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.
方法:双盲,在欧洲40个地点进行的安慰剂对照研究(NCT03165240)。符合条件的参与者[估计肾小球滤过率≥20且<75ml/min/1.73m2;尿白蛋白/肌酐比(UACR)≥200且<3500mg/g]随机分为6:1,每天口服一次BI6905173、10或40mg,或者依普利酮25-50毫克,或安慰剂,28天主要终点是药物相关不良事件(AE)的参与者比例。次要终点包括UACR中相对于基线的变化。
结果:从2017年11月27日至2020年4月16日,58名参与者被随机分配并接受治疗(BI690517:3mg,n=18;10毫克,n=13;40毫克,n=14;依普利酮,n=4;安慰剂,n=9)持续28天。八名(13.8%)参与者经历了与药物相关的不良事件[BI690517:3mg(18个中的2个);10mg(13个中的4个);40mg(14个中的2个)],最常见的便秘[10毫克(13之一);40毫克(14之一)]和高钾血症[3毫克(18之一);10毫克(13之一)]。大多数不良事件为轻度至中度;一名参与者出现严重的高钾血症(血清钾6.9mmol/L;BI69051710mg)。接受BI69051740mg(10个中的8个)的80.0%与接受安慰剂(8个中的3个)的37.5%的UACR反应[在28天后从基线(第一个早晨的尿液)下降≥20%]。醛固酮水平受BI690517抑制,但依普利酮或安慰剂不抑制。
结论:BI690517总体耐受性良好,在糖尿病和白蛋白尿慢性肾脏疾病参与者中,血浆醛固酮降低,并可能减少白蛋白尿。