Safety and Efficacy of Canagliflozin in Advanced CKD
Summary
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.
Timeline
- Start
- 2022-11-24
- Primary completion
- 2026-04-30
- Completion
- 2026-07-01
Publications
- Results Mavrakanas TA, Marsot A, Tsirella E, Rios N, Gritsas A, Suri RS. Canagliflozin Pharmacokinetics at Steady State in Patients on Maintenance Hemodialysis. Kidney Int Rep. 2024 Aug 8;9(10):3049-3052. doi: 10.1016/j.ekir.2024.07.038. eCollection 2024 Oct. No abstract available.
- Elenjickal EJ, Mavrakanas TA, Gritsas A, Suri RS, Marsot A. Population Pharmacokinetic Modeling of Canagliflozin in Advanced Chronic Kidney Disease. Clin Pharmacokinet. 2025 Nov;64(11):1693-1708. doi: 10.1007/s40262-025-01571-8. Epub 2025 Sep 15.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | CANAGLIFLOZIN ANHYDROUS | Small molecule | 100 mg | Oral |
| Subject | CANAGLIFLOZIN ANHYDROUS | Small molecule | 300 mg | Oral |