Clinical trial NCT06974565: A Study to Investigate the Pharmacokinetics of AZD2389 in Healthy Participants When Administered Alone and in Combination With Quinidine
Official title: An Open-label, Randomized, Cross-over, Single Dose Study in Healthy Participants to Assess the Pharmacokinetics of AZD2389 When Administered Alone and in Combination With Quinidine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Chronic Liver Disease
Healthy Participants
Keywords: Hepatic Fibrosis
Fibroblast Activation Protein Inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-05-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the pharmacokinetics (PK) and safety of AZD2389 when administered alone and in combination with quinidine in healthy participants.

Detailed description: This is a 2-way cross-over study to evaluate the effect of quinidine on the PK of AZD2389.

The study will include 2 Treatments - Treatment A - AZD2389 Treatment B - AZD2389 + quinidine

The study will comprise -

1. A Screening Period of maximum 28 days.
2. Period 1: single dose administration of Treatment A or Treatment B on Day 1. Period 2 will start after a washout period of at least 7 days.
3. Period 2: single dose of alternate treatment on Day 8.
4. A Follow-up Visit: participants will return for a Follow-up Visit, 7 to 14 days after the last AZD2389 PK sample in Period 2.

Participants will be randomized to one of the 2 treatment sequences -

1. Sequence AB: Treatment A in Period 1, Treatment B in Period 2.
2. Sequence BA: Treatment B in Period 1, Treatment A in Period 2.

Eligibility criteria: Inclusion Criteria:

* Healthy male and female (of non-childbearing potential) participants with suitable veins for cannulation or repeated venipuncture.
* All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
* Females of non-childbearing potential must be confirmed at the Screening Visit.
* Sexually active fertile male participants with partners of childbearing potential must adhere to the study specific contraception methods from the time of first administration of study intervention administration until 3 months after the study Follow-up Visit.
* Have a body mass index between 18 and 32 kg/m2, inclusive, and weigh at least 50 kg at the Screening Visit.

Exclusion Criteria:

* History of any clinically important disease or disorder.
* History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* Any clinically important abnormalities in hematology, clinical chemistry, urinalysis, coagulation results or other laboratory values and vital signs.
* Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV).
* Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead electrocardiogram (ECG) at Screening.
* Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
* Current smokers or those who have smoked or used nicotine products within the previous 3 months prior to screening.
* Positive screen for drugs of abuse, or alcohol or cotinine at Screening.
* History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
* History of hypersensitivity to dipeptidyl peptidase 4 (DPP4) inhibitors.

Primary outcomes:
measure: Ratio of Test treatment (AZD2389 + quinidine) to Reference treatment (AZD2389) based on maximum observed plasma concentration (RCmax)
timeFrame: Day 1 to Day 10
measure: Ratio of Test treatment (AZD2389 + quinidine) to Reference treatment (AZD2389) based on area under concentration-time curve from time 0 to infinity (RAUCinf)
timeFrame: Day 1 to Day 10
measure: Ratio of Test treatment (AZD2389 + quinidine) to Reference treatment (AZD2389) based on area under concentration-time curve from time 0 to the last quantifiable concentration (RAUClast)
timeFrame: Day 1 to Day 10
Secondary outcomes:
measure: Apparent total body clearance (CL/F) of AZD2389
timeFrame: Day 1 to Day 10
measure: Volume of distribution (apparent) following extravascular administration (based on terminal phase) (Vz/F) of AZD2389
timeFrame: Day 1 to Day 10
measure: Terminal elimination half-life (t1/2λz) of AZD2389
timeFrame: Day 1 to Day 10
measure: Time to reach maximum observed concentration (tmax) of AZD2389
timeFrame: Day 1 to Day 10
measure: Maximum observed plasma concentration (Cmax) of AZD2389
timeFrame: Day 1 to Day 10
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of AZD2389
timeFrame: Day 1 to Day 10
measure: Area under concentration-time curve from time zero to infinity (AUCinf) of AZD2389
timeFrame: Day 1 to Day 10
measure: Renal Clearance (CLR) of AZD2389 from plasma
timeFrame: Day 1 to Day 10
measure: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe[t1-t2]) of AZD2389
timeFrame: Day 1 to Day 10
measure: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 (Ae[t1-t2]) of AZD2389
timeFrame: Day 1 to Day 10
measure: Percent change from baseline in fibroblast activation protein (FAP) inhibition
timeFrame: Baseline, Day 1 to Day 10
measure: Number of participants with Adverse Events (AEs)
timeFrame: From Screening (Day -28 to Day -2) to Follow-up visit (upto 8 weeks)
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: