A Study to Investigate How Multiple Oral Doses of AZD2389 Affect the Pharmacokinetics of Midazolam, Caffeine, and Bupropion in Healthy Participants

NCT ID: NCT06973005

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-08
• Study Completion Date: 2025-07-18

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.

Conditions

Advanced Chronic Liver Disease; Healthy Participants

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

In Period 1, participants will receive midazolam and caffeine in combination on Day 1. Participants will receive bupropion on Day 2.

In Period 2, participants will receive AZD2389 for 9 days from Day 5 to Day 13. In Period 3, 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.

Group Type: EXPERIMENTAL

AZD2389

Intervention Type: DRUG

Oral dose on Days 5 to 13, Day 16, and Day 17. On Day 14 co-administered with a combination of midazolam and caffeine. On Day 15 co-administered with bupropion.

Midazolam

Intervention Type: DRUG

Single oral dose on:

• Day 1 (co-administered with caffeine)
• Day 14 (co-administered with caffeine and AZD2389)

Caffeine

Intervention Type: DRUG

Single oral dose on:

• Day 1 (co-administered with midazolam)
• Day 14 (co-administered with midazolam and AZD2389)

Bupropion

Intervention Type: DRUG

Single oral dose on:

• Day 2 (alone)
• Day 15 (co-administered with AZD2389)

Interventions

AZD2389

Oral dose on Days 5 to 13, Day 16, and Day 17. On Day 14 co-administered with a combination of midazolam and caffeine. On Day 15 co-administered with bupropion.

Intervention Type: DRUG

Midazolam

Single oral dose on:

• Day 1 (co-administered with caffeine)
• Day 14 (co-administered with caffeine and AZD2389)

Intervention Type: DRUG

Caffeine

Single oral dose on:

• Day 1 (co-administered with midazolam)
• Day 14 (co-administered with midazolam and AZD2389)

Intervention Type: DRUG

Bupropion

Single oral dose on:

• Day 2 (alone)
• Day 15 (co-administered with AZD2389)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Brooklyn, Maryland, United States

Countries

United States

Other Identifiers

D7930C00007

Identifier Type: -

Identifier Source: org_study_id