Clinical trial NCT00673387: Study to Examine Safety, Tolerability, and Effect on Body Weight of Metreleptin Administered in Conjunction With Pramlintide in Obese and Overweight Subjects
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Examine the Safety, Tolerability, and Effect on Body Weight of Metreleptin Administered in Conjunction With Pramlintide in Obese and Overweight Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Overweight
Obesity
Keywords: overweight
obesity
pramlintide
metreleptin
Amylin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-05-07
Enrollment: 636
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: A randomized, double-blind, placebo-controlled, dose-ranging study to examine the safety, tolerability and effect on body weight of a range of doses of metreleptin and pramlintide, each administered by a separate subcutaneous (SC) injection in obese and overweight subjects.


Eligibility criteria: Inclusion Criteria:

* 18 to 65 years old.
* Is obese (Body Mass Index \[BMI\]\>=30kg/m\^2 and \<=35kg/m\^2); or overweight (BMI\>=27kg/m\^2 and \<30kg/m\^2.
* Has stable body weight, i.e., not varying by \>3% within 3 months prior to study.
* Has not been treated over the past 3 months or is currently treated with any of the following medications: Oral contraceptives (female subjects); Hormone replacement therapy (female subjects); Metformin for the treatment of polycystic ovary syndrome (female subjects); Antihypertensive agents; Lipid-lowering agents; Thyroid replacement therapy; selective serotonin reuptake inhibitors (SSRIs).
* Is comfortable with having repeated telephone contacts with a lifestyle counselor during the study.
* Is a nonsmoker (has not smoked for at least 6 months prior to the study).

Exclusion Criteria:

* Has a medical history (e.g., morbid childhood obesity) and/or physical characteristics suggestive of genetic obesity or syndromatic obesity (e.g., Prader-Willi syndrome, Bardet-Biedl syndrome).
* Is currently enrolled or plans to enroll in a diet, weight loss, or exercise program with the specific intent of losing weight (subjects who have been following an exercise regimen resulting in stable weight maintenance for at least 2 months prior to enrollment are eligible for study inclusion)
* Has been treated over the past 2 months, is currently treated, or is expected to require or undergo treatment with \*antiobesity agents (prescription or over-the-counter), \*antipsychotic agents, \*antiepileptic agents, \*antidepressant agents, \*drugs that directly affect gastrointestinal motility, \*antidiabetic medications.
* Has previously received treatment with metreleptin or pramlintide in a clinical study or has received prior treatment with pramlintide (SYMLIN®).
* Has received any investigational drug within 30 days or within a period corresponding to 5 half-lives of that drug, whichever is greater, prior to this study starting.
* Has had a major surgery or a blood transfusion, or has donated blood over the past 2 months or is planning to donate blood during the study.
* Has had liposuction, abdominoplasty, or similar procedure over the past year or is planning to have such a procedure during the study.

