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).
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.
Have a BMI between 20 and 40 kg/m2, inclusive.
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).
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.
Sequential
AZD4248
DrugAZD4248 will be administered orally.
Placebo
DrugPlacebo will be administered orally.
AZD4248
DrugAZD4248 will be administered via IV infusion.
Placebo
DrugPlacebo will be administered via IV infusion.
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Treatment groupsSee each treatment group below.
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).
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.
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.
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.
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.
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.
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AstraZeneca
Lead sponsor
Parexel
Collaborator
