TY - JOUR
T1 - Efficacy and safety of imarikiren in patients with type 2 diabetes and microalbuminuria
T2 - A randomized, controlled trial
AU - Ito, Sadayoshi
AU - Kagawa, Tomoya
AU - Saiki, Takuya
AU - Shimizu, Kohei
AU - Kuroda, Shingo
AU - Sano, Yuhei
AU - Umeda, Yuusuke
N1 - Funding Information:
This study was funded by Takeda Pharmaceutical Company Limited. Medical writing assistance was provided by BlueMomentum, an Ashfield company, and supported by Takeda Pharmaceuticals Limited.
Publisher Copyright:
© 2019 by the American Society of Nephrology.
PY - 2019/3/7
Y1 - 2019/3/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062595606&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062595606&partnerID=8YFLogxK
U2 - 10.2215/CJN.07720618
DO - 10.2215/CJN.07720618
M3 - Article
C2 - 30755452
AN - SCOPUS:85062595606
VL - 14
SP - 354
EP - 363
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
SN - 1555-9041
IS - 3
ER -
