A Single-blind, Randomized, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of an Oral Suspension of AZD6793 Following Single and Multiple Doses in Japanese and Chinese Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Part 2 (MAD): Number of Participants with Adverse Events
研究概览
简要总结
The main purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of oral AZD6793 in healthy Japanese and Chinese participants.
详细描述
This study will be conducted to assess the safety, tolerability, and PK of oral AZD6793 suspension following single (Part 1) and multiple (Part 2) administrations in healthy Japanese and Chinese participants performed at a single Clinical Unit.
Part 1 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2).
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 until at least 72 hours after study intervention administration.
- A Follow-up Visit within 6 ± 1 days after the study intervention administration.
Part 2 of the study will comprise:
- A Screening Period of maximum 28 days (Day -29 to Day -2).
- A Treatment Period during which participants will be resident at the Clinical Unit from Day -1 (the day before first study intervention administration [Day 1]) until Day 10.
- A Follow-up Visit within 6 ± 1 days after the last study intervention administration.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •For Japanese participants only:
- •Participant was born in Japan
- •Participant has 2 Japanese biological parents and 4 Japanese grandparents as confirmed by the interview.
- •Participant did not live outside of Japan for more than 10 years at the time of the Screening Visit.
- •For Chinese participants only:
- •Participant was born in China (including Hong Kong, Macau, and Taiwan)
- •Participant has 2 Chinese biological parents and 4 Chinese grandparents as confirmed by the interview.
- •Participant did not live outside of greater China for more than 10 years at the time of the Screening Visit.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- •Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception,
- •Have a body mass index between 18 and 30 kilograms per meter square (kg/m2) inclusive and weigh at least 45 kilograms (kg), at the Screening Visit.
- •Females of non-childbearing potential must be confirmed at the screening Visit by fulfilling one of the following criteria:
- •Postmenopausal defined as amenorrhea for at least 12 months 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).
排除标准
- •1. History of any clinically important disease or disorder or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •3. Diagnosis or history of immunodeficiency or increased susceptibility to severe infection, or a clinically significant infection within 4 weeks of the Screening Visit.
- •4. Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus.
- •5. 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
- •6. Plasma donation within one month of the Screening Visit or any blood donation/blood loss greater than (>) 500 milliliter (mL) during the 3 months prior to the Screening Visit.
- •7. Participants who have previously received AZD
- •Positive or indeterminate QuantiFERON® TB test at Screening Visit.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months prior to the Screening Visit.
- •10. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the Investigator.
- •11. Positive screen for drugs of abuse, or alcohol or cotinine at the Screening Visit or admission to the Clinical Unit (Day -1).
- •12. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) defined as the regular consumption of more than 500 mg of caffeine per day (eg, > 5 cups of coffee [one cup ~100 mg caffeine]; one cup of tea ~30 mg caffeine).
- •13. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of study intervention.
研究组 & 干预措施
Part 1: Cohort 1 AZD6793
6 Healthy Japanese participants will receive single dose of AZD6793 dose 1 and 2 healthy Japanese participants will receive matching placebo to AZD6793 as oral suspension on Day 1.
干预措施: AZD6793 (Drug)
Part 1: Cohort 1 AZD6793
6 Healthy Japanese participants will receive single dose of AZD6793 dose 1 and 2 healthy Japanese participants will receive matching placebo to AZD6793 as oral suspension on Day 1.
干预措施: Placebo (Drug)
Part 1: Cohort 2 AZD6793
6 Healthy Japanese participants will receive single dose of AZD6793 dose 2 and 2 healthy Japanese participants will receive matching placebo to AZD6793 as oral suspension on Day 1.
干预措施: AZD6793 (Drug)
Part 1: Cohort 2 AZD6793
6 Healthy Japanese participants will receive single dose of AZD6793 dose 2 and 2 healthy Japanese participants will receive matching placebo to AZD6793 as oral suspension on Day 1.
干预措施: Placebo (Drug)
Part 1: Cohort 3 AZD6793
6 Healthy Chinese participants will receive single dose of AZD6793 dose 1 and 2 healthy Chinese participants will receive matching placebo to AZD6793 as oral suspension on Day 1.
干预措施: AZD6793 (Drug)
Part 1: Cohort 3 AZD6793
6 Healthy Chinese participants will receive single dose of AZD6793 dose 1 and 2 healthy Chinese participants will receive matching placebo to AZD6793 as oral suspension on Day 1.
干预措施: Placebo (Drug)
Part 2: Cohort 1 AZD6793
6 Japanese participants will receive single dose of AZD6793 and 2 participants will receive matching placebo on Day 1. After a washout of at least 48 hours, participants will receive AZD6793 or placebo once daily from Day 3 to Day 8.
干预措施: AZD6793 (Drug)
Part 2: Cohort 1 AZD6793
6 Japanese participants will receive single dose of AZD6793 and 2 participants will receive matching placebo on Day 1. After a washout of at least 48 hours, participants will receive AZD6793 or placebo once daily from Day 3 to Day 8.
干预措施: Placebo (Drug)
Part 2: Cohort 2 AZD6793
6 Chinese participants will receive single dose of AZD6793 and 2 participants will receive matching placebo on Day 1. After a washout of at least 48 hours, participants will receive AZD6793 or placebo once daily from Day 3 to Day 8.
