AZD4248 in healthy adults and people with diabetic chronic kidney disease

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 and to Assess Home Measurements of Creatinine in a Prospective, Non-interventional Cohort Study

This project will test whether single and multiple doses of AZD4248 are safe and how the drug behaves in healthy adults and people with diabetic kidney disease, and will also see if home creatinine testing is practical.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 124 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 5 sites (Glendale, California and 4 other locations)
• Trial ID: NCT07024823 on ClinicalTrials.gov

What this trial studies

This is a Phase I, first-in-human, randomized, single-blind, placebo-controlled protocol that gives single ascending doses (SAD) and multiple ascending doses (MAD) of AZD4248 by oral solution and IV infusion in healthy volunteers and a multiple-dose cohort in people with diabetic kidney disease (DKD). The interventional parts include ethnicity-specific cohorts (healthy Chinese and healthy Japanese participants) and both SAD and MAD escalation to characterize safety, tolerability, pharmacokinetics, and pharmacodynamics. A separate non-interventional arm prospectively tests the feasibility of home-based serum creatinine self-measurement in people with DKD across multiple sites. Participants must meet BMI and other inclusion limits and attend in-person dosing and follow-up visits at the study sites.

Who should consider this trial

Good fit: Ideal candidates are adults who meet the BMI and eligibility windows: healthy volunteers with suitable veins and BMI within specified ranges, or adults with diagnosed diabetic kidney disease with BMI 20–35 kg/m2, HbA1c ≤ 10.5% and stable background medications.

Not a fit: People with advanced or non-diabetic kidney failure, unstable diabetes, significant comorbidities, or those outside the specified BMI or demographic criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If results are favorable, AZD4248 could progress toward a new treatment option for diabetic kidney disease and home creatinine testing could enable easier kidney monitoring.

How similar studies have performed: AZD4248 is being tested first-in-human, so the drug itself is novel at this stage, while feasibility work on home creatinine and early-phase safety testing for kidney drugs has shown mixed but sometimes promising results in prior studies.

Eligibility criteria

Key Inclusion Criteria:

\- Healthy participants with suitable veins for cannulation or repeated venipuncture.

Parts A and B:

* 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 35 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.

Key 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), or human immunodeficiency virus (HIV).

Parts A and B:

* 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.

Where this trial is running

Glendale, California and 4 other locations

• Research Site — Glendale, California, United States (Recruiting)
• Research Site — Chicago, Illinois, United States (Recruiting)
• Research Site — Ann Arbor, Michigan, United States (Recruiting)
• Research Site — Saint Paul, Minnesota, United States (Recruiting)
• Research Site — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Chronic Kidney Disease; Type 2 Diabetes; Diabetic Kidney Disease; Multiple Ascending Dose; Single Ascending Dose; Creatinine; Food Effect; Pharmacokinetics