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

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

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.

Study Overview

• Status: Terminated
• Conditions: Obesity
• Intervention / Treatment: Drug: Pramlintide+Metreleptin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Greenbrae, California, United States
      • Research Site
    • La Jolla, California, United States
      • Research Site
  • Colorado
    • Denver, Colorado, United States
      • Research Site
  • Florida
    • Winter Park, Florida, United States
      • Research Site
  • Illinois
    • Chicago, Illinois, United States
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States
      • Research Site
  • Maryland
    • Hyattsville, Maryland, United States
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Research Site
  • Missouri
    • St. Louis, Missouri, United States
      • Research Site
  • Montana
    • Butte, Montana, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
  • Oklahoma
    • Tulsa, Oklahoma, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Texas
    • Austin, Texas, United States
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States
      • Research Site
  • Virginia
    • Arlington, Virginia, United States
      • Research Site
    • Norfolk, Virginia, United States
      • Research Site
    • Richmond, Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; Pramlintide+Metreleptin	Drug: Pramlintide+Metreleptin; 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.
PLACEBO_COMPARATOR: Group B; Placebo	Drug: Placebo; Group B: Subcutaneous Injection-twice a day (BID): Placebo equivalent volumes to active doses.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Takeda Pharmaceuticals North America, Inc.
• Investigators: Study Director: Senior Vice President, Research & Development, Amylin Pharmaceuticals, LLC.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: November 2, 2010
• First Submitted That Met QC Criteria: November 4, 2010
• First Posted (ESTIMATE): November 7, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 15, 2015
• Last Update Submitted That Met QC Criteria: March 26, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Obesity; Amylin; Pramlintide; Metreleptin; Takeda
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Pramlintide
• Other Study ID Numbers: DFA104