The changes include: Substantial Amendment 1 ● As the requirement for the mean UACR to be ≥ 200 mg/g at baseline ensured that participants were randomized with significant levels of albuminuria despite adequate treatment with angiotensin converting enzyme inhibitor (ACEi)/ARB, inclusion criterion 9 (FMV samples) was also to be met at visit 4 and 5. ● The criterion that prohibited sperm donation during the study period was a standard procedure in Astellas sponsored clinical trials and was deleted in error in the original protocol. It was re-introduced. ● As it was deemed important to repeat the electrocardiogram (ECG) during the 4-week follow-up visit, an ECG assessment was added to visit 12. ● There were no drug-related histopathological changes in the male reproductive organs in the 4-week and 13-week repeated dose studies in rats and monkeys. Therefore, it was concluded that the potential for effects on male fertility was low. Hence, the details of follow-up for pregnancy of partners of participating male patients were removed. ● Based on local requirements, certain events that occurred during a participant's participation in the clinical trial were to be reported as adverse events (AEs) or expedited as serious adverse events (SAEs).

The changes include: Substantial Amendment 2 ● In order to further characterize the pharmacokinetic and pharmacodynamic profile and long-term pharmacodynamic and pharmacodynamic profile of the investigational product ASP8232, the follow-up period was extended up to approximately 24 weeks after the EoT visit to cover approximately 5 times the mean terminal elimination halflife of 760 hours. ● In inclusion criteria 10, 11 and 12, the use of contraception for female participants of childbearing potential was extended until 24 weeks after the final study drug administration

The changes include: Substantial Amendment 3 ● In order to facilitate participants’ enrollment into the study, the eGFR entry criterion was extended. The participant must have an eGFR (based on the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) of ≥ 25 and < 75 mL/min/1.73 m2. ● Additional specification of study population for stable treatment for at least 3 months prior to screening was updated. ● Retesting of UACR measurement at visit 2 was allowed if value was between 100 and 200 mg/g. It was allowed to avoid the rejection of participants who were potentially valid candidates for the study, but appeared to be below 200 mg/g due to the day to day variability of albuminuria. ● Rescreening of the participants was allowed once per participant, if the participant was not randomized into this trial before. ● The previous criterion of at least 2 samples out of 3 per triplicate (at visit 4 and visit 5) was considered too strict, therefore this criterion was changed in order to facilitate enrollment. For a participant to be eligible, it is required that the geometric mean UACR of all visit 4 and visit 5 samples is ≥ 200 and ≤ 3000 mg/g AND in at least 3 FMV samples, and the UACR at visit 4 and visit 5 is ≥ 200 mg/g. ● Additional specifications of concomitant medication (and nonmedication therapies) were updated. Carvedilol was removed from the list of the prohibited drugs for pharmacokinetic interferences. ● Additional specification of previous and concomitant treatments was updated. ● Details of study completion date and number of patients participating in the study were updated.