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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Participants; Advanced Chronic Liver Disease

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06973005

D7930C00007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

Treatment Arm

Experimental group

Description:

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.

Treatment:

Drug: Caffeine

Drug: Bupropion

Drug: Midazolam

Drug: AZD2389