A Phase 2A, Randomized, Controlled, Double-Blind, Multicenter Study to Evaluate the Safety, Tolerability, and Effect on Body Weight of Recombinant-Methionyl Human Leptin Administered in Conjunction With Pramlintide in Overweight and Obese Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 177
- 试验地点
- 1
- 主要终点
- Mean Absolute Change From Baseline to Week 16 in Body Weight - Evaluable Population
研究概览
简要总结
This study will evaluate the safety, tolerability, and effect on body weight of leptin, injected subcutaneously, in combination with pramlintide, injected subcutaneously.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is obese (Body Mass Index [BMI]>=30kg/m^2 and <=35kg/m^2); or overweight (BMI>=27kg/m^2 and <30kg/m^2) with abdominal obesity, based on the following: *waist circumference >102 cm if male, *waist circumference >88 cm if female
- •Is a nonsmoker (has not smoked for at least 6 months prior to the study)
- •Consumes a morning and evening meal each day
排除标准
- •Is diagnosed with type 2 diabetes
- •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 any of the following medications: *antiobesity agents (prescription or over-the-counter), *antipsychotic agents, *antiepileptic agents, *antidepressant agents, *drugs that directly affect gastrointestinal motility
- •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 previously received treatment with recombinant leptin or pramlintide
研究组 & 干预措施
Placebo and Metreleptin
Placebo-pramlintide 600 microliters (µL) twice a day (BID) and metreleptin (recombinant-methionyl human leptin) 5 milligram (mg) BID, 20 weeks
干预措施: metreleptin (Drug)
Placebo and Metreleptin
Placebo-pramlintide 600 microliters (µL) twice a day (BID) and metreleptin (recombinant-methionyl human leptin) 5 milligram (mg) BID, 20 weeks
干预措施: placebo-pramlintide 600 uL (Drug)
Pramlintide Acetate and Placebo
Lead-in period: 2 weeks pramlintide acetate 180 mcg BID, then 2 weeks pramlintide acetate 360 mcg BID Study period: Pramlintide acetate 360 mcg BID and placebo-metreleptin 1 mL BID, 20 weeks
干预措施: pramlintide acetate 360 mcg (Drug)
Pramlintide Acetate and Placebo
Lead-in period: 2 weeks pramlintide acetate 180 mcg BID, then 2 weeks pramlintide acetate 360 mcg BID Study period: Pramlintide acetate 360 mcg BID and placebo-metreleptin 1 mL BID, 20 weeks
干预措施: placebo-metreleptin 1 mL (Drug)
Pramlintide Acetate and Metreleptin
Lead-in period: 2 weeks pramlintide acetate 180 mcg BID, then 2 weeks pramlintide acetate 360 mcg BID Study period: Pramlintide acetate 360 mcg BID and metreleptin (recombinant-methionyl human leptin) 5 mg BID, 20 weeks
干预措施: pramlintide acetate 360 mcg (Drug)
Pramlintide Acetate and Metreleptin
Lead-in period: 2 weeks pramlintide acetate 180 mcg BID, then 2 weeks pramlintide acetate 360 mcg BID Study period: Pramlintide acetate 360 mcg BID and metreleptin (recombinant-methionyl human leptin) 5 mg BID, 20 weeks
干预措施: metreleptin (Drug)
Lead-In Period
During the Lead-In Period before a participant was randomized to a study arm, the participant received 180 mcg pramlintide acetate twice a day (BID) for 2 weeks, followed by 360 mcg pramlintide acetate BID for 2 weeks (total of 4 weeks in the Lead-In Period).
干预措施: pramlintide acetate 360 mcg (Drug)
Lead-In Period
During the Lead-In Period before a participant was randomized to a study arm, the participant received 180 mcg pramlintide acetate twice a day (BID) for 2 weeks, followed by 360 mcg pramlintide acetate BID for 2 weeks (total of 4 weeks in the Lead-In Period).
干预措施: Pramlintide acetate 180 mcg (Drug)
结局指标
主要结局
Mean Absolute Change From Baseline to Week 16 in Body Weight - Evaluable Population
时间窗: Baseline to Week 16
Absolute change in body weight as measured in kilograms (kg) from baseline to Week 16. Baseline defined as Day 1 of randomized treatment.
