Clinical trial NCT06973005: A Study to Investigate How Multiple Oral Doses of AZD2389 Affect the Pharmacokinetics of Midazolam, Caffeine, and Bupropion in Healthy Participants
Official title: An Open-label, Fixed Sequence Study in Healthy Participants to Assess the Effect of Multiple Doses of AZD2389 on the Pharmacokinetics of Midazolam, Caffeine, and Bupropion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Chronic Liver Disease
Healthy Participants
Keywords: Hepatic Fibrosis
FAP inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2025-05-15
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the effect of multiple doses of AZD2389 on the pharmacokinetics (PK) of midazolam, caffeine, and bupropion in healthy participants.

Detailed description: This study is an open-label, fixed sequence, 3-period, drug-drug interaction (DDI) study in healthy participants performed at a single Clinical Unit.

The study will comprise:

* A Screening Period of maximum 28 days.
* A Treatment Phase, separated into 3 different periods. Period 1 (Day -2 to Day 4): Participants will receive midazolam and caffeine in combination on Day 1. Participants will receive bupropion on Day 2.

Period 2 (Day 5 to Day 13): Participants will receive AZD2389 for 9 days. Period 3 (Day 14 to Day 18): Participants will first receive AZD2389 with midazolam and caffeine in combination on Day 14. On Day 15, participants will first receive AZD2389 with bupropion. On Days 16 and 17, participants will receive AZD2389.

- A final Follow-up Visit, 7 to 14 days after the last AZD2389 PK sample is taken in Period 3.

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study-specific procedures.
* Participants with suitable veins for cannulation or repeated venipuncture.
* Have a body mass index (BMI) between 18 and 32 kilograms per meter squared (kg/m2) inclusive and weigh at least 50 kilograms (kg) at Screening.

Exclusion Criteria:

* History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk.
* 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 illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
* Any clinically important abnormalities in clinical chemistry, coagulation, hematology, or urinalysis results.
* Any positive result at the Screening Visit for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
* Abnormal vital signs, after 10 minutes supine rest, at the Screening Visit and/or admission to the Clinical Unit (Day -2).
* Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead safety ECG.
* History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
* History of hypersensitivity to DPP4 inhibitors, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to DPP4 inhibitors.
* History of severe dermatological disorders, eg, bullous pemphigoid or Stevens-Johnson syndrome, as judged by the investigator.
* Participants who have previously received AZD2389 within the last 12 months prior to the Screening Visit.
* Known hypersensitivity or previous adverse events associated with midazolam, caffeine, or bupropion.

Primary outcomes:
measure: Ratio of treatment to reference based on Cmax (RCmax)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Ratio of treatment to reference based on AUCinf (RAUCinf)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Ratio of treatment to reference based on AUClast (RAUClast)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Ratio of area under concentration-curve from time 0 to 24 hours post-dose (AUC0-24)
timeFrame: Period 1: Days 1-3; Period 3: Days 15-18.
Secondary outcomes:
measure: Apparent total body clearance (CL/F)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Terminal elimination half-life (t1/2λz)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Terminal rate constant (λz)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Time to reach maximum observed concentration (tmax)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Maximum observed concentration (Cmax)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Area under concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: AUC0-24
timeFrame: Period 1: Days 1-3; Period 3: Days 15-18.
measure: RCmax
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: RAUCinf
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: RAUClast
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Ratio of treatment to reference based on AUC0-24 (RAUC0-24)
timeFrame: Period 1: Days 1-3; Period 3: Days 15-18.
measure: Metabolite to parent ratio of the AUCinf
timeFrame: Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.
measure: Metabolite to parent ratio of the AUC0-24
timeFrame: Period 1: Days 1-3; Period 3: Days 15-18.
measure: Area under concentration-time curve in the dose interval (AUCtau)
timeFrame: Period 2: Days 5-13; Period 3: Day 14.
measure: Observed lowest concentration before the next dose is administered (Ctrough)
timeFrame: Period 2: Days 5-13; Period 3: Day 14.
measure: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Only SAE: -30 to -3 to Day -1. AE and SAE: From Day 1 to Follow-up/Early Termination Visit (Days 25-32)
Other outcomes:
Locations:
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: