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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01235741
• Other study ID #: DFA104
• Status: Terminated
• Phase: Phase 2
• First received: November 2, 2010
• Last updated: March 26, 2015
• Start date: January 2011
• Est. completion date: September 2011

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 213
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Obesity

Intervention

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
Group B: Subcutaneous Injection-twice a day (BID): Placebo equivalent volumes to active doses.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Takeda Pharmaceuticals North America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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	No