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

This study has been terminated.
(Results from previous study DFA102 demonstrated neutralizing activity to metreleptin in invitro assay in 2 participants.)
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01235741
First received: November 2, 2010
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Obesity
Drug: Pramlintide+Metreleptin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population [ Time Frame: Day 1 up to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population [ Time Frame: Baseline to Month 6 Follow Up ] [ Designated as safety issue: Yes ]
    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).

  • Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population [ Time Frame: Week 1 to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Neutralizing Activity to Metreleptin at Early Termination or During Post Treatment Follow-Up - Intent to Treat Population Who Received Metreleptin [ Time Frame: Baseline to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population [ Time Frame: Screening to 6 Month Follow-Up ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population [ Time Frame: Screening to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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.

  • Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population [ Time Frame: Baseline to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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).

  • Mean Change From Baseline to Month 6 Follow-Up in Heart Rate - Intent to Treat Population [ Time Frame: Baseline up to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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).

  • Mean Change From Baseline to 6 Month Follow-Up in Fasting Plasma Glucose - Intent to Treat Population [ Time Frame: Baseline to 6 Month Follow-Up ] [ Designated as safety issue: Yes ]
    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).

  • Mean Change From Baseline to Month 6 Follow-Up in Insulin - Intent to Treat Population [ Time Frame: Baseline up to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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).

  • Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population [ Time Frame: Baseline up to Month 6 Follow-Up ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population [ Time Frame: Baseline up to Month 6 Follow-Up ] [ Designated as safety issue: No ]
    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.


Enrollment: 213
Study Start Date: January 2011
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01235741

Locations
United States, California
Research Site
Greenbrae, California, United States
Research Site
La Jolla, California, United States
United States, Colorado
Research Site
Denver, Colorado, United States
United States, Florida
Research Site
Winter Park, Florida, United States
United States, Illinois
Research Site
Chicago, Illinois, United States
United States, Louisiana
Research Site
Baton Rouge, Louisiana, United States
United States, Maryland
Research Site
Hyattsville, Maryland, United States
United States, Massachusetts
Research Site
Boston, Massachusetts, United States
United States, Missouri
Research Site
St. Louis, Missouri, United States
United States, Montana
Research Site
Butte, Montana, United States
United States, New York
Research Site
New York, New York, United States
United States, Oklahoma
Research Site
Tulsa, Oklahoma, United States
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States
United States, Texas
Research Site
Austin, Texas, United States
United States, Utah
Research Site
Salt Lake City, Utah, United States
United States, Virginia
Research Site
Arlington, Virginia, United States
Research Site
Norfolk, Virginia, United States
Research Site
Richmond, Virginia, United States
Sponsors and Collaborators
AstraZeneca
Takeda Pharmaceuticals North America, Inc.
Investigators
Study Director: Senior Vice President, Research & Development Amylin Pharmaceuticals, LLC.
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01235741     History of Changes
Other Study ID Numbers: DFA104
Study First Received: November 2, 2010
Results First Received: August 12, 2013
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Pramlintide
Metreleptin
Obesity
Amylin
Takeda

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Pramlintide
Islet Amyloid Polypeptide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Appetite Depressants
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014