Safety and Efficacy of Canagliflozin in Advanced CKD

NCT ID: NCT05309785

Last Updated: 2025-01-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-24
• Study Completion Date: 2026-06-01

Brief 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.

Detailed Description

Substudy 1:

Patients with eGFR<30 ml/min/1.73m2 and urine albumin to creatinine ratio (UACR)>200 mg/g not receiving dialysis will receive canagliflozin 100 mg po daily for 12 weeks (phase 1). For participants who have tolerated the drug, canagliflozin will be increased to 300 mg po daily for an additional 12 weeks (phase 2) and then stopped. Each phase will be followed by a 2-week window to ascertain surrogate efficacy outcomes.

Substudy 2:

Adult patients on HD for at least 3 months without significant residual renal function will receive canagliflozin 100 mg po daily for 9 days.

Conditions

ESRD; CKD Stage 4; CKD Stage 5

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Invokana 300 mg and 100 mg tablet

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.

Intervention Type: DRUG

Other Intervention Names

Canagliflozin 300 mg and 100 mg tablet

Eligibility Criteria

Inclusion Criteria

(Substudy 1- SIP-AKiD-1):

• adult patients with eGFR <30 ml/min/1.73m2
• urine albumin to creatinine ratio (UACR) >200 mg/g
• not receiving dialysis.

(Substudy 2- SIP-AKiD-2):

• adult patients on hemodialysis for at least 3 months
• without significant residual renal function, defined as a urine output <250 ml/24h.

Exclusion Criteria

• Age <18 years
• type 1 diabetes
• history of euglycemic ketoacidosis
• known hypersensitivity to SGLT-2 inhibitors
• recurrent severe genital or urinary tract infections
• history of atraumatic amputation, gangrene, or active skin ulcer
• use within the last 48 h of an SGLT-2 inhibitor or a combined SGLT-1 and SGLT-2 inhibitor
• liver disease defined by an ALT > 3.0 times the upper limit of normal [ULN] or total bilirubin >1.5 times the ULN or liver cirrhosis of any stage
• gastrointestinal surgery or gastrointestinal disorder that could interfere with trial medication absorption
• pregnancy
• currently breastfeeding
• any other clinical condition that would jeopardize patient safety while participating in this trial.
• Patients receiving digoxin, phenobarbital, phenytoin, rifampin, or ritonavir will be excluded if these agents cannot be safely discontinued

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Thomas Mavrakanas

Assistant Professor, Junior Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Mavrakanas, MD

Role: PRINCIPAL_INVESTIGATOR

Research Institute of the McGill University Health Center

Locations

McGill University Health Center

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Norka Rios

Role: CONTACT

norka.rios@muhc.mcgill.ca

514-934-1934

Facility Contacts

Norka Rios

Role: primary

5149341934

References

Elenjickal EJ, Mavrakanas TA, Gritsas A, Suri RS, Marsot A. Population Pharmacokinetic Modeling of Canagliflozin in Advanced Chronic Kidney Disease. Clin Pharmacokinet. 2025 Sep 15. doi: 10.1007/s40262-025-01571-8. Online ahead of print.

Reference Type: DERIVED

PMID: 40952584 (View on PubMed)

Other Identifiers

2022-8410

Identifier Type: -

Identifier Source: org_study_id