Background and objectives Imarikiren is a novel, potent, and selective direct renin inhibitor that has shown high oral availability during clinical development for the treatment of diabetic nephropathy.Weevaluated the efficacy and safety of imarikiren in patients with type 2 diabetes mellitus and microalbuminuria. Design, setting, participants, & measurements This was a randomized, multicenter, placebo-controlled, doubleblind, phase 2, dose-finding trial.Atotal of 415 patientswere randomized to imarikiren 5, 20, 40, or 80mg; placebo; or candesartan cilexetil 8mg treatment for 12weeks. The primary end pointwas change in log-transformed urine albumin-to-creatinine ratio from baseline to the end of treatment analyzed using analysis of covariance and a fixedsequence testingprocedure. Secondary efficacy endpoints includedurine albumin-to-creatinine ratio at each assessment point and remission and progression rates. Exploratory efficacy end points included eGFR and sitting BP before dosing. Results Changes in the urine albumin-to-creatinine ratio from baseline to the end of treatment were 16% (placebo), -16% (imarikiren 5mg), -27% (imarikiren 20 mg),-38%(imarikiren 40mg),-39%(imarikiren 80 mg), and -31% (candesartancilexetil 8mg).Urine albumin-to-creatinineratioreductions frombaselinewere statisticallysignificant in all imarikirengroupsversusplacebo(P<0.001 each) aswell as for candesartancilexetil 8mgversusplacebo(P<0.001). Remission rates (urine albumin-to-creatinine ratio <30 mg/g creatinine and decreased ≥30% from baseline) were higher in all imarikiren groups versus the placebo group. Incidence of adverse events was higher in the imarikiren 80-mg group (52%) versus placebo (42%) and candesartan cilexetil (43%) groups. Incidence of adverse events for the other imarikiren groups ranged from33% to 42%. Adverse events weremild ormoderate in severity. All imarikiren doses were well tolerated. Conclusions Imarikiren resulted in a dose-dependent improvement in albuminuria compared with placebo, and it was well tolerated in patients with type 2 diabetes mellitus and microalbuminuria.
|Number of pages||10|
|Journal||Clinical Journal of the American Society of Nephrology|
|Publication status||Published - 2019 Mar 7|
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine