The study objective is to characterize the pharmacokinetics (PK), pharmacodynamics, and surrogate measures of efficacy for canagliflozin in patients with advanced CKD, including those receiving HD. As the CV and renoprotective effects of SGLT-2 inhibitors appear to be independent of glycemic control, the investigators hypothesize that canagliflozin will reduce albuminuria in patients with advanced CKD in the same manner as observed in patients with higher eGFR. The investigators also hypothesize that the 300 mg dose will be equally safe as the 100 mg dose but will have greater efficacy, given data which suggests efficacy correlates with drug exposure in patients without CKD. Given its negligible renal elimination, the investigators hypothesize that exposure to canagliflozin 100 mg at steady state will not exceed the standard bioequivalence boundary of 80-125% in patients receiving HD, compared with published estimates with the 300 mg dose at steady state in individuals with preserved kidney function.
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
The 26-week change in albuminuria compared to baseline, as assessed by the UACR.
Timeframe: 26 weeks
The drug exposure at steady-state with 100 mg, as expressed by the AUC0-24, compared to published estimates with the 300 mg dose in patients with preserved renal function.
Timeframe: 8 days