PMID- 38497241
OWN - NLM
STAT- Publisher
LR  - 20240318
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
DP  - 2024 Mar 18
TI  - Aldosterone synthase inhibitor (BI 690517) therapy for people with diabetes and 
      albuminuric chronic kidney disease: A multicentre, randomized, double-blind, 
      placebo-controlled, Phase I trial.
LID - 10.1111/dom.15518 [doi]
AB  - AIM: This Phase I study evaluated the safety and early efficacy of an aldosterone 
      synthase inhibitor (BI 690517) in people with diabetes and albuminuric chronic 
      kidney disease. METHODS: Double-blind, placebo-controlled study (NCT03165240) at 
      40 sites across Europe. Eligible participants [estimated glomerular filtration 
      rate >/=20 and <75 ml/min/1.73 m(2) ; urine albumin/creatinine ratio (UACR) >/=200 
      and <3500 mg/g] were randomized 6:1 to receive once-daily oral BI 690517 3, 10 or 
      40 mg, or eplerenone 25-50 mg, or placebo, for 28 days. The primary endpoint was 
      the proportion of participants with drug-related adverse events (AEs). Secondary 
      endpoints included changes from baseline in the UACR. RESULTS: Fifty-eight 
      participants were randomized and treated from 27 November 2017 to 16 April 2020 
      (BI 690517: 3 mg, n = 18; 10 mg, n = 13; 40 mg, n = 14; eplerenone, n = 4; 
      placebo, n = 9) for 28 days. Eight (13.8%) participants experienced drug-related 
      AEs [BI 690517: 3 mg (two of 18); 10 mg (four of 13); 40 mg (two of 14)], most 
      frequently constipation [10 mg (one of 13); 40 mg (one of 14)] and hyperkalaemia 
      [3 mg (one of 18); 10 mg (one of 13)]. Most AEs were mild to moderate; one 
      participant experienced severe hyperkalaemia (serum potassium 6.9 mmol/L; BI 
      690517 10 mg). UACR responses [>/=20% decrease from baseline (first morning void 
      urine) after 28 days] were observed for 80.0% receiving BI 690517 40 mg (eight of 
      10) versus 37.5% receiving placebo (three of eight). Aldosterone levels were 
      suppressed by BI 690517, but not eplerenone or placebo. CONCLUSIONS: BI 690517 
      was generally well tolerated, reduced plasma aldosterone and may decrease 
      albuminuria in participants with diabetes and albuminuric chronic kidney disease.
CI  - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Bornstein, Stefan R
AU  - Bornstein SR
AD  - Universitatsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
FAU - de Zeeuw, Dick
AU  - de Zeeuw D
AUID- ORCID: 0000-0003-3434-7777
AD  - Department of Clinical Pharmacy and Pharmacology University of Groningen, 
      University Medical Center Groningen, Groningen, Netherlands.
FAU - Heerspink, Hiddo J L
AU  - Heerspink HJL
AUID- ORCID: 0000-0002-3126-3730
AD  - Department of Clinical Pharmacy and Pharmacology University of Groningen, 
      University Medical Center Groningen, Groningen, Netherlands.
FAU - Schulze, Friedrich
AU  - Schulze F
AUID- ORCID: 0000-0003-0277-8134
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
FAU - Cronin, Lisa
AU  - Cronin L
AD  - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA.
FAU - Wenz, Arne
AU  - Wenz A
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
FAU - Tuttle, Katherine R
AU  - Tuttle KR
AUID- ORCID: 0000-0002-2235-0103
AD  - Providence Health Care, University of Washington, Spokane, Washington, USA.
FAU - Hadjadj, Samy
AU  - Hadjadj S
AUID- ORCID: 0000-0001-7110-6994
AD  - Nantes Universite, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, 
      France.
FAU - Rossing, Peter
AU  - Rossing P
AUID- ORCID: 0000-0002-1531-4294
AD  - Steno Diabetes Center Copenhagen, Copenhagen, Denmark.
LA  - eng
GR  - Boehringer Ingelheim/
PT  - Journal Article
DEP - 20240318
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
SB  - IM
OTO - NOTNLM
OT  - Phase I-II study
OT  - drug development
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - type 1 diabetes
OT  - type 2 diabetes
EDAT- 2024/03/18 06:43
MHDA- 2024/03/18 06:43
CRDT- 2024/03/18 05:13
PHST- 2024/01/16 00:00 [revised]
PHST- 2023/10/27 00:00 [received]
PHST- 2024/01/24 00:00 [accepted]
PHST- 2024/03/18 06:43 [medline]
PHST- 2024/03/18 06:43 [pubmed]
PHST- 2024/03/18 05:13 [entrez]
AID - 10.1111/dom.15518 [doi]
PST - aheadofprint
SO  - Diabetes Obes Metab. 2024 Mar 18. doi: 10.1111/dom.15518.