ESRD Clinical Trial
— SIP-AKiDOfficial title:
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.
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 |
Country | Name | City | State |
---|---|---|---|
Canada | McGill University Health Center | Montreal | Quebec |
Lead Sponsor | Collaborator |
---|---|
McGill University Health Centre/Research Institute of the McGill University Health Centre |
Canada,
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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