The purpose of the study is to evaluate the dose-response efficacy, safety, and pharmacokinetics (PK) of AZD5718 in participants with proteinuric chronic kidney disease.
The study will be conducted in approximately 118 study centers across 12 countries. The overall study period will be around 28 weeks. Approximately 632 participants comprising of 67% diabetic kidney disease (DKD) and 33% non-DKD participants will be enrolled. After a screening period of up to 4 weeks, the participants will be randomised in a 1:1:1:1 ratio to receive one of the doses of AZD5718 and/or placebo for the first 12 weeks (Day 85 \[treatment period 1\]), with an add-on therapy of 8 weeks of dapagliflozin for all participants from Week 12 to 20 (Day 85 to 141 \[treatment period 2\]). Only participants still taking their assigned treatment from treatment period 1 will progress to treatment period 2. Any participant with urine albumin to creatinine ratio (ACR) \< 30 mg/g at Week 12 will be excluded from treatment period 2. The eligibility check to enter treatment period 2 will be done at Visit 7 (Week 12) using the last available urine ACR result. The final analysis will be done after all participants have completed follow-up period of up to 4 weeks. The expected total study duration, including the Screening Period, for each participant will be at least 28 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
613
Participants will receive once daily oral dose of AZD5718 as per the arms they are randomised, and will continue until Week 20.
Participants will receive once daily oral dose of 10 mg dapagliflozin for 8 weeks as an add-on therapy.
Participants will receive once daily oral dose of placebo matched to AZD5718, and will continue until Week 20.
Change From Baseline in Reduction of Urine Albumin to Creatinine Ratio (ACR) to Week 20
The dose response effect of AZD5718 on urine ACR at 20 weeks was evaluated. Values less than 1 indicate improvement from baseline.
Time frame: Week 1 (Baseline) to Week 20
Change From Baseline in Reduction of Urine ACR to Week 12
The dose response effect of AZD5718 on urine ACR at 12 weeks was evaluated. Values less than 1 indicate improvement from baseline.
Time frame: Week 1 (Baseline) to Week 12
Number of Participants With Adverse Events and Serious Adverse Events
The safety and tolerability profile of AZD5718 treatment was assessed
Time frame: From Screening (Week -4 to 0) to Week 24
Change From Baseline in 24-hours Mean Systolic Blood Pressure to Week 12
The effect of AZD5718 on ambulatory blood pressure was assessed
Time frame: Week 1 (Baseline) to Week 12
Plasma Concentrations of AZD5718
The PK of AZD5718 after repeated oral dosing for 20 weeks was evaluated
Time frame: From Week 2 to Week 20
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
The effect of AZD5718 on renal function was evaluated
Time frame: Week 1 (Baseline), Week 2, Week 4, Week 8, and Week 12
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Research Site
Canoga Park, California, United States
Research Site
La Mesa, California, United States
Research Site
San Carlos, California, United States
Research Site
San Francisco, California, United States
Research Site
Victorville, California, United States
Research Site
Denver, Colorado, United States
Research Site
Jacksonville, Florida, United States
Research Site
Winter Haven, Florida, United States
Research Site
Columbus, Georgia, United States
Research Site
Roseville, Michigan, United States
...and 101 more locations