A Study to Investigate the Pharmacokinetics of AZD2389 in Healthy Participants When Administered Alone and in Combination With Quinidine
- Conditions
- Advanced Chronic Liver DiseaseHealthy Participants
- Interventions
- Registration Number
- NCT06974565
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Sequence AB AZD2389 Participants will receive a single dose of Treatment A (AZD2389) in Period 1 and a single dose of Treatment B (AZD2389 + quinidine) in Period 2. Sequence AB Quinidine Participants will receive a single dose of Treatment A (AZD2389) in Period 1 and a single dose of Treatment B (AZD2389 + quinidine) in Period 2. Sequence BA AZD2389 Participants will receive a single dose of Treatment B (AZD2389 + quinidine) in Period 1 and a single dose of Treatment A (AZD2389) in Period 2. Sequence BA Quinidine Participants will receive a single dose of Treatment B (AZD2389 + quinidine) in Period 1 and a single dose of Treatment A (AZD2389) in Period 2.
- Primary Outcome Measures
Name Time Method Ratio of Test treatment (AZD2389 + quinidine) to Reference treatment (AZD2389) based on maximum observed plasma concentration (RCmax) Day 1 to Day 10 To assess the effect of quinidine on the PK of AZD2389.
Ratio of Test treatment (AZD2389 + quinidine) to Reference treatment (AZD2389) based on area under concentration-time curve from time 0 to infinity (RAUCinf) Day 1 to Day 10 To assess the effect of quinidine on the PK of AZD2389.
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) Day 1 to Day 10 To assess the effect of quinidine on the PK of AZD2389.
- Secondary Outcome Measures
Name Time Method Apparent total body clearance (CL/F) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Volume of distribution (apparent) following extravascular administration (based on terminal phase) (Vz/F) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Terminal elimination half-life (t1/2λz) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Time to reach maximum observed concentration (tmax) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Maximum observed plasma concentration (Cmax) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Area under concentration-time curve from time zero to infinity (AUCinf) of AZD2389 Day 1 to Day 10 To assess the plasma PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Renal Clearance (CLR) of AZD2389 from plasma Day 1 to Day 10 To assess the urine PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe[t1-t2]) of AZD2389 Day 1 to Day 10 To assess the urine PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 (Ae[t1-t2]) of AZD2389 Day 1 to Day 10 To assess the urine PK of AZD2389 when AZD2389 is administered alone or in combination with quinidine.
Percent change from baseline in fibroblast activation protein (FAP) inhibition Baseline, Day 1 to Day 10 To assess the pharmacodynamics (PD) of AZD2389 by assessment of inhibition of FAP activity in plasma after single oral dose of AZD2389 alone or in combination with quinidine.
Number of participants with Adverse Events (AEs) From Screening (Day -28 to Day -2) to Follow-up visit (upto 8 weeks) To assess the safety and tolerability of a single oral dose of AZD2389 alone or in combination with quinidine in healthy participants.
Trial Locations
- Locations (1)
Research Site
🇺🇸Brooklyn, Maryland, United States