NCT06132841已完成1 期
A Phase I Randomized, Single-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 Following Repeat Dose Administration in Participants With Overweight or Obesity
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 104
- 试验地点
- 3
- 主要终点
- Number of participants with Adverse Events (AEs) and Serious Adverse Events(SAE)
研究概览
简要总结
A study in healthy male and female participants of non-childbearing and childbearing potential who have overweight or obesity
详细描述
The study will comprise of:
- A Screening Period of maximum 32 days (from Day -35 to Day -3).
- A Treatment Period of 6 weeks (Cohort 1), 12 weeks (Cohort 2 and 3) and 26 weeks (Cohort 4) during which the participants will receive the study drug during residency at clinical unit.
- A Follow-up Visit after the last dose of study drug.
This study with repeated dosing of AZD6234 consists of 4 cohorts. For cohorts 1,2 and 3, eligible participants will be randomized to AZD6234 and placebo in a 3:1 ratio. For Cohort 4, eligible participants will be randomized in a 4:1:4:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 142 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:
- •Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
- •Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
- •Have a BMI between 25 and 40 kg/m2 inclusive (at the time of screening) and weigh at least 60 kg.
- •Participant must have an evaluable, pre-randomization MRI, as confirmed by the core laboratory review (Cohort 4 only).
- •Cohort 4 only: Females of childbearing potential who use adequate protection (oral contraceptives are not permitted).
排除标准
- •History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- •History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal STT wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
- •Known or suspected history of drug abuse, smoking, alcohol abuse or cotinine at screening.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD
- •Has received prescription or non-prescription medication for weight loss within the last 3 months.
- •Self-reported weight change of > 5 kg in the last 3 months prior to screening.
- •Previous or planned (within study period) bariatric surgery or fitting of a weight loss device (eg, gastric balloon or duodenal barrier).
- •Participants who follow vegan diet or have medical dietary restrictions.
- •Participants who cannot communicate reliably with the Investigator.
- •Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- •Contra-indication to MRI: such as participants with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field; participants with history of extreme claustrophobia or participant cannot fit inside the MRI scanner cavity (Cohort 4 only).
研究组 & 干预措施
Cohort 2
Experimental
Participants will receive repeated doses of AZD6234 or placebo via SC injection
干预措施: AZD6234 (Drug)
Cohort 4
Experimental
Japanese participants with childbearing potential will receive repeated doses of AZD6234 or placebo via SC injection.
干预措施: AZD6234 (Drug)
Cohort 3
Experimental
Japanese participants will receive repeated doses of AZD6234 or placebo via SC injection
干预措施: AZD6234 (Drug)
Cohort 1
Experimental
Participants will receive repeated doses of AZD6234 or placebo via SC injection
干预措施: Placebo (Drug)
Cohort 2
Experimental
Participants will receive repeated doses of AZD6234 or placebo via SC injection
干预措施: Placebo (Drug)
Cohort 3
Experimental
Japanese participants will receive repeated doses of AZD6234 or placebo via SC injection
干预措施: Placebo (Drug)
Cohort 4
Experimental
Japanese participants with childbearing potential will receive repeated doses of AZD6234 or placebo via SC injection.
干预措施: Placebo (Drug)
Cohort 1
Experimental
Participants will receive repeated doses of AZD6234 or placebo via SC injection
干预措施: AZD6234 (Drug)
结局指标
主要结局
Number of participants with Adverse Events (AEs) and Serious Adverse Events(SAE)
时间窗: From Screening (Day -35 to Day -3) to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
The safety and tolerability of repeated subcutaneous (SC) doses of AZD6234 compared to placebo will be assessed.
次要结局
- Prevalence of anti-drug antibodies (ADAs) to AZD6234(Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) or to Day 183 (Cohort 4))
- Maximum observed plasma drug concentration (Cmax)(From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4))
- Area under the plasma concentration-time (AUClast)(From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4))
- Area under plasma concentration-time curve from zero to infinity (AUCinf)(From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or Day 225 (Cohort 4))
- Area under concentration time curve in the dosing interval (AUCtau)(From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4))
- Change from baseline in body weight of participants(From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4))
- Change from baseline in Body Mass Index (BMI) of participants(From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4))
- Percentage change from baseline in fasting insulin(From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4))
- Change from baseline in absolute level of fasting insulin of participants(From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4))
- Incidence of ADAs to AZD6234(Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) to Day 183 (Cohort 4))
- ADA titer(Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) or to Day 183 (Cohort 4))
研究者
研究点 (3)
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