Safety and Efficacy of Canagliflozin in Advanced CKD

NCT05309785 | Active Not Recruiting Phase 4

• 1 other identifier: 2022-8410
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

ESRD; CKD Stage 4; CKD Stage 5

Keywords

Canagliflozin; Advanced CKD; ESRD; Hemodialysis; Safety; Efficacy; SGLT-2 inhibitor

Outcome Measures

Primary Outcomes (2)

• The 26-week change in albuminuria compared to baseline, as assessed by the UACR.

  For substudy 1

  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.

  For substudy 2

  8 days

Secondary Outcomes (6)

• Change in UACR with 300 mg (at 26 weeks) vs. 100 mg dose (at 12 weeks) vs. baseline

  At 12 and 26 weeks

• Change in 24-hour ambulatory blood pressure (BP)

  At 12 and 26 weeks

• Area under the plasma concentration versus time curve (AUC)

  At 12 and 26 weeks

• Change in 6-minute walk distance from baseline

  At 12 and 26 weeks

• Change in urinary excretion of sodium from baseline

  At 12 and 26 weeks

Other Outcomes (5)

• Change in urinary excretion of phosphate from baseline

  After ≥12 weeks of treatment with each dose

• Peak plasma concentration (Cmax)

  8 days

• Time to peak plasma concentration (tmax)

  8 days

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.

Also known as: Canagliflozin 300 mg and 100 mg tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• 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

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Center

Montreal, Quebec, Canada

Location

Related Publications (1)

• 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.

  PMID: 40952584 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency, Chronic

Interventions

Canagliflozin; Tablets

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Thomas Mavrakanas, MD

  Research Institute of the McGill University Health Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Junior Scientist

Model Details: We will conduct a single center, prospective, single-arm, open-label interventional study in 2 cohorts. Substudy 1: patients with advanced CKD, not yet on HD (N=36) Substudy 2: patients receiving HD (N=8)

Study Record Dates

• First Submitted: March 14, 2022
• First Posted: April 4, 2022
• Study Start: November 24, 2022
• Primary Completion: March 30, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

CA (1)