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Abstract: PO0751

Phase 1c Study of the Aldosterone Synthase Inhibitor BI 690517 in Diabetic Patients with Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Bornstein, Stefan Richard, University Hospital Carl Gustav Carus, Dresden, Germany
  • de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands
  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Schulze, Friedrich, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Cronin, Lisa, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Wenz, Arne, Boehringer Ingelheim International GmbH, Ingelheim, Rheinland-Pfalz, Germany
  • Tuttle, Katherine R., University of Washington, Seattle, Washington, United States
  • Hadjadj, Samy, University Hospital Center Nantes, Nantes, France
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
Background

Preclinical studies showed aldosterone synthase inhibitors (ASis) to be beneficial in diabetic nephropathy. This placebo (PBO)-controlled, multiple dose, Phase Ic study (NCT03165240) assessed the safety and efficacy of the selective ASi BI 690517 in diabetic patients with kidney disease and albuminuria.

Methods

Patients with type 1 or type 2 diabetes, estimated glomerular filtration rate (eGFR) 20–75 mL/min/1.73m2 and urine albumin creatinine ratio (UACR) 200–3500 mg/g, receiving stable angiotensin receptor blocker/angiotensin-converting enzyme inhibitor treatment were randomised to receive daily oral BI 690517 (3/10/40 mg), eplerenone (25–50 mg) or PBO for 28 days. Drug related adverse events (DRAEs) and seated systolic blood pressure (SBP) were recorded to assess safety. Efficacy was assessed by the proportion of responders, defined as patients with ≥20% decrease from baseline UACR (measured in first morning void [UACRFMV] and 10-h urine [UACR10h] [10/40 mg only]). Due to COVID-19, eplerenone and BI 690517 40 mg group enrolment were stopped early; BI 690517 doses were compared with matching PBO pooled from all dose groups.

Results

IIn total, 58 patients (3 mg n=18; 10 mg n=13; 40 mg n=14; eplerenone n=4; PBO n=9) with median baseline UACR of 873.5 mg/g and eGFR of 41.0 mL/min/1.73m2 were treated. DRAEs occurred in 8 patients (14.8%), all receiving BI 690517; the most frequent were constipation and hyperkaliaemia (both 3.7%, n=2). Treatment was prematurely discontinued in 5 patients (9.3%: BI 690517 n=4; PBO n=1), 2 cases (3.7%) due to DRAEs. Changes seen in SBP did not differ between PBO and BI 685509 dose groups. Compared with PBO, the proportion of patients receiving BI 690517 classed as responders was higher for UACRFMV (PBO 37.5% vs 3 mg 61.1%; 10 mg 53.8%; 40 mg 80.0%) but similar for UACR10h (PBO 50.0% vs 10 mg 50.0%; 40 mg 60.0%).

Conclusion

BI 690517 was generally well tolerated and appears to have an early effect on UACR, with over 50% of treated patients being classed as responders. These data need to be confirmed in larger studies.

Funding

  • Commercial Support – Boehringer Ingelheim