A Single and Multiple Ascending Dose Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD2389 in Healthy Participants

AstraZeneca120 enrolled

Overview

This study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD2389 following single and multiple dose administration (SAD/MAD) to healthy participants.

This is a Phase I, First In Human (FIH), randomized, single-blind, placebo-controlled, single and multiple ascending dose study in healthy male and/or female participants of non-childbearing potential including healthy participants of Chinese and Japanese ethnicity performed at a single center. The study consists of 2 parts: Part A and Part B. Part A has been planned to be conducted with 78 participants and Part B has been planned to be conducted with 32 participants. Each participant in Part A and Part B will be involved in the study for up to 8 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

120

Conditions

Healthy Participants

Interventions

AZD2389DRUG

Participants will receive AZD2389 orally as a single ascending dose or multiple ascending dose.

PlaceboDRUG

Participants will receive placebo matching the AZD2389 dose orally as a single ascending dose or multiple ascending dose.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy male and female (of non-childbearing potential) participants with suitable veins for cannulation or repeated venipuncture. * For the healthy Japanese cohorts (Parts A2 and B2): healthy participants are to be Japanese (e.g., natives of Japan or Japanese Americans), defined as 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 healthy Chinese cohort (Part A3): healthy participants are to 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. Exclusion Criteria: * Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP. * Known or suspected history of alcohol or drug abuse and smokers. * Plasma donation within one month of the Screening Visit or any blood donation/blood loss \> 500 mL during the 3 months prior to the Screening Visit. * History of coagulation or bleeding disorders or use of anti-platelets/anti-coagulants during the 3 months prior to the Screening Visit, as judged by the investigator. * History of hypersensitivity as judged by the investigator, to drugs with a similar chemical structure or class. * History of severe dermatological disorders, eg, bullous pemphigoid or Stevens-Johnson syndrome, or clinically significant new or healing wounds in areas of the body not always covered by clothing such as face, forearm, and lower leg, as judged by the investigator.

Locations (1)

Research Site

Glendale, California, United States

Outcomes

Primary Outcomes

Part A (SAD): Number of participants with adverse events (AE) and serious adverse events (SAE)

To assess the safety and tolerability of AZD2389 following oral administration of single ascending doses in healthy participants, including Japanese and Chinese participants.

Time frame: Day ≤ -28 (Only SAE), Day -1 (Only SAE), Days 1 and 2, Day 8 Post-dose (± 1 day)

Part B (MAD): Number of participants with AE and SAE

To assess the safety and tolerability of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day ≤ -28 (Only SAE), Day -1 (Only SAE), Days 1 to 12, Day 17 (± 1 day)

Secondary Outcomes

Part A (SAD): Plasma concentrations of AZD2389

To characterize the plasma concentration of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Urine concentrations of AZD2389

To characterize the urine concentration of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Terminal rate constant (λz)

To characterize the λz of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]

To characterize the Ae(t1-t2) of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Data from ClinicalTrials.gov

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Time frame: Day 1 and Day 2

Part A (SAD): Area under plasma concentration time curve from zero to infinity (AUCinf)

To characterize the AUCinf of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Dose normalized AUCinf (AUCinf/D)

To characterize the AUCinf/D of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)

To characterize the AUClast of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Dose normalized AUClast (AUClast/D)

To characterize the AUClast/D of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Apparent total body clearance of drug (CL/F)

To characterize the CL/F of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Maximum observed plasma (peak) drug concentration (Cmax)

To characterize the Cmax of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Dose normalized Cmax (Cmax/D)

To characterize the Cmax/D of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Renal clearance (CLR)

To characterize the CLR of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]

To characterize the fe(t1-t2) of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Mean residence time (MRTinf)

To characterize the MRTinf of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Apparent terminal elimination half-life (t½λz)

To characterize the t½λz of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Time of last quantifiable concentration (tlast)

To characterize the tlast of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Time to reach peak or maximum observed concentration (tmax)

To characterize the tmax of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Apparent volume of distribution based on the terminal phase (Vz/F)

To characterize the Vz/F of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part A (SAD): Change in PD biomarkers over time

To characterize the percentage change in PD biomarkers over time compared to baseline of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants.

Time frame: Day 1 and Day 2

Part B (MAD): Plasma concentrations of AZD2389

To characterize the plasma concentration of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Urine concentrations of AZD2389

To characterize the urine concentration of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 and Days 10 to 12

Part B (MAD): Terminal rate constant (λz)

To characterize the λz of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]

To characterize the Ae(t1-t2) of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 and Days 10 to 12

Part B (MAD): Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)

To characterize the AUClast of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Area under the concentration-time curve in the dose interval (AUCtau)

To characterize the AUCtau of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Dose normalized AUCtau (AUCtau/D)

To characterize the AUCtau/D of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Dose normalized AUClast (AUClast/D)

To characterize the AUClast/D of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Apparent total body clearance of drug (CL/F)

To characterize the CL/F of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 and Days 10 to 12

Part B (MAD): Renal clearance (CLR)

To characterize the CLR of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 and Days 10 to 12

Part B (MAD): Maximum observed plasma (peak) drug concentration (Cmax)

To characterize the Cmax of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Dose normalized Cmax (Cmax/D)

To characterize the Cmax/D of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Observed lowest concentration before the next dose is administered(Ctrough)

To characterize the Ctrough of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]

To characterize the fe(t1-t2) of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 and Days 10 to 12

Part B (MAD): Accumulation ratio for AUC (Rac AUC)

To characterize the Rac AUC of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Accumulation ratio for Cmax (Rac Cmax)

To characterize the Rac Cmax of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Time to reach peak or maximum observed concentration (tmax)

To characterize the tmax of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Apparent terminal elimination half-life (t½λz)

To characterize the t½λz of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Apparent volume of distribution based on the terminal phase (Vz/F)

To characterize the Vz/F of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Day 1 to Day 12

Part B (MAD): Change in PD biomarkers over time

To characterize the percentage change in PD biomarkers over time compared to baseline of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants.

Time frame: Days 1, 2, 4, 8, and 10