Primary outcomes:
measure: Least Squares (LS) Mean Percent Change in Body Weight From Baseline to Week 28 - Evaluable Population
timeFrame: Baseline to Week 28
Secondary outcomes:
measure: Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population
timeFrame: Baseline to Week 28
measure: Mean Absolute Change From Baseline to Weeks 4, 12, 28 in Mean Trough Concentration of Total Leptin - Evaluable Population
timeFrame: Baseline to Week 28
measure: LS Mean Absolute Change in Body Weight From Baseline to Weeks 4, 12, and 28 - Evaluable Population
timeFrame: Baseline to Week 28
measure: LS Mean Change in Waist Circumference From Baseline to Week 12 and Week 28 - Evaluable Population
timeFrame: Baseline to Weeks 12 and Week 28
measure: Geometric Mean of the Total Area Under the Concentration Time Curve (AUC) From Time 0 to Last Quantifiable Concentration (Tlast) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide
timeFrame: Week 4 and Week 24
measure: Geometric Mean of AUC From Time 0 to Infinity for Pramlintide at Weeks 4 and 24 - Evaluable Population Treated With Pramlintide
timeFrame: Weeks 4 and 24
measure: Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide
timeFrame: Week 4 and Week 24
measure: Least Squares (LS) Mean Absolute Change From Baseline to Week 28 in Percent of Body Fat - Evaluable Population
timeFrame: Baseline to Week 28
measure: LS Mean Absolute Change From Baseline to Week 28 in Total Body Fat Mass (k) - Evaluable Population
timeFrame: Baseline to Week 28
measure: LS Mean Absolute Change From Baseline to Week 28 in Fat-free Mass (kg) - Evaluable Population
timeFrame: Baseline to Week 28
measure: LS Mean Absolute Change From Baseline to Week 28 in Fasting Plasma Glucose, Total Cholesterol (TC), Triglycerides, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol - Evaluable Population
timeFrame: Baseline to Week 28
measure: Mean Absolute Change From Baseline to Week 28 for Insulin - Evaluable Population
timeFrame: Baseline to Week 28
measure: Mean Absolute Change From Screening to Week 24 in Impact of Weight on Quality of Life Questionnaire-lite Version (IWQOL-Lite) Total Score - Evaluable Population
timeFrame: Screening to Week 24
measure: Mean Absolute Change From Screening to Week 24 in Binge Eating Scale (BES) Total Score - Evaluable Population
timeFrame: Screening to Week 24
measure: Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population
timeFrame: Screening to Week 24
measure: Mean Absolute Change From Screening to Week 24 in Hospital Anxiety and Depression Scale (HADS) Total Scores - Evaluable Population
timeFrame: Screening to Week 24
measure: Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population
timeFrame: Screening to Week 24
measure: Mean Absolute Change From Screening to Week 24 in Minutes to Fall Asleep, Hours of Sleep and The Pittsburgh Sleep Quality Index (PSQI) Global Score - Evaluable Population
timeFrame: Screening to Week 24
measure: Mean Absolute Change From Screening to Week 24 in the Epworth Sleepiness Scale (ESS) Total Score - Evaluable Population
timeFrame: Screening to Week 24
measure: Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population
timeFrame: Screening to Week 28
measure: Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population
timeFrame: Screening to Week 28
measure: Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 28 - Intent to Treat Population
timeFrame: Baseline to Week 28
measure: Mean Change in Heart Rate From Baseline to Week 28 - Intent to Treat Population
timeFrame: Baseline to Week 28
measure: Number of Participants With Treatment-emergent Positive Anti-leptin Antibody Titers at Week 28 - Intent to Treat Population
timeFrame: Baseline to Week 28
measure: Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population
timeFrame: Screening to Week 28 (or study termination)
measure: Mean Change From Screening to Week 28 in the Electrocardiogram Parameter of Heart Rate - Intent to Treat Population
timeFrame: Screening to Week 28 (or early termination)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Pembrook Pines
country: United States
facility: Research Site
state: Florida
city: Plantation
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Springfield
country: United States
facility: Research Site
state: Illinois
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Auburn
country: United States
facility: Research Site
state: Maine
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Edina
country: United States
facility: Research Site
state: Minnesota
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Butte
country: United States
facility: Research Site
state: Montana
city: New York City
country: United States
facility: Research Site
state: New York
city: Statesville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Eugene
country: United States
facility: Research Site
state: Oregon
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Anderson
country: United States
facility: Research Site
state: South Carolina
city: Greer
country: United States
facility: Research Site
state: South Carolina
city: Mt. Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Belingham
country: United States
facility: Research Site
state: Washington
city: Olympia
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Amylin Pharmaceuticals, LLC.
name: Vice President Research and Development, MD
role: STUDY_DIRECTOR
References:
citation: Chan JL, Koda J, Heilig JS, Cochran EK, Gorden P, Oral EA, Brown RJ. Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy. Clin Endocrinol (Oxf). 2016 Jul;85(1):137-49. doi: 10.1111/cen.12980. Epub 2016 Feb 2.