Healthy Participants
Conditions
Keywords
Liver disease, Single ascending dose, Multiple ascending dose
Brief summary
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.
Detailed description
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.
Interventions
DRUGAZD2389
Participants will receive AZD2389 orally as a single ascending dose or multiple ascending dose.
DRUGPlacebo
Participants will receive placebo matching the AZD2389 dose orally as a single ascending dose or multiple ascending dose.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A (SAD): Number of participants with adverse events (AE) and serious adverse events (SAE) | Day ≤ -28 (Only SAE), Day -1 (Only SAE), Days 1 and 2, Day 8 Post-dose (± 1 day) | To assess the safety and tolerability of AZD2389 following oral administration of single ascending doses in healthy participants, including Japanese and Chinese participants. |
| Part B (MAD): Number of participants with AE and SAE | Day ≤ -28 (Only SAE), Day -1 (Only SAE), Days 1 to 12, Day 17 (± 1 day) | To assess the safety and tolerability of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A (SAD): Terminal rate constant (λz) | Day 1 and Day 2 | To characterize the λz of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] | Day 1 and Day 2 | To characterize the Ae(t1-t2) of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Area under plasma concentration time curve from zero to infinity (AUCinf) | Day 1 and Day 2 | To characterize the AUCinf of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Dose normalized AUCinf (AUCinf/D) | Day 1 and Day 2 | To characterize the AUCinf/D of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) | Day 1 and Day 2 | To characterize the AUClast of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Dose normalized AUClast (AUClast/D) | Day 1 and Day 2 | To characterize the AUClast/D of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Apparent total body clearance of drug (CL/F) | Day 1 and Day 2 | To characterize the CL/F of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Maximum observed plasma (peak) drug concentration (Cmax) | Day 1 and Day 2 | To characterize the Cmax of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Dose normalized Cmax (Cmax/D) | Day 1 and Day 2 | To characterize the Cmax/D of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Renal clearance (CLR) | Day 1 and Day 2 | To characterize the CLR of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)] | Day 1 and Day 2 | To characterize the fe(t1-t2) of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Mean residence time (MRTinf) | Day 1 and Day 2 | To characterize the MRTinf of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Apparent terminal elimination half-life (t½λz) | Day 1 and Day 2 | To characterize the t½λz of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Time of last quantifiable concentration (tlast) | Day 1 and Day 2 | To characterize the tlast of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Time to reach peak or maximum observed concentration (tmax) | Day 1 and Day 2 | To characterize the tmax of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Apparent volume of distribution based on the terminal phase (Vz/F) | Day 1 and Day 2 | To characterize the Vz/F of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part A (SAD): Change in PD biomarkers over time | Day 1 and Day 2 | 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. |
| Part B (MAD): Plasma concentrations of AZD2389 | Day 1 to Day 12 | To characterize the plasma concentration of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Urine concentrations of AZD2389 | Day 1 and Days 10 to 12 | To characterize the urine concentration of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Terminal rate constant (λz) | Day 1 to Day 12 | To characterize the λz of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] | Day 1 and Days 10 to 12 | To characterize the Ae(t1-t2) of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Area under concentration curve from time 0 to the last quantifiable concentration (AUClast) | Day 1 to Day 12 | To characterize the AUClast of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Area under the concentration-time curve in the dose interval (AUCtau) | Day 1 to Day 12 | To characterize the AUCtau of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Dose normalized AUCtau (AUCtau/D) | Day 1 to Day 12 | To characterize the AUCtau/D of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Dose normalized AUClast (AUClast/D) | Day 1 to Day 12 | To characterize the AUClast/D of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Apparent total body clearance of drug (CL/F) | Day 1 and Days 10 to 12 | To characterize the CL/F of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Renal clearance (CLR) | Day 1 and Days 10 to 12 | To characterize the CLR of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Maximum observed plasma (peak) drug concentration (Cmax) | Day 1 to Day 12 | To characterize the Cmax of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Dose normalized Cmax (Cmax/D) | Day 1 to Day 12 | To characterize the Cmax/D of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Observed lowest concentration before the next dose is administered(Ctrough) | Day 1 to Day 12 | To characterize the Ctrough of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)] | Day 1 and Days 10 to 12 | To characterize the fe(t1-t2) of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Accumulation ratio for AUC (Rac AUC) | Day 1 to Day 12 | To characterize the Rac AUC of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Accumulation ratio for Cmax (Rac Cmax) | Day 1 to Day 12 | To characterize the Rac Cmax of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part A (SAD): Plasma concentrations of AZD2389 | Day 1 and Day 2 | To characterize the plasma concentration of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
| Part B (MAD): Apparent terminal elimination half-life (t½λz) | Day 1 to Day 12 | To characterize the t½λz of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Apparent volume of distribution based on the terminal phase (Vz/F) | Day 1 to Day 12 | To characterize the Vz/F of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part B (MAD): Change in PD biomarkers over time | Days 1, 2, 4, 8, and 10 | 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. |
| Part B (MAD): Time to reach peak or maximum observed concentration (tmax) | Day 1 to Day 12 | To characterize the tmax of AZD2389 following oral administration of multiple ascending doses in healthy participants, including Japanese participants. |
| Part A (SAD): Urine concentrations of AZD2389 | Day 1 and Day 2 | To characterize the urine concentration of AZD2389 after single oral dosing in healthy participants, including Japanese and Chinese participants. |
Countries
United States
Outcome results
None listed