Clinical trial NCT06368440: A Study to Investigate the Safety and Pharmacokinetics of AZD6793 in Healthy Japanese and Chinese Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Chronic obstructive pulmonary disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-04-16
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Eligibility criteria: Main Inclusion Criteria:

1. For Japanese participants only:

   1. Participant was born in Japan
   2. Participant has 2 Japanese biological parents and 4 Japanese grandparents as confirmed by the interview.
   3. Participant did not live outside of Japan for more than 10 years at the time of the Screening Visit.
2. For Chinese participants only:

   1. Participant was born in China (including Hong Kong, Macau, and Taiwan)
   2. Participant has 2 Chinese biological parents and 4 Chinese grandparents as confirmed by the interview.
   3. Participant did not live outside of greater China for more than 10 years at the time of the Screening Visit.
3. All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
4. Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception,
5. 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.
6. Females of non-childbearing potential must be confirmed at the screening Visit by fulfilling one of the following criteria:

   1. Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
   2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (but not tubal ligation).

Main 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 AZD6793.

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 AZD6793. 8. Positive or indeterminate QuantiFERON® TB test at Screening Visit. 9. 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.

Primary outcomes:
measure: Part 1 (SAD): Number of Participants with Adverse Events
timeFrame: From Day 1 up to Follow up visit (Day 7±1)
measure: Part 2 (MAD): Number of Participants with Adverse Events
timeFrame: From Day 1 up to Follow up visit (Day 14±1)
Secondary outcomes:
measure: Part 1 (SAD) : Maximum Observed Plasma Drug Concentration
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Time to Reach Peak Concentration (tmax)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Terminal Rate Constant, Estimated by Log-Linear Least Squares Regression of the Terminal Part of The Concentration-Time Curve (λz)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Half-life Associated with Terminal Slope of a Semi-Logarithmic Concentration-Time Curve (t1/2λz)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Partial Area Under the Plasma Concentration Time Curve from Time Zero to Time 12 (AUC[0-12])
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Partial Area Under the Plasma Concentration Time Curve from Time Zero to Time 24 (AUC[0-24])
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Area Under the Plasma Concentration Curve from Time Zero to the Last Quantifiable Concentration (AUClast)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Area Under the Plasma Concentration Time Curve from Time Zero to Infinity (AUCinf)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Apparent Total Body Clearance of Drug from Plasma After Extravascular Administration (CL/F)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vz/F)
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Dose Normalized AUClast
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Dose Normalized AUCinf
timeFrame: Day 1 to Day 3
measure: Part 1 (SAD): Dose Normalized Cmax
timeFrame: Day 1 to Day 3
measure: Part 2 (MAD): Maximum Observed Plasma Drug Concentration (Cmax)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD) : Concentration at the End of The Dosing Interval (Ctrough)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Temporal Change Parameter (TCP)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Time to Reach Peak Concentration (tmax)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Terminal Rate Constant, Estimated by Log-Linear Least Squares Regression of the Terminal Part of The Concentration-Time Curve (λz)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Half-life Associated with Terminal Slope of a Semi-Logarithmic Concentration-Time Curve (t1/2λz)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Partial Area Under the Plasma Concentration Time Curve from Time Zero to Time 24 (AUC[0-24])
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Area Under the Plasma Concentration Curve from Time Zero to the Last Quantifiable Concentration (AUClast)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Area Under the Plasma Concentration Time Curve from Time Zero to Infinity (AUCinf)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Area Under Plasma Concentration-Time Curve in The Dosing Interval Tau (AUCtau)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Apparent Total Body Clearance of Drug from Plasma After Extravascular Administration (CL/F)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Vz/F)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Dose Normalized AUClast
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Dose Normalized AUCtau
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Dose Normalized Cmax
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Ratio of the Area Under the Curve (Rac AUC)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Accumulation Ratio Based on Cmax (Rac Cmax)
timeFrame: Day 1 to Day 10
measure: Part 2 (MAD): Amount of Unchanged Drug Excreted into Urine from Time t1 to Time t2 (Ae[t1-t2])
timeFrame: Days 1, 2, and 8
measure: Part 2 (MAD): Cumulative Amount of Unchanged Drug Excreted into Urine (Aeinf)
timeFrame: Days 1, 2, and 8
measure: Part 2 (MAD): Renal Clearance (CLR)
timeFrame: Days 1, 2, and 8
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
References: