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OpenTrials
Completed

NCT Number: NCT05309785

Safety and Efficacy of Canagliflozin in Advanced CKD

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.

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Key information

Conditions

ESRD CKD Stage 4 CKD Stage 5 Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

McGill University Health Center

Montreal, Quebec, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: Canagliflozin 300 mg and 100 mg tablet

Primary outcomes

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

    Time frame: 26 weeks

    For substudy 1

  2. 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.

    Time frame: 8 days

    For substudy 2

Secondary outcomes

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

    Time frame: At 12 and 26 weeks

    For substudy 1

  2. Change in 24-hour ambulatory blood pressure (BP)

    Time frame: At 12 and 26 weeks

    For substudy 1

  3. Area under the plasma concentration versus time curve (AUC)

    Time frame: At 12 and 26 weeks

    For substudy 1

  4. Change in 6-minute walk distance from baseline

    Time frame: At 12 and 26 weeks

    For substudy 1

  5. Change in urinary excretion of sodium from baseline

    Time frame: At 12 and 26 weeks

    For substudy 1

  6. Neutrophil gelatinase-associated lipocalin (NGAL) levels

    Time frame: After ≥12 weeks of treatment with each dose

    For substudy 1

Other outcomes

  1. Change in urinary excretion of phosphate from baseline

    Time frame: After ≥12 weeks of treatment with each dose

    For substudy 1

  2. Peak plasma concentration (Cmax)

    Time frame: 8 days

    For substudy 2

  3. Time to peak plasma concentration (tmax)

    Time frame: 8 days

    For substudy 2

  4. Trough plasma concentration (Cmin)

    Time frame: 8 days

    For substudy 2

  5. Effective half-life (t1/2)

    Time frame: 8 days

    For substudy 2

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Acronym: SIP-AKiD

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Apr 4, 2022
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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