A Study To Examine The Efficacy And Safety Of Pramlintide+Metreleptin In Obese Subjects

Study Overview
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Brief Summary
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Following screening, eligible subjects will be enrolled into a 6-week Low Calorie Diet (LCD) lead-in period. Subjects who lose at least 2% of their body weight at the end of the 6-week LCD lead-in period will be randomized to 1 of 2 treatment arms (pramlintide+metreleptin or placebo) to begin a 16-week treatment period during which the effect on body weight of treatment with pramlintide+metreleptin will be compared to placebo. Following the 16 week blinded core treatment period, subjects will discontinue study medication for a period of 12 weeks. Following the 12 week off-drug follow-up period, subjects in both groups will initiate a 12 week open-label treatment period with Pramlintide+Metreleptin. During the 12 week off-drug and 12 week open label treatment periods, subjects will continue to participate in a Lifestyle Intervention (LSI) program.

Official Title
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A Randomized, Double-Blind, Placebo-Controled, Multicenter Study To Examine The Efficacy And Safety Of Pramlintide+Metreleptin In Obese Subjects Following A Low-Calorie Diet Lead-In

Conditions
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Obesity

Intervention / Treatment
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* Drug: Pramlintide+Metreleptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is obese with a BMI ≥35 to ≤45 kg/m2. Has stable body weight (not varying by >5% within 3 months prior to study start). Meets certain requirements with respect to concomitant medications. Has not smoked or used nicotine-containing products for at least 12 months prior to study start. Exclusion Criteria: Has not been enrolled in a weight loss program within 2 months prior to study start.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Pramlintide+Metreleptin | Drug: Pramlintide+Metreleptin<br>* Group A: Subcutaneous Injection once a day (QD): Pramlintide 360 mcg+Metreleptin 5.0 mg for 1 week followed by Pramlintide 360 mcg+Metreleptin 5.0 mg twice a day (BID) for 15 weeks.<br>|
| Placebo Comparator: Group B<br>Placebo | Drug: Placebo<br>* Group B: Subcutaneous Injection-twice a day (BID): Placebo equivalent volumes to active doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population | Treatment-Emergent Adverse Events are defined as those with an onset date and time on or after the first dose of randomized study medication and on or before the last dose of randomized study medication. Post-treatment Adverse Events are defined as those with an onset date after the date of last dose (imputed if not available) of randomized study medication. Participants experiencing multiple episodes of a given adverse event are counted once. | Day 1 up to Month 6 Follow-Up | 
| Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population | Participants who received metreleptin were analyzed; no placebo treated participants were analyzed. Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Leptin was measured in nanograms per milliliter (ng/mL). | Baseline to Month 6 Follow Up | 
| Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Anti-leptin antibodies measured at Weeks 1 and 2 of drug treatment, early termination visit, and at Months 2, 4, and 6 post treatment follow-up in participants who received metreleptin. | Week 1 to Month 6 Follow-Up | 
| Number of Participants With Neutralizing Activity to Metreleptin at Early Termination or During Post Treatment Follow-Up - Intent to Treat Population Who Received Metreleptin | In vitro assays were conducted to determine if neutralizing activity to metreleptin developed in participants treated with at least one dose of the drug during the study. Baseline is Day 1 of the Randomization Period, prior to administration of metreleptin. | Baseline to Month 6 Follow-Up | 
| Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Criteria for laboratory values of potential clinical importance for obese and overweight (BMI >= 25 kg/m^2) participants: Platelets high (H) >500,000/µL; low (L) <75,000/µL. Hematocrit males <36%, females <30%. Hemoglobin males <12 g/dL, females <10 g/dL. White blood cell count (WBC) H >18,000/µL; L <1,500/µL. Urine protein H >= 3+ or >= 500 mg/dL. Urine glucose H >= 3+ or >= 500 mg/dL. Urine ketones >= 3+ or Large. | Screening to 6 Month Follow-Up | 
| Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Criteria for laboratory values of potential clinical importance for obese and overweight (BMI >= 25 kg/m^2) participants: Total bilirubin High (H) > 2 mg/dL; Plasma or serum glucose fasting or non-fasting H > 200 mg/dL, low (L) < 60 mg/dL; Albumin L <2.5 g/dL; Creatine kinase H > 3*Upper limit of Normal (ULN); Sodium L <130 milliequivalents per liter (mEq/L), H > 150 mEq/L; potassium L<3.0 mEq/L, H> 5.5 mEq/L; bicarbonate L<18 mEq/L, H>35 mEq/L;calcium L <8mg/dL, H> 11 mg/dL; triglycerides H> 500 mg/dL; Cholesterol L < 100 mg/dL, H > 350 mg/dL; Alkaline phosphatase H > 3*ULN; Gamma-glutamyltransferase H>3*ULN; creatinine males > 1.6 mg/dL, females > 1.4 mg/dL; alanine aminotransferase H > 3*ULN; aspartate aminotransferase H > 3*ULN; urea nitrogen H > 45 mg/dL; uric acid males > 10.0 mg/dL, females > 8.0 mg/dL; Phosphorus L < 1.0 mg/dL H > 6.0 mg/dL. | Screening to Month 6 Follow-Up | 
| Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow-up was up to 6 months post treatment. Blood pressure included systolic and diastolic pressures measured in millimeters of mercury (mmHg). | Baseline to Month 6 Follow-Up | 
| Mean Change From Baseline to Month 6 Follow-Up in Heart Rate - Intent to Treat Population | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Heart rate was measured in beats per minute (beats/min). | Baseline up to Month 6 Follow-Up | 
| Mean Change From Baseline to 6 Month Follow-Up in Fasting Plasma Glucose - Intent to Treat Population | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Fasting glucose measured in milligrams per deciliter (mg/dL). | Baseline to 6 Month Follow-Up | 
| Mean Change From Baseline to Month 6 Follow-Up in Insulin - Intent to Treat Population | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Insulin measured in milliunits per liter (mU/L). | Baseline up to Month 6 Follow-Up | 
| Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Lipids measured included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides. Lipids were measured in milligrams per deciliter (mg/dL). | Baseline up to Month 6 Follow-Up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. | Baseline up to Month 6 Follow-Up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pramlintide, Metreleptin, Obesity, Amylin, Takeda