Safety and Efficacy of Canagliflozin in Advanced CKD

Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Study ID
NCT05309785
Phase
PHASE4
Status
Active Not Recruiting

Conditions

  • CKD Stage 4
  • CKD Stage 5
  • ESRD

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Invokana 300 mg and 100 mg tablet — DRUG
    Substudy 1 Patients who fulfill the inclusion criteria and consent to participate will receive canagliflozin 100 mg po daily for 12+2 weeks (phase 1). For participants who have tolerated the drug, canagliflozin will be increased to 300 mg po daily for an additional 12+2 weeks (phase 2) and then stopped. If not tolerated, the dose will be reduced to 100 mg until the end of follow-up. Each phase of 12 weeks is followed by a 2-week window to ascertain surrogate efficacy outcomes. Substudy 2 Patients who fulfill the inclusion criteria and consent to participate will receive canagliflozin 100 mg po daily for 9 days.

Study Details

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.

Key Dates

Start date
Nov 24, 2022
Status verified
Mar 2026
Primary completion
Mar 30, 2026
Completion
Jun 1, 2026

Study Design

Enrollment
35 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Primary Outcome Measure

The 26-week change in albuminuria compared to baseline, as assessed by the UACR. [ Time Frame: 26 weeks ]

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