A Thorough QTc Evaluation of the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants: A Randomized, Double-blind, Placebo-controlled, 3-arm Parallel Study With a Nested Crossover Design for Positive Control With Moxifloxacin Administration
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
研究概览
简要总结
This study will investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants.
详细描述
This study will be a randomized, double-blind, placebo-controlled 3-arm parallel study with a nested crossover design for positive control with moxifloxacin administration in healthy male and female participants.
Participants will be randomized to receive treatment with either cotadutide during the 13-week treatment period (Arm 1) or cotadutide-placebo (Arm 2).
The cotadutide-placebo treatment arm will be further divided into 2 subgroups (Arms 2A and 2B), in a nested crossover design for only the placebo-treated participants.
Participants will be randomized in a 2:1:1 ratio to Arm 1, Arm 2A, and Arm 2B.
Approximately 80 participants will be randomized to have 64 evaluable participants in the study.
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
- 是
入选标准
- •Healthy male and female participants of age 18 to 55 years.
- •Females must have a negative pregnancy test.
- •Have a Body Mass Index (BMI) of ≥ 18 and ≤ 29.9 kg/m^2.
排除标准
- •History or presence of any clinically significant disease or disorder.
- •History or presence of gastrointestinal, hepatic or renal disease, or any other condition (including gastrointestinal surgery) known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •History of acute or chronic pancreatitis.
- •Family history of sudden cardiac death before the age of 50 of a first-degree relative.
- •History of additional risk factors for Torsade de Pointes (eg, heart failure, clinically important bradycardia and electrolyte disturbances eg, hypokalemia, hypocalcemia, hypomagnesemia or family history of long QT syndrome).
- •History of neoplastic disease
- •Any clinically significant abnormalities in clinical chemistry, hematology, urinalysis results or vital signs.
- •Any clinically significant abnormalities in rhythm, conduction, or morphology of the 12-lead resting electrocardiogram (ECG).
- •Any positive result on screening for serum hepatitis B surface antigen OR anti-HBc antibody, indicative of active hepatitis B (ie, participants with positive anti-HBc antibody result are acceptable if anti HBc IgM antibodies are negative), hepatitis C antibody, and Human immunodeficiency virus (HIV) antibody.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes).
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- •Use of drugs with enzyme-inducing properties such as St John's Wort.
- •Participant has a positive test result for SARS-CoV-2 RT-PCR during screening period or at baseline.
- •Participant has clinical signs and symptoms consistent with COVID-19 or a history of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
研究组 & 干预措施
Arm 1
Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93.
干预措施: Cotadutide (Drug)
Arm 1
Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93.
干预措施: Moxifloxacin-placebo (Drug)
Arm 2A
Participants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93.
干预措施: Cotadutide-placebo (Drug)
Arm 2A
Participants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93.
干预措施: Moxifloxacin (Drug)
Arm 2A
Participants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93.
干预措施: Moxifloxacin-placebo (Drug)
Arm 2B
Participants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93.
干预措施: Cotadutide-placebo (Drug)
Arm 2B
Participants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93.
干预措施: Moxifloxacin (Drug)
Arm 2B
Participants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93.
干预措施: Moxifloxacin-placebo (Drug)
结局指标
主要结局
Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
时间窗: Up to Day 92
Time-matched change-from-baseline QTcF after cotadutide administration compared with placebo will be assesed using a C-QTc interval analysis. The method that removes the HR dependence of the QT interval most efficiently will be chosen as the primary correction method and its corresponding change from baseline QTc will be the primary endpoint.
次要结局
- Time to reach maximum observed plasma concentration (tmax) of cotadutide(Day 57 and Day 91)
- Change from baseline in QRS interval(From Day 2 up to Day 92 or early discontinuation)
- Change from baseline in QTcF(Up to Day 94)
- Change from baseline in Heart rate (HR)(From Day 2 up to Day 92 or early discontinuation)
- Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide(Day 57 and Day 91)
- Maximum observed plasma concentration (Cmax) of cotadutide(Day 57 and Day 91)
- Change from baseline in mean diastolic blood pressure (DBP)(Up to Day 92)
- Change from baseline in mean HR(Up to Day 92)
- Placebo-corrected mean change from baseline in HR(Up to Day 92)
- Number of participants with Antidrug Antibodies to cotadutide(Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose))
- Change from baseline in PR interval(From Day 2 up to Day 92 or early discontinuation)
- Number of participants with significant change in QRS interval(From Day 2 up to Day 92 or early discontinuation)
- Number of treatment-emergent changes in U-waves presence(From Day 2 up to Day 92 or early discontinuation)
- Number of participants with significant change in PR interval(From Day 2 up to Day 92 or early discontinuation)
- Number of treatment-emergent changes in T-wave morphology(From Day 2 up to Day 92 or early discontinuation)
- Placebo-corrected mean change from baseline in DBP(Up to Day 92)
- Number of participants with significant change in SBP(Up to Day 92)
- Number of participants with significant change in QTcF(From Day 2 up to Day 92 or early discontinuation)
- Number of participants with significant change in HR(Up to Day 92)
- Area under concentration-time curve in the dose interval (AUCtau) of cotadutide(Day 57 and Day 91)
- Number of participants with change in DBP(Up to Day 92)
- Placebo-corrected mean change from baseline in SBP(Up to Day 92)
- Number of participants with Adverse Events (AEs)(Up to follow-up visit 28 days post last dose (approximately Day 120))
- Change from baseline in mean systolic blood pressure (SBP)(Up to Day 92)