次要结局
- LS Mean Percent Change in Body Weight From Baseline to Weeks 4, 8, 12, 16, and 20 - Evaluable Population(Baseline up to Week 20)
- LS Mean Absolute Change From Baseline to Weeks 4, 8, 12, 20 in Body Weight - Evaluable Population(Baseline to Week 20)
- LS Mean Absolute Change in Body Weight From Enrollment to Weeks 4, 8, 12, 16, and 20 - Evaluable Population(Enrollment to Week 20)
- LS Mean Percent Change in Body Weight From Enrollment to Weeks 4, 8, 12, 16, and 20 - Evaluable Population(Enrollment to Week 20)
- Initial, Late, and Overall Rates of LS Mean Absolute Change in Body Weight From Day 1 to Week 20 - Evaluable Population(Baseline to Week 20)
- Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Weeks 16 and 20, and Number of Participants With Sustained Weight Loss in Each Category - Evaluable Population(Baseline to Weeks 16 and Weeks 20)
- LS Mean Percent Change in Weight From Enrollment to Baseline and LS Mean Percent Change in Excess Weight From Enrollment to Baseline - Evaluable Population(Enrollment to Baseline)
- LS Mean Absolute Change in Waist Circumference From Enrollment to Weeks 4, 8, 12, 16, 20 - Evaluable Population(Enrollment to Week 20)
- LS Mean Absolute Change in Waist Circumference From Baseline to Weeks 4, 8, 12, 16, 20 - Evaluable Population(Baseline to Week 20)
- LS Mean Absolute Change in Hip Circumference From Screening up to Week 20 - Evaluable Population(Screening up to Week 20)
- Number of Participants With BMI Change From Enrollment to Week 16 - Evaluable Population(Enrollment up to Week 16)
- Number of Participants With BMI Change From Enrollment to Week 20 - Evaluable Population(Enrollment up to Week 20)
- Mean Absolute Change From Enrollment to Week 16 in Fasting Glucose and Lipids - Evaluable Population(Enrollment to Week 16)
- Mean Absolute Change From Enrollment to Baseline, Weeks 4 and 16 in Fasting Total Leptin Concentration - Evaluable Population(Enrollment to Week 16)
- Mean Absolute Change From Enrollment to Baseline and Week 16 in Fasting Total Amylin -Evaluable Population(Enrollment to Week 16)
- Mean Absolute Change From Enrollment to Baseline and Week 16 in Fasting Total Insulin - Evaluable Population(Enrollment to Week 16)
- LS Mean Absolute Change From Enrollment to Week 16 in Patient Reported Outcome (PRO) Instruments Measuring Quality of Life and Mood - Evaluable Population(Enrollment to Week 16)
- LS Mean Absolute Change From Enrollment to Week 16 in Patient Reported Outcomes (PRO) for Eating Behavior - Evaluable Population(Enrollment to Week 16)
- LS Mean Absolute Change From Enrollment to Week 16 in Hospital Anxiety and Depression Scale (HADS) - Evaluable Population(Enrollment to Week 16)
- Mean Absolute Change From Enrollment to Week -2, Week 16 and Week 20 in Systolic and Diastolic Blood Pressure - Enrolled Population(Enrollment up to Week 20(Randomized Group) or Enrollment up to, not including Day 1(Non-Randomized Group))
- Absolute Change From Enrollment to Week -2, Week 16 and Week 20 in Heart Rate - Enrolled Population(Enrollment up to Week 20(Randomized Group) or Enrollment up to, not including Day 1(Non-Randomized Group))
- Number of Chemistry Values of Potential Clinical Importance - Enrolled Population(Enrollment up to Week 20(Randomized Group) or Enrollment up to, not including Day 1(Non-Randomized Group))
- Number of Participants With Clinically Significant Abnormal ECG at Weeks 16, 20, or Early Termination - Randomized Population(Weeks 16, 20, early termination)
- Number of Participants With Treatment-emergent Anti-Leptin Antibodies by Week 4, Week 8, Week 12, Week 16 - Intent to Treat Population(Baseline up to Week 16)
- Number of Hematology and Urinalysis Values of Potential Clinical Importance - Enrolled Population(Enrollment up to Week 20(Randomized Group) or Enrollment up to, not including Day 1(Non-Randomized Group))