A Study to Investigate Safety, Tolerability, PK, and PD of AZD4248 in Healthy Participants, Participants with CKD and Type 2 Diabetes, Assess Home Measurements of Creatinine in a Non-Interventional Cohort, and Assess the Effect of AZD4248 on the PK of Midazolam and Metformin in Healthy Participants

Study identifier:D8380C00001

ClinicalTrials.gov identifier:NCT07024823

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A Phase I Randomized, Single-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4248 Following Single and Multiple Ascending Dose Administration in Healthy Participants and Participants with Chronic Kidney Disease and Type 2 Diabetes, to Assess Home Measurements of Creatinine in a Prospective, Non-Interventional Cohort; and to Assess the Effect of Multiple Doses of AZD4248 on the Pharmacokinetics of Oral Midazolam and Metformin in an Open-Label, Fixed Sequence Design in Healthy Participants

Medical condition

Chronic Kidney Disease

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD4248, Placebo, Midazolam, Metformin

Sex

All

Estimated Enrollment

192

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 09 Jun 2025

Estimated Primary Completion Date: 29 Jan 2027

Estimated Study Completion Date: 29 Jan 2027

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2026 by AstraZeneca

Collaborators

Parexel International LLC

Inclusion and exclusion criteria

Inclusion Criteria

- Healthy participants with suitable veins for cannulation or repeated venipuncture.
Parts A, B, and E:
- Have a body mass index (BMI) between 18 and 30 kilograms per millimeter (kg/m2), inclusive.
- For Chinese participants (Part A2): participants are to be Chinese, defined as having both parents and 4 grandparents who are Chinese. This includes second and third generation participants of Chinese descent whose parents or grandparents are living in a country other than China.
- For Japanese participants (Part B2): participants are to be Japanese, defined as having both parents and 4 grandparents who are Japanese. This includes second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
Part C:
- Have a BMI between 20 and 40 kg/m2, inclusive.
- Have a diagnosis of diabetic kidney disease (DKD).
- Hemoglobin A1C (HbA1c) of ≤ 10.5%.
- Participants are required to be on a stable dose of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 6 weeks prior to Visit 1 and throughout the Screening Period. In addition, participants should be on stable doses of all other medication for ≥ 6 weeks before Screening.
Part D:
- Have a BMI between 20 and 35 kg/m2, inclusive.
- Have a diagnosis of DKD as defined by a) diagnosis of type 2 diabetes (T2D) b) eGFR values and c) urine albumin to creatinine ratio (UACR) values.
- HbA1c of ≤ 10.5%.
- Participants are required to be on a stable dose of ACEi or ARB for at least 6 weeks prior to Visit 1 and throughout the Screening Period. In addition, participants should be on stable doses of all other medication for ≥ 6 weeks before Screening.
- Participants must be able and motivated to use the home creatinine device and smartphone independently by successfully performing the test without assistance from site staff.
- Participants must be able to read and understand English sufficient to participate in site visits and home testing.

Exclusion Criteria

- History of any clinically important disease or disorder which may put the participant at risk because of participation in the study or influence the results.
- Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), Hebpatitis C virus antibody (HCVab), or human immunodeficiency virus (HIV).
Parts A, B, and E:
- History or presence of gastrointestinal, hepatic, or renal disease.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4248.
- Participants who have previously received AZD4248.
Part C:
- History or presence of gastrointestinal, hepatic, or renal disease.
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4248.
- Use of drugs that are strong or moderate CYP3A4 inhibitors/inducers or P-gp inhibitors from within 3 weeks before Screening until the end of the last sample collection.
- Participants who have previously received AZD4248.
- Participants on serum creatinine-altering drugs should be on long-term treatment at a stable dose prior to study entry.
- Expected change of dosing regimen during the study.
- History of clinically significant heart or vascular disease.
- New York Heart Association Class 2, 3, or 4 or history of hospitalization for heart failure within 6 months of screening.
- Ventricular arrhythmias requiring treatment.
- Amputation due to peripheral artery disease.
- Severe chronic obstructive pulmonary disease as judged by the Investigator or hospitalization for exacerbation in the last 6 months.
Part D:
- Participants on serum creatinine-altering drugs should be on long-term treatment at a stable dose prior to study entry.
- Expected change of dosing regimen during the study.

Sort by status

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Arms	Assigned Interventions
Experimental: Part A1 SAD Participants will receive single ascending oral dose of AZD4248 or placebo.	Drug: AZD4248 AZD4248 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part A2 SAD Chinese Cohort Participants will receive single oral dose of AZD4248 or placebo.	Drug: AZD4248 AZD4248 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part A3 SAD IV Cohort Participants will receive single IV infusion of AZD4248 or placebo.	Drug: AZD4248 AZD4248 will be administered via IV infusion. Drug: Placebo Placebo will be administered via IV infusion.
Experimental: Part B1 MAD Participants will receive multiple ascending oral doses of AZD4248 or placebo.	Drug: AZD4248 AZD4248 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part B2 MAD Japanese Participants will receive multiple ascending oral doses of AZD4248 or placebo.	Drug: AZD4248 AZD4248 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part C Multiple Dosing DKD Participants will receive multiple oral doses of AZD4248 or placebo.	Drug: AZD4248 AZD4248 will be administered orally. Drug: Placebo Placebo will be administered orally.
No Intervention: Part D Observational Cohort Participants will participate in home-based creatinine self-measurement.	-
Experimental: Part E Drug-Drug Interaction Cohort Participants will receive a single dose of midazolam and metformin followed by multiple oral doses of AZD4248 with a single dose of midazolam and metformin.	Drug: AZD4248 AZD4248 will be administered orally. Drug: Midazolam Midazolam will be administered orally. Drug: Metformin Metformin will be administered orally.

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]