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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 636
- 试验地点
- 1
- 主要终点
- Least Squares (LS) Mean Percent Change in Body Weight From Baseline to Week 28 - Evaluable Population
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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^
- •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).
排除标准
- •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.
研究组 & 干预措施
Placebo-P + Metreleptin 5.0 mg
Placebo matched to pramlintide BID plus metreleptin 5.0 mg BID
干预措施: metreleptin (Drug)
Placebo-P + Placebo-M
Placebo matched to pramlintide BID plus placebo matched to metreleptin BID
干预措施: placebo-P (Drug)
Placebo-P + Placebo-M
Placebo matched to pramlintide BID plus placebo matched to metreleptin BID
干预措施: placebo-M (Drug)
Pramlintide 360 mcg + Placebo-M
360 mcg pramlintide given twice per day (BID) plus Placebo matched to Metreleptin given BID
干预措施: pramlintide acetate (Drug)
Pramlintide 360 mcg + Placebo-M
360 mcg pramlintide given twice per day (BID) plus Placebo matched to Metreleptin given BID
干预措施: placebo-M (Drug)
Placebo-P + Metreleptin 5.0 mg
Placebo matched to pramlintide BID plus metreleptin 5.0 mg BID
干预措施: placebo-P (Drug)
Pramlintide 180 mcg + Metreleptin 2.5 mg
Pramlintide 180 mcg BID plus Metreleptin 2.5 mg BID
干预措施: pramlintide acetate (Drug)
Pramlintide 180 mcg + Metreleptin 2.5 mg
Pramlintide 180 mcg BID plus Metreleptin 2.5 mg BID
干预措施: metreleptin (Drug)
Pramlintide 180 mcg + Metreleptin 5.0 mg
Pramlintide 180 mcg BID plus Metreleptin 5.0 mg BID
干预措施: pramlintide acetate (Drug)
Pramlintide 180 mcg + Metreleptin 5.0 mg
Pramlintide 180 mcg BID plus Metreleptin 5.0 mg BID
干预措施: metreleptin (Drug)
Pramlintide 360 mcg + Metreleptin 1.25 mg
Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID
干预措施: pramlintide acetate (Drug)
Pramlintide 360 mcg + Metreleptin 1.25 mg
Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID
干预措施: metreleptin (Drug)
Pramlintide 360 mcg + Metreleptin 2.5 mg
Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID
干预措施: pramlintide acetate (Drug)
Pramlintide 360 mcg + Metreleptin 2.5 mg
Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID
干预措施: metreleptin (Drug)
Pramlintide 360 mcg + Metreleptin 5.0 mg
Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID
干预措施: pramlintide acetate (Drug)
Pramlintide 360 mcg + Metreleptin 5.0 mg
Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID
干预措施: metreleptin (Drug)
结局指标
主要结局
Least Squares (LS) Mean Percent Change in Body Weight From Baseline to Week 28 - Evaluable Population
时间窗: Baseline to Week 28
Body weight was measured in kilogram (kg). Baseline is defined as Day 1. If Day 1 was missing or after the first dose date of randomized treatment, the last available value prior to Day 1 was used. Drug Randomization stratified by sex and 3 categories baseline BMI (12 arms); 3 treatment arms combined for summaries as single placebo treatment group; 3 combined for summaries as single pramlintide monotherapy treatment group (total: 8 treatment groups).
次要结局
- LS Mean Change in Waist Circumference From Baseline to Week 12 and Week 28 - Evaluable Population(Baseline to Weeks 12 and Week 28)
- Mean Absolute Change From Baseline to Week 28 for Insulin - Evaluable Population(Baseline to Week 28)
- Least Squares (LS) Mean Absolute Change From Baseline to Week 28 in Percent of Body Fat - Evaluable Population(Baseline to Week 28)
- Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population(Baseline to Week 28)
- Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population(Screening to Week 24)
- Mean Absolute Change From Screening to Week 24 in the Epworth Sleepiness Scale (ESS) Total Score - Evaluable Population(Screening to Week 24)
- Mean Absolute Change From Baseline to Weeks 4, 12, 28 in Mean Trough Concentration of Total Leptin - Evaluable Population(Baseline to Week 28)
- LS Mean Absolute Change in Body Weight From Baseline to Weeks 4, 12, and 28 - Evaluable Population(Baseline to Week 28)
- Geometric Mean of AUC From Time 0 to Infinity for Pramlintide at Weeks 4 and 24 - Evaluable Population Treated With Pramlintide(Weeks 4 and 24)
- 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(Baseline to Week 28)
- Mean Absolute Change From Screening to Week 24 in Hospital Anxiety and Depression Scale (HADS) Total Scores - Evaluable Population(Screening to Week 24)
- 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(Week 4 and Week 24)
- Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide(Week 4 and Week 24)
- LS Mean Absolute Change From Baseline to Week 28 in Total Body Fat Mass (k) - Evaluable Population(Baseline to Week 28)
- Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population(Screening to Week 24)
- Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population(Screening to Week 28 (or study termination))
- LS Mean Absolute Change From Baseline to Week 28 in Fat-free Mass (kg) - Evaluable Population(Baseline to Week 28)
- 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(Screening to Week 24)
- Mean Absolute Change From Screening to Week 24 in Binge Eating Scale (BES) Total Score - Evaluable Population(Screening to Week 24)
- Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population(Screening to Week 28)
- Mean Change in Heart Rate From Baseline to Week 28 - Intent to Treat Population(Baseline to Week 28)
- Number of Participants With Treatment-emergent Positive Anti-leptin Antibody Titers at Week 28 - Intent to Treat Population(Baseline to Week 28)
- 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(Screening to Week 24)
- Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population(Screening to Week 28)
- Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 28 - Intent to Treat Population(Baseline to Week 28)
- Mean Change From Screening to Week 28 in the Electrocardiogram Parameter of Heart Rate - Intent to Treat Population(Screening to Week 28 (or early termination))