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

NCT06973005 | Completed Phase 1 FDA Drug

• 1 other identifier: D7930C00007
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Chronic Liver Disease; Healthy Participants

Keywords

Hepatic Fibrosis; FAP inhibitor

Outcome Measures

Primary Outcomes (4)

• Ratio of treatment to reference based on Cmax (RCmax)

  To assess the PK parameter RCmax for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Ratio of treatment to reference based on AUCinf (RAUCinf)

  To assess the PK parameter RAUCinf for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Ratio of treatment to reference based on AUClast (RAUClast)

  To assess the PK parameter RAUClast for midazolam, caffeine, and bupropion in combination with AZD2389 compared to midazolam, caffeine, and bupropion alone.

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Ratio of area under concentration-curve from time 0 to 24 hours post-dose (AUC0-24)

  To assess the PK parameter ratio of AUC0-24 for caffeine in combination with AZD2389 compared to caffeine alone.

  Period 1: Days 1-3; Period 3: Days 15-18.

Secondary Outcomes (18)

• Apparent total body clearance (CL/F)

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Apparent volume of distribution based on the terminal phase (Vz/F)

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Terminal elimination half-life (t1/2λz)

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Terminal rate constant (λz)

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

• Time to reach maximum observed concentration (tmax)

  Period 1: Days 1-4; Period 2: Days 5-13; Period 3: Days 14-18.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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.

Drug: AZD2389; Drug: Midazolam; Drug: Caffeine; Drug: Bupropion

Interventions

AZD2389 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.

Treatment Arm

Midazolam DRUG

Single oral dose on: * Day 1 (co-administered with caffeine) * Day 14 (co-administered with caffeine and AZD2389)

Treatment Arm

Caffeine DRUG

Single oral dose on: * Day 1 (co-administered with midazolam) * Day 14 (co-administered with midazolam and AZD2389)

Treatment Arm

Bupropion DRUG

Single oral dose on: * Day 2 (alone) * Day 15 (co-administered with AZD2389)

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Midazolam; Caffeine; Bupropion

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines; Propiophenones; Ketones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: May 8, 2025
• Primary Completion: July 18, 2025
• Study Completion: July 18, 2025
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (1)