A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD1043 Following Single and Multiple Ascending Doses Via Subcutaneous and/or Intravenous Administration in Healthy Adult Participants Living With Overweight and/or Obesity.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 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), serious adverse events (SAEs), AE leading to discontinuation (DAEs), and AEs of special interest (AESIs)
研究概览
简要总结
The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD1043 following single and multiple ascending doses in healthy adult participants living with overweight and/or obesity, including participants of Japanese and Chinese descent.
详细描述
This is a phase 1, first time in human (FTiH) randomized, single-blind, placebo-controlled study in healthy male and female participants living with overweight and/or obesity, with female participants being of non-childbearing potential. It consists of 2 parts:
Part A (single ascending doses: SAD): This will consist of Part A1 (Global SAD (GSAD)) with 6 cohorts, Part A2 (Japanese SAD (JSAD)) with 2 cohorts and Part A3 (Chinese SAD (CSAD)) with 1 cohort.
Part B (multiple ascending doses: MAD): This will consist of Part B1 (Global MAD (GMAD)) with 3 cohorts and Part B2 (Japanese MAD (JMAD)) with 1 cohort.
Participants are only allowed to participate in one of the cohorts.
Both Part A and Part B will comprise of:
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
- Triple (Participant, Care Provider, Investigator)
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
- 是
入选标准
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- •Females of non-childbearing potential must be confirmed as postmenopausal or have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
- •Have a body mass index between 25 and 39.9 kg/m2 (Global cohorts [Parts A1 and B1]), or 23 and 39.9 kg/m2 (Japanese [Parts A2 and B2] and Chinese [Part A3] cohorts) inclusive and weigh at least 50 kg.
- •For the Parts A2 and B2, participants should be Japanese (natives of Japan or Japanese Americans), having both parents and 4 grandparents who are Japanese. This includes healthy second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
- •For the Part A3, participants should be Chinese defined as having both parents and 4 grandparents who are ethnically Chinese. This includes second and third generation Chinese whose parents or grandparents are living in a country other than China.
排除标准
- •History of any clinically important disease or disorder.
- •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 study intervention.
- •Any clinically important abnormalities in laboratory values, clinical chemistry, hematology, urinalysis results, or vital signs.
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs of a similar class to AZD
- •Has received prescription, non-prescription, or experimental medications for weight loss within 3 months prior to the Screening Visit.
- •History of psychosis or bipolar disorder or major depressive disorder within the past 2 years with the participant being clinically unstable.
研究组 & 干预措施
Part A3 (Chinese SAD): Cohort 1 - AZD1043 (Dose Z)
Chinese participants will receive a single dose of AZD1043 or placebo.
干预措施: Placebo (Other)
Part B1 (Global MAD): Cohort 1 - AZD1043 (Dose A)
Participants will receive multiple doses of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part B1 (Global MAD): Cohort 1 - AZD1043 (Dose A)
Participants will receive multiple doses of AZD1043 or placebo.
干预措施: Placebo (Other)
Part A1 (Global SAD): Cohort 3 - AZD1043 (Dose 3)
Participants will receive a single dose of AZD1043 (Dose 3) or placebo.
干预措施: AZD1043 (Drug)
Part A1 (Global SAD): Cohort 4 - AZD1043 (Dose 4)
Participants will receive a single dose of AZD1043 (Dose 4) or placebo.
干预措施: AZD1043 (Drug)
Part B2 (Japanese MAD): Cohort 1 - AZD1043 (Dose D)
Japanese participants will receive multiple doses of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part B2 (Japanese MAD): Cohort 1 - AZD1043 (Dose D)
Japanese participants will receive multiple doses of AZD1043 or placebo.
干预措施: Placebo (Other)
Part A1 (Global SAD): Cohort 3 - AZD1043 (Dose 3)
Participants will receive a single dose of AZD1043 (Dose 3) or placebo.
