Clinical trial NCT06138795: A Single and Multiple Ascending Dose Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD2389 in Healthy Participants
Official title: A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD2389 After Single and Multiple Ascending Doses to Healthy Participants.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Liver disease
Single ascending dose
Multiple ascending dose
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Placebo-controlled
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A (SAD): Number of participants with adverse events (AE) and serious adverse events (SAE)
timeFrame: Day ≤ -28 (Only SAE), Day -1 (Only SAE), Days 1 and 2, Day 8 Post-dose (± 1 day)
measure: Part B (MAD): Number of participants with AE and SAE
timeFrame: Day ≤ -28 (Only SAE), Day -1 (Only SAE), Days 1 to 12, Day 17 (± 1 day)
Secondary outcomes:
measure: Part A (SAD): Plasma concentrations of AZD2389
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Urine concentrations of AZD2389
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Terminal rate constant (λz)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Area under plasma concentration time curve from zero to infinity (AUCinf)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Dose normalized AUCinf (AUCinf/D)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Dose normalized AUClast (AUClast/D)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Apparent total body clearance of drug (CL/F)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Maximum observed plasma (peak) drug concentration (Cmax)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Dose normalized Cmax (Cmax/D)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Renal clearance (CLR)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Mean residence time (MRTinf)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Apparent terminal elimination half-life (t½λz)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Time of last quantifiable concentration (tlast)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Time to reach peak or maximum observed concentration (tmax)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: Day 1 and Day 2
measure: Part A (SAD): Change in PD biomarkers over time
timeFrame: Day 1 and Day 2
measure: Part B (MAD): Plasma concentrations of AZD2389
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Urine concentrations of AZD2389
timeFrame: Day 1 and Days 10 to 12
measure: Part B (MAD): Terminal rate constant (λz)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]
timeFrame: Day 1 and Days 10 to 12
measure: Part B (MAD): Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Area under the concentration-time curve in the dose interval (AUCtau)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Dose normalized AUCtau (AUCtau/D)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Dose normalized AUClast (AUClast/D)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Apparent total body clearance of drug (CL/F)
timeFrame: Day 1 and Days 10 to 12
measure: Part B (MAD): Renal clearance (CLR)
timeFrame: Day 1 and Days 10 to 12
measure: Part B (MAD): Maximum observed plasma (peak) drug concentration (Cmax)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Dose normalized Cmax (Cmax/D)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Observed lowest concentration before the next dose is administered(Ctrough)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]
timeFrame: Day 1 and Days 10 to 12
measure: Part B (MAD): Accumulation ratio for AUC (Rac AUC)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Accumulation ratio for Cmax (Rac Cmax)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Time to reach peak or maximum observed concentration (tmax)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Apparent terminal elimination half-life (t½λz)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: Day 1 to Day 12
measure: Part B (MAD): Change in PD biomarkers over time
timeFrame: Days 1, 2, 4, 8, and 10
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
References: