A Phase 1 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Cotadutide in Chinese Overweight/Obese Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
A Phase 1 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Cotadutide in Overweight/Obese Subjects with Chinese ancestry with Type 2 Diabetes Mellitus
详细描述
This is a randomized, double-blinded, placebo-controlled study designed to evaluate the safety, tolerability, PK and efficacy of ascending doses of cotadutide in overweight or obese subjects with T2DM. This study will enroll subjects aged 18 to 74 years with a body mass index (BMI) ≥ 25 and ≤ 35 kg/m2. Subjects will have a diagnosis of T2DM and inadequate blood glucose control as defined by a HbA1c of 7% to 8.5%, and will be on metformin monotherapy in the three months prior to screening. Total 16 Chinese subjects will be randomized to cotadutide or placebo in a 3:1 ratio (cotadutide [n=12] and placebo [n=4]) at multicentre in China mainland. Those subjects who receive cotadutide once daily SC will be titrated to a maximum of 600 μg once daily SC, beginning at 50 μg once daily SC. The study has about 2 weeks screening period, a run-in period of 10 days and an up to 7-week up-titration treatment period followed by a 3-week treatment extension period at the dose of 600 μg and followed by a 28-day follow-up period.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Placebo
Placebo: Placebo subcutaneous injection
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Baseline until the follow-up period (28 days post last dose), 98 days in total
To assess the safety and tolerability of Cotadutide
Incidence of treatment-emergent serious adverse events (TESAEs)
时间窗: Baseline until the follow-up period (28 days post last dose), 98 days in total
To assess the safety and tolerability of Cotadutide
Time to Cmax (tmax)
时间窗: Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.
To characterize the PK profile of Cotadutide
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
时间窗: Baseline until the follow-up period (28 days post last dose), 98 days in total
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals as measured by digitial 12-lead ECG.
Number of participants with abnormal vital signs reported as TEAEs
时间窗: Baseline until the follow-up period (28 days post last dose), 98 days in total
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital sign parameters (Systolic Blood Pressure, Diastolic Blood Pressure, Pulse, Respiration rate, body temperature).
Number of Participants With Abnormal Physical Examinations Reported as TEAEs
时间窗: Baseline until the follow-up period (28 days post last dose), 98 days in total
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and enocrine.
Area under the concentration-time curve (AUC) during the dosing interval (AUCtau)
时间窗: Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.
To characterize the PK profile of Cotadutide
Maximum observed concentration (Cmax)
时间窗: Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.
To characterize the PK profile of Cotadutide
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
时间窗: Baseline until the follow-up period (28 days post last dose), 98 days in total
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urinalysis.
Trough plasma concentration (Ctrough)
时间窗: Day 1 of Up-titration treatment period through 3 days post lost dose, total of up to 73 days.
To characterize the PK profile of Cotadutide
次要结局
- Change in daily average glucose levels(baseline to the end of extension period, and during 14 days of the follow up period, 84 days in total.)
- Change in percentage time spent in hyperglycemia (> 140 mg/dL) over 24hours and over 7days(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period)
- Change in fasting plasma glucose (mg/dL)(Baseline through 21day treatment extension period, 70 days in total)
- Change in HbA1c(Baseline through 21day treatment extension period, 70 days in total)
- Anti-drug antibodies (ADAs) to Cotadutide(Day 1 of Up-titration treatment period through end of study, 98 days in total)
- Change in 7-day average glucose levels(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period)
- Absolute change in body weight(Baseline through 21day treatment extension period, 70 days in total)
- Proportion of subjects achieving > 5% body weight loss(Baseline through 21day treatment extension period, 70 days in total)
- Change in percentage time spent in target range (70 -140 mg/dL) over 24hours and over 7days(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period)
- Change in percentage time spent in the range (< 54 mg/dL) over 24hours and over 7days(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period)
- Change in estimated hemoglobin A1c (HbA1c)(Baseline through 21day treatment extension period, 70 days in total)
- Percentage change in body weight(Baseline through 21day treatment extension period, 70 days in total)
- Change in coefficient of variation as measured by CGM over 7 days(Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49 of the up-titration period, Days 50-56, Days 57-63, Days 64 - 70 of the treatment extension period)