Advanced Chronic Liver Disease, Healthy Participants
Conditions
Keywords
Hepatic Fibrosis, Fibroblast Activation Protein Inhibitor
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.
Interventions
DRUGAZD2389
AZD2389 will be administered orally.
DRUGQuinidine
Quinidine will be administered orally.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed