Chronic Kidney DiseasePhase 1NCT07024823
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
A Phase 1 study testing AZD4248 in people with Chronic Kidney Disease, run by AstraZeneca at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- AZD4248
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 5 sitesUnited States
- Study dates
- 9 Jun 2025to 25 Dec 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
5 sites in 1 country
United States5 sites, 4 recruiting
- Active, not recruiting
Research Site
Ann Arbor, Michigan, 48109
- Recruiting
Research Site
Chicago, Illinois, 60643
- Recruiting
Research Site
Glendale, California, 91206
- Recruiting
Research Site
Saint Paul, Minnesota, 55114
- Recruiting
Research Site
San Antonio, Texas, 78215
About this study
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 and to Assess Home Measurements of Creatinine in a Prospective, Non-interventional Cohort Study
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).
Read the detailed description
This is a Phase I, first in human (FIH), randomized, single-blind, placebo-controlled study of AZD4248 involving healthy participants (Parts A and B) and participants with DKD (Part C) and to assess home measurements of creatinine in a prospective, non-interventional cohort in participants with DKD (Part D).
The study consists of 4 parts:
- Part A: SAD. Part A will consist of Parts A1 (single ascending doses in healthy participants), A2 (single dose in healthy Chinese participants), and A3 (IV infusion in healthy participants).
- Part B: MAD. Part B will consist of Parts B1 (multiple ascending doses in healthy participants) and B2 (multiple ascending doses in healthy participants of Japanese descent).
- Part C: Multiple dosing in participants with DKD.
- Part D: Multi-site, non-interventional, prospective cohort evaluation of home-based creatinine self-measurement in participants with DKD.
- Conditions
- Chronic Kidney Disease
- Being tested
- AZD4248, Placebo
- Keywords
- Type 2 Diabetes, Diabetic Kidney Disease, Multiple Ascending Dose, Single Ascending Dose, Creatinine, Food Effect, Pharmacokinetics, Safety
- Medical subject headings
- Renal Insufficiency, Chronic, Diabetes Mellitus, Type 2, Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4248Drug
AZD4248 will be administered orally.
PlaceboDrug
Placebo will be administered orally.
AZD4248Drug
AZD4248 will be administered via IV infusion.
PlaceboDrug
Placebo will be administered via IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Part A1 SAD | Experimental | Participants will receive single ascending oral dose of AZD4248 or placebo. Receives: Drug: AZD4248; Drug: Placebo |
| Part A2 SAD Chinese Cohort | Experimental | Participants will receive single oral dose of AZD4248 or placebo. Receives: Drug: AZD4248; Drug: Placebo |
| Part A3 SAD IV Cohort | Experimental | Participants will receive single IV infusion of AZD4248 or placebo. Receives: Drug: AZD4248; Drug: Placebo |
| Part B1 MAD | Experimental | Participants will receive multiple ascending oral doses of AZD4248 or placebo. Receives: Drug: AZD4248; Drug: Placebo |
| Part B2 MAD Japanese | Experimental | Participants will receive multiple ascending oral doses of AZD4248 or placebo. Receives: Drug: AZD4248; Drug: Placebo |
| Part C Multiple Dosing DKD | Experimental | Participants will receive multiple oral doses of AZD4248 or placebo. Receives: Drug: AZD4248; Drug: Placebo |
| Part D Observational Cohort | No intervention | Participants will participate in home-based creatinine self-measurement. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Day 1 to Day 169
Secondary outcomes (31)
Area under concentration-time curve from time 0 to infinity (AUCinf)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
To assess the impact of food on the PK of AZD4248 following a single oral administration.
Measured: 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)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
To assess the impact of food on the PK of AZD4248 following a single oral administration.
Measured: 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)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: 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)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: 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)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Maximum observed drug concentration (Cmax)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
To assess the impact of food on the PK of AZD4248 following a single oral administration
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Dose normalized Cmax (Cmax/D)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Terminal elimination half-life (t½λz)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Terminal rate constant (λz)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Time delay between drug administration and the first observed concentration (tlag)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3.
Time of last quantifiable concentration (tlast)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Time to reach maximum observed concentration (tmax)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
To assess the impact of food on the PK of AZD4248 following a single oral administration
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Apparent volume of distribution based on the terminal phase (Vz/F)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Absolute bioavailability (F)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3.
Total body clearance (CL)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3, Part B: Days 1-17. Part C: Days 1-17
Volume of distribution at steady state (Vss)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part A1 and A2: Days 1-7, Part A3: Days 1-3.
Area under concentration-time curve in the dose interval (AUCtau)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part B: Days 1-17. Part C: Days 1-17
Dose normalized AUCtau (AUCtau/D)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part B: Days 1-17. Part C: Days 1-17
Accumulation ratio for AUC (Rac AUC)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV adnminstration of AZD4248.
Measured: Part B: Days 1-17. Part C: Days 1-17
Accumulation ratio for Cmax (Rac Cmax)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part B: Days 1-17. Part C: Days 1-17
Temporal change parameter (TCP)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248.
Measured: Part B: Days 1-17. Part C: Days 1-17
Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248
Measured: Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14
Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248
Measured: Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14
Renal clearance (CLR)
To characterize the PK of AZD4248 following oral administration of single and multiple doses or a single IV administration of AZD4248
Measured: Part A: Days 1-2. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14
Percentage change from baseline in plasma target engagement marker
To evaluate the TE of AZD4248 by assessing reduction in plasma target engagement marker following single (oral or IV) and multiple oral dosing of AZD4248.
Measured: Part A: Days 1-5. Part B: Days 1-4 and 11-14. Part C: Days 1-4 and 11-14
Part D: Intra- and inter-participant variability of eGFR derived from laboratory measurements
To assess the intra- and inter-participant variability of monthly laboratory-based creatinine measurements.
Measured: Day 1 to Day 169
Part D: Changes over longitudinal follow-up in participant-reported experience questionnaire on collective participant satisfaction, usability and device acceptability data
To evaluate the usability, user satisfaction, and feasibility of delivering a home self-testing device and its accompanying smartphone application.
Measured: Day 1 to Day 169
Part D: Summary of qualitative insights from optional individual in-depth interview samples
To evaluate the usability, user satisfaction, and feasibility of delivering a self-testing, home self-testing device and its accompanying smartphone application.
Measured: Day 30 to Day 84
Part D: Changes over longitudinal follow-up in site-based staff reported PTSFQ
To assess clinical site staff-reported usability and satisfaction of delivering and management of the home self-testing device and software.
Measured: Day 1 to Day 169
Part D: Estimated glomerular filtration rate (eGFR)
To compare home-based serum creatinine measurements against the standard laboratory measurements.
Measured: Day 1 to Day 169
Part D: Proportion of completed creatinine tests, with completed assessments
To assess the rates of missing data due to missed tests or test errors.
Measured: Day 1 to Day 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2025
- Study start9 Jun 2025
- Primary completion25 Dec 2026 (estimated)
- Study completion25 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07024823
- Sponsor's protocol ID
- D8380C00001
- Status last verified
- Aug 2026
- First submitted
- 9 Jun 2025
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.