tolerability of RM-493 [ Time Frame: Screening through Day 180 ] [ Designated as safety issue: Yes ]
Assessment of adverse events and clinical laboratory evaluations.
- Effect of RM-493 on ambulatory blood pressure monitoring parameters (ABPM) [ Time Frame: Day -6 and Day 28 ] [ Designated as safety issue: Yes ]
The effect of RM-493 on ambulatory blood pressure monitoring parameters (ABPM).
- Effect on mean percent weight loss, mean weight loss, and proportion of severely obese patients who lose ≥ 5% of their baseline body weight [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: No ]
Measurement of change in mean percent weight loss, mean weight loss, and proportion of severely obese (BMI ≥ 40 Kg/m²) patients who lose ≥ 5% of their baseline body weight
- Effect on mean body weight (BW) loss [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: No ]
Measurement of effect on mean body weight (BW) loss.
Other Outcome Measures:
- Effect of RM-493 on waist circumference [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: No ]
Measurement of change in waist circumference from Baseline to Day 90.
- Effect of RM-493 on body composition as measured by Dual Energy X-Ray Absorptiometry. [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: No ]
Measurement of change in body composition as assessed by Dual Energy X-Ray Absorptiometry (DXA) from Baseline to Day 90.
- Effect of RM-493 on hunger and satiety [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: No ]
Measurement of change in hunger and satiety as assessed using the Hunger and Satiety Visual Analog Scale (VAS) from Baseline to Day 90.
- Effect of RM-493 on quality of life [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: No ]
Measurement of the effect of RM-493 on the quality of life as assessed using the Impact of Weight on Quality of Life - Lite questionnaire (IWQOL-Lite) from Baseline to Day 90.
- Effect of RM-493 on depression/suicidality [ Time Frame: Baseline to Day 90 ] [ Designated as safety issue: Yes ]
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) from Baseline to Day 90.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2013 (Final data collection date for primary outcome measure)
Active Comparator: RM-493
Double blind RM-493 will be administered at a dose of 1mg/24hrs via subcutaneous infusion for 90 days.
Placebo Comparator: Placebo
Double blind placebo will be administered via subcutaneous infusion for 90 days.
|Ages Eligible for Study:
||18 Years to 65 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Be between the age of 18 and 65.
- 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: 35-50 Kg/m², inclusive. It is planned that approximately 20 of these patients will have a BMI ≥ 40 Kg/m².
- Stable body weight (+/- 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 that are intended to remain on a stable dose during the protocol.
- Willingness and demonstrates ability to self administer study medication subcutaneously via an infusion pump during the placebo practice period.
- Willing to maintain a healthy diet and exercise regime throughout study as recommended by counseling at study start.
- 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 completion of study treatment: 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. Patients must agree to practice the above birth control methods for 30 days after completion of study treatment 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 90 days 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.
- Fasting blood glucose > than 140 mg/dL.
- HbA1c ≥6.5%.
- 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:
- Uncontrolled hypertension;
- Diabetes requiring medical treatment, presently or in the past;
- Major depressive disorder within the last 2 years;
- Any lifetime history of a suicide attempt;
- Any suicidal behavior in the last month;
- 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.
- Treated with anorectic agents or drugs with anorexia as a frequent side event.
- Taking 3 or more 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 HIV infection.
- 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 or pre-dose (Day 1), except minor deviations deemed to be of no clinical significance by the Investigator. QTc must be < 450 ms.
- Received any experimental drugs or devices or have participated in a clinical study within 30 days prior to dosing.
- 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:
- Contraceptives (must be on for ≥3 months);
- Hormone replacement therapy (must be on stable dose for ≥3 months);
- 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749137
|Miami, Florida, United States |
|Lexington, Kentucky, United States |
|Rochester, New York, United States |
|Raleigh, North Carolina, United States |
|Dallas, Texas, United States |
|Renton, Washington, United States |
Rhythm Pharmaceuticals, Inc.
||Elizabeth Stoner, MD
||Rhythm Pharmaceuticals, Inc.
No publications provided
||Rhythm Pharmaceuticals, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 11, 2012
||March 19, 2013
||United States: Food and Drug Administration
Keywords provided by Rhythm Pharmaceuticals, Inc.:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 23, 2013
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