干预措施: AZD6793 (Drug)
Part 2: Cohort 2 AZD6793
6 Chinese participants will receive single dose of AZD6793 and 2 participants will receive matching placebo on Day 1. After a washout of at least 48 hours, participants will receive AZD6793 or placebo once daily from Day 3 to Day 8.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 2 (MAD): Number of Participants with Adverse Events
时间窗: From Day 1 up to Follow up visit (Day 14±1)
To assess the safety and tolerability of AZD6793 following oral administration of multiple doses in healthy Japanese and Chinese participants.
Part 1 (SAD): Number of Participants with Adverse Events
时间窗: From Day 1 up to Follow up visit (Day 7±1)
To assess the safety and tolerability of AZD6793 following oral administration of single ascending doses in healthy Japanese participants and a single dose in healthy Chinese participants.
次要结局
- Part 1 (SAD): Apparent Total Body Clearance of Drug from Plasma After Extravascular Administration (CL/F)(Day 1 to Day 3)
- Part 2 (MAD) : Concentration at the End of The Dosing Interval (Ctrough)(Day 1 to Day 10)
- Part 1 (SAD): Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vz/F)(Day 1 to Day 3)
- Part 1 (SAD): Terminal Rate Constant, Estimated by Log-Linear Least Squares Regression of the Terminal Part of The Concentration-Time Curve (λz)(Day 1 to Day 3)
- Part 1 (SAD): Partial Area Under the Plasma Concentration Time Curve from Time Zero to Time 24 (AUC[0-24])(Day 1 to Day 3)
- Part 1 (SAD): Area Under the Plasma Concentration Curve from Time Zero to the Last Quantifiable Concentration (AUClast)(Day 1 to Day 3)
- Part 1 (SAD): Area Under the Plasma Concentration Time Curve from Time Zero to Infinity (AUCinf)(Day 1 to Day 3)
- Part 1 (SAD): Dose Normalized AUCinf(Day 1 to Day 3)
- Part 2 (MAD): Maximum Observed Plasma Drug Concentration (Cmax)(Day 1 to Day 10)
- Part 2 (MAD): Dose Normalized Cmax(Day 1 to Day 10)
- Part 2 (MAD): Ratio of the Area Under the Curve (Rac AUC)(Day 1 to Day 10)
- Part 2 (MAD): Accumulation Ratio Based on Cmax (Rac Cmax)(Day 1 to Day 10)
- Part 1 (SAD): Partial Area Under the Plasma Concentration Time Curve from Time Zero to Time 12 (AUC[0-12])(Day 1 to Day 3)
- Part 1 (SAD) : Maximum Observed Plasma Drug Concentration(Day 1 to Day 3)
- Part 1 (SAD): Time to Reach Peak Concentration (tmax)(Day 1 to Day 3)
- Part 1 (SAD): Half-life Associated with Terminal Slope of a Semi-Logarithmic Concentration-Time Curve (t1/2λz)(Day 1 to Day 3)
- Part 1 (SAD): Dose Normalized AUClast(Day 1 to Day 3)
- Part 1 (SAD): Dose Normalized Cmax(Day 1 to Day 3)
- Part 2 (MAD): Half-life Associated with Terminal Slope of a Semi-Logarithmic Concentration-Time Curve (t1/2λz)(Day 1 to Day 10)
- Part 2 (MAD): Partial Area Under the Plasma Concentration Time Curve from Time Zero to Time 24 (AUC[0-24])(Day 1 to Day 10)
- Part 2 (MAD): Temporal Change Parameter (TCP)(Day 1 to Day 10)
- Part 2 (MAD): Time to Reach Peak Concentration (tmax)(Day 1 to Day 10)
- Part 2 (MAD): Terminal Rate Constant, Estimated by Log-Linear Least Squares Regression of the Terminal Part of The Concentration-Time Curve (λz)(Day 1 to Day 10)
- Part 2 (MAD): Area Under the Plasma Concentration Curve from Time Zero to the Last Quantifiable Concentration (AUClast)(Day 1 to Day 10)
- Part 2 (MAD): Area Under the Plasma Concentration Time Curve from Time Zero to Infinity (AUCinf)(Day 1 to Day 10)
- Part 2 (MAD): Area Under Plasma Concentration-Time Curve in The Dosing Interval Tau (AUCtau)(Day 1 to Day 10)
- Part 2 (MAD): Apparent Total Body Clearance of Drug from Plasma After Extravascular Administration (CL/F)(Day 1 to Day 10)
- Part 2 (MAD): Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vz/F)(Day 1 to Day 10)
- Part 2 (MAD): Dose Normalized AUClast(Day 1 to Day 10)
- Part 2 (MAD): Dose Normalized AUCtau(Day 1 to Day 10)
- Part 2 (MAD): Cumulative Amount of Unchanged Drug Excreted into Urine (Aeinf)(Days 1, 2, and 8)
- Part 2 (MAD): Amount of Unchanged Drug Excreted into Urine from Time t1 to Time t2 (Ae[t1-t2])(Days 1, 2, and 8)
- Part 2 (MAD): Renal Clearance (CLR)(Days 1, 2, and 8)