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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05309785
Other study ID # 2022-8410
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date November 24, 2022
Est. completion date February 1, 2025

Study information

Verified date December 2022
Source McGill University Health Centre/Research Institute of the McGill University Health Centre
Contact Norka Rios
Phone 514-934-1934
Email norka.rios@muhc.mcgill.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 44
Est. completion date February 1, 2025
Est. primary completion date August 1, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
Canada McGill University Health Center Montreal Quebec

Sponsors (1)

Lead Sponsor Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in urinary excretion of phosphate from baseline For substudy 1 After =12 weeks of treatment with each dose
Other Peak plasma concentration (Cmax) For substudy 2 8 days
Other Time to peak plasma concentration (tmax) For substudy 2 8 days
Other Trough plasma concentration (Cmin) For substudy 2 8 days
Other Effective half-life (t1/2) For substudy 2 8 days
Primary The 26-week change in albuminuria compared to baseline, as assessed by the UACR. For substudy 1 26 weeks
Primary 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 Change in UACR with 300 mg (at 26 weeks) vs. 100 mg dose (at 12 weeks) vs. baseline For substudy 1 At 12 and 26 weeks
Secondary Change in 24-hour ambulatory blood pressure (BP) For substudy 1 At 12 and 26 weeks
Secondary Area under the plasma concentration versus time curve (AUC) For substudy 1 At 12 and 26 weeks
Secondary Change in 6-minute walk distance from baseline For substudy 1 At 12 and 26 weeks
Secondary Change in urinary excretion of sodium from baseline For substudy 1 At 12 and 26 weeks
Secondary Neutrophil gelatinase-associated lipocalin (NGAL) levels For substudy 1 After =12 weeks of treatment with each dose
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