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
© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd..
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 m2 ; 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Diabetes, obesity & metabolism - (2024) vom: 18. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bornstein, Stefan R [VerfasserIn] |
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| Links: |
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| Themen: |
Drug development |
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| Anmerkungen: |
Date Revised 18.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/dom.15518 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369869273 |
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| 100 | 1 | |a Bornstein, Stefan R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aldosterone synthase inhibitor (BI 690517) therapy for people with diabetes and albuminuric chronic kidney disease |b A multicentre, randomized, double-blind, placebo-controlled, Phase I trial |
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| 500 | |a Date Revised 18.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
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| 520 | |a © 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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 m2 ; 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: BI 690517 was generally well tolerated, reduced plasma aldosterone and may decrease albuminuria in participants with diabetes and albuminuric chronic kidney disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Phase I-II study | |
| 650 | 4 | |a drug development | |
| 650 | 4 | |a pharmacodynamics | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a type 1 diabetes | |
| 650 | 4 | |a type 2 diabetes | |
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| 700 | 1 | |a Heerspink, Hiddo J L |e verfasserin |4 aut | |
| 700 | 1 | |a Schulze, Friedrich |e verfasserin |4 aut | |
| 700 | 1 | |a Cronin, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Wenz, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a Tuttle, Katherine R |e verfasserin |4 aut | |
| 700 | 1 | |a Hadjadj, Samy |e verfasserin |4 aut | |
| 700 | 1 | |a Rossing, Peter |e verfasserin |4 aut | |
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