干预措施: Placebo (Other)
Part B1 (Global MAD): Cohort 2 - AZD1043 (Dose B)
Participants will receive multiple doses of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part B1 (Global MAD): Cohort 2 - AZD1043 (Dose B)
Participants will receive multiple doses of AZD1043 or placebo.
干预措施: Placebo (Other)
Part B1 (Global MAD): Cohort 3 - AZD1043 (Dose C)
Participants will receive multiple doses of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part B1 (Global MAD): Cohort 3 - AZD1043 (Dose C)
Participants will receive multiple doses of AZD1043 or placebo.
干预措施: Placebo (Other)
Part A1 (Global SAD): Cohort 1 - AZD1043 (Dose 1)
Participants will receive a single dose of AZD1043 (Dose 1) or placebo.
干预措施: AZD1043 (Drug)
Part A1 (Global SAD): Cohort 2 - AZD1043 (Dose 2)
Participants will receive a single dose of AZD1043 (Dose 2) or placebo.
干预措施: AZD1043 (Drug)
Part A1 (Global SAD): Cohort 2 - AZD1043 (Dose 2)
Participants will receive a single dose of AZD1043 (Dose 2) or placebo.
干预措施: Placebo (Other)
Part A2 (Japanese SAD): Cohort 1 - AZD1043 (Dose X)
Japanese participants will receive a single dose of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part A2 (Japanese SAD): Cohort 1 - AZD1043 (Dose X)
Japanese participants will receive a single dose of AZD1043 or placebo.
干预措施: Placebo (Other)
Part A2 (Japanese SAD): Cohort 2 - AZD1043 (Dose Y)
Japanese participants will receive a single dose of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part A2 (Japanese SAD): Cohort 2 - AZD1043 (Dose Y)
Japanese participants will receive a single dose of AZD1043 or placebo.
干预措施: Placebo (Other)
Part A3 (Chinese SAD): Cohort 1 - AZD1043 (Dose Z)
Chinese participants will receive a single dose of AZD1043 or placebo.
干预措施: AZD1043 (Drug)
Part A1 (Global SAD): Cohort 1 - AZD1043 (Dose 1)
Participants will receive a single dose of AZD1043 (Dose 1) or placebo.
干预措施: Placebo (Other)
Part A1 (Global SAD): Cohort 4 - AZD1043 (Dose 4)
Participants will receive a single dose of AZD1043 (Dose 4) or placebo.
干预措施: Placebo (Other)
Part A1 (Global SAD): Cohort 5 - AZD1043 (Dose 5)
Participants will receive a single dose of AZD1043 (Dose 5) or placebo.
干预措施: AZD1043 (Drug)
Part A1 (Global SAD): Cohort 5 - AZD1043 (Dose 5)
Participants will receive a single dose of AZD1043 (Dose 5) or placebo.
干预措施: Placebo (Other)
Part A1 (Global SAD): Cohort 6 - AZD1043 (Dose 6)
Participants will receive a single dose of AZD1043 (Dose 6) or placebo.
干预措施: AZD1043 (Drug)
Part A1 (Global SAD): Cohort 6 - AZD1043 (Dose 6)
Participants will receive a single dose of AZD1043 (Dose 6) or placebo.
干预措施: Placebo (Other)
结局指标
主要结局
Number of participants with adverse events (AEs), serious adverse events (SAEs), AE leading to discontinuation (DAEs), and AEs of special interest (AESIs)
时间窗: Part A (SAD): From Day-35 to Day 253; Part B (MAD): From Day 1 to Day 253
To assess the safety and tolerability of a single or multiple doses of AZD1043 in healthy adult participants living with overweight and/or obesity, including participants of Japanese and Chinese descent.
次要结局
- Area under concentration-time curve from time 0 to infinity (AUCinf) (Part A only)(From Day 1 to Day 253)
- Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)(From Day 1 to Day 253)
- Maximum observed drug concentration (Cmax)(From Day 1 to Day 253)