A Phase 1b, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 598 in Subjects With Obesity
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings
研究概览
简要总结
The main objective of this study is to assess the safety and tolerability of multiple doses of AMG 598 administered alone or in combination with liraglutide in adults with obesity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind study
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
- •Men and women with ages between 18 and 65 years old, inclusive, at time of signing consent
- •Body mass index (BMI) between greater than or equal to 30.0 kg/m^2 and less than or equal to 40.0 kg/m^2 at screening
- •Except for obesity, otherwise healthy or medically stable per protocol
- •Have a stable body weight defined as less than 5 kg self-reported change during the previous 8 weeks prior to screening
- •Other Inclusion criteria may apply
- •Stable on liraglutide, depending on cohort
排除标准
- •History or clinical evidence of diabetes
- •Inadequate organ function at screening
- •Currently receiving treatment in another investigational device or drug study
- •Women who are pregnant/lactating/breastfeeding or who plan to become pregnant/breastfeed while on study through 5 months after receiving the last dose of investigational product
- •History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
- •A family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2; a personal history of non-familial medullary thyroid carcinoma; confirmed chronic pancreatitis or idiopathic acute pancreatitis, or gallbladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy, for cohorts receiving liraglutide
- •History of major depressive disorder
- •Other Exclusion criteria may apply
研究组 & 干预措施
Placebo
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.
干预措施: Placebo (Drug)
Placebo + Liraglutide
Participants received placebo subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: Placebo (Drug)
Placebo + Liraglutide
Participants received placebo subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: Liraglutide (Drug)
AMG 598 70 mg
Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks (Q4W) for a total of 3 doses.
干预措施: AMG 598 (Drug)
AMG 598 70 mg + Liraglutide
Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: AMG 598 (Drug)
AMG 598 70 mg + Liraglutide
Participants received 70 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: Liraglutide (Drug)
AMG 598 210 mg
Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.
干预措施: AMG 598 (Drug)
AMG 598 210 mg + Liraglutide
Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: AMG 598 (Drug)
AMG 598 210 mg + Liraglutide
Participants received 210 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: Liraglutide (Drug)
AMG 598 420 mg
Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses.
干预措施: AMG 598 (Drug)
AMG 598 420 mg + Liraglutide
Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: AMG 598 (Drug)
AMG 598 420 mg + Liraglutide
Participants received 420 mg AMG 598 by subcutaneous injection once every 4 weeks for a total of 3 doses in addition to liraglutide administered by subcutaneous injection once a day for 12 weeks. The starting dose of liraglutide was 0.6 mg/day, increasing in increments of 0.6 mg/day every 7 days to reach the full dosage of 3 mg/day by week 5.
干预措施: Liraglutide (Drug)
结局指标
主要结局
Number of Participants With TEAEs Due to Laboratory, Electrocardiogram, and Vital Sign Findings
时间窗: 207 days
TEAEs due to laboratory, electrocardiogram (ECG) and vital sign findings include any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or electrocardiogram, or vital signs measurements, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator (ie, not related to progression of underlying disease).
Number of Participants With Treatment-emergent Adverse Events
时间窗: 207 days
The investigator assessed the severity of each adverse event reported during the study. The assessment was based on the Amgen Standard Grading Scale: Mild: Aware of sign or symptom, but easily tolerated. Moderate: Discomfort enough to cause interference with usual activity. Severe: Incapacitating with inability to work or do usual activity. A Serious adverse event is defined as any untoward medical occurrence that, met at least 1 of the following serious criteria * Death; * Was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Other medically important serious event. The investigator also assessed whether each adverse event was related to study drug administration based on clinical judgement.
次要结局
- Area Under the Concentration-time Curve From Time 0 to 28 Days (AUC0-28) for AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85)
- Maximum Observed Concentration (Cmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207)
- Time to Maximum Observed Concentration (Tmax) of AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207)
- Dose-normalized Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207)
- Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of AMG 598 After Subcutaneous Injection on Day 57(Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207)
- Accumulation Ratio (AR) for Cmax of AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207)
- Accumulation Ratio of AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85)
- Dose-normalized AUC0-28 for AMG 598 After Subcutaneous Injection on Day 1 and Day 57(Day 1, predose, and days 6, 8, 15, 22, and 29; Day 57 predose and days 62, 64, 71, and 85)
- Terminal Half-life (T1/2,z) of AMG 598 After Subcutaneous Injection on Day 57(Day 57 predose and days 62, 64, 71, 85, 99, 113, 127, 169, and 207)