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
Overview
- Phase
- Phase 1
- Intervention
- AZD6793
- Conditions
- Healthy Participants
- Sponsor
- AstraZeneca
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Part 2 (MAD): Number of Participants with Adverse Events
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
The main purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of oral AZD6793 in healthy Japanese and Chinese participants.
Detailed Description
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. Participants will be randomized to receive AZD6793 and placebo in both Part 1 and Part 2. Participants who enrolled in Part 1 will be excluded from participation in Part 2 of the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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,
Exclusion Criteria
- •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).
Arms & Interventions
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.
Intervention: AZD6793
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.
Intervention: Placebo
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.
Intervention: AZD6793
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.
Intervention: Placebo
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.
Intervention: AZD6793
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.
Intervention: Placebo
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.
Intervention: AZD6793
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.
Intervention: Placebo
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.
Intervention: AZD6793
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Part 2 (MAD): Number of Participants with Adverse Events
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)