A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4248 in Healthy Participants and Participants With Chronic Kidney Disease and Type 2 Diabetes and to Assess Home Measurements of Creatinine in a Non Interventional Cohort

NCT07024823 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: D8380C00001
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 5

Brief Summary

This study will evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses (SAD) and multiple ascending doses (MAD) of AZD4248 administered as an oral solution and intravenous (IV) infusion. Additionally, the study investigates the non-interventional feasibility of home measurement of serum creatinine in participants with diabetic kidney disease (DKD).

Conditions

Chronic Kidney Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Parts A, B, and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  To assess the safety and tolerability of AZD4248 following single oral ascending doses or single IV administration to healthy participants and multiple oral ascending doses to healthy participants and participants with CKD and T2D (DKD).

  From Day 1 to Follow Up visit (Part A: up to 12 days; Part B and C: up to 19 days)

• Part D: Intra- and inter-participant variability of estimated glomerular filtration rate (eGFR) derived from home self-testing device measurements

  To assess intra- and inter-participant variability of twice weekly home-based serum creatinine measurements.

  Day 1 to Day 169

Secondary Outcomes (31)

• Area under concentration-time curve from time 0 to infinity (AUCinf)

  Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17

• Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)

  Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17

• Dose normalized AUClast (AUClast/D)

  Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17

• Dose normalized AUCinf (AUCinf/D)

  Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17

• Apparent total body clearance (CL/F)

  Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17

Study Arms (7)

Part A1 SAD

EXPERIMENTAL

Participants will receive single ascending oral dose of AZD4248 or placebo.

Drug: AZD4248; Drug: Placebo

Part A2 SAD Chinese Cohort

EXPERIMENTAL

Participants will receive single oral dose of AZD4248 or placebo.

Drug: AZD4248; Drug: Placebo

Part A3 SAD IV Cohort

EXPERIMENTAL

Participants will receive single IV infusion of AZD4248 or placebo.

Drug: AZD4248; Drug: Placebo

Part B1 MAD

EXPERIMENTAL

Participants will receive multiple ascending oral doses of AZD4248 or placebo.

Drug: AZD4248; Drug: Placebo

Part B2 MAD Japanese

EXPERIMENTAL

Participants will receive multiple ascending oral doses of AZD4248 or placebo.

Drug: AZD4248; Drug: Placebo

Part C Multiple Dosing DKD

EXPERIMENTAL

Participants will receive multiple oral doses of AZD4248 or placebo.

Drug: AZD4248; Drug: Placebo

Part D Observational Cohort

NO INTERVENTION

Participants will participate in home-based creatinine self-measurement.

Interventions

AZD4248 DRUG

AZD4248 will be administered orally.

Part A1 SAD; Part A2 SAD Chinese Cohort; Part B1 MAD; Part B2 MAD Japanese; Part C Multiple Dosing DKD

Placebo DRUG

Placebo will be administered orally.

Part A1 SAD; Part A2 SAD Chinese Cohort; Part B1 MAD; Part B2 MAD Japanese; Part C Multiple Dosing DKD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (5)

Research Site

Glendale, California, 91206, United States

RECRUITING

Research Site

Chicago, Illinois, 60643, United States

RECRUITING

Research Site

Ann Arbor, Michigan, 48109, United States

RECRUITING

Research Site

Saint Paul, Minnesota, 55114, United States

RECRUITING

Research Site

San Antonio, Texas, 78215, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2; Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Diabetes Complications

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2025
• First Posted: June 17, 2025
• Study Start: June 9, 2025
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• 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 (5)