Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10365058" target="_blank" >RIV/00216208:11110/17:10365058 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/17:10365058

Výsledek na webu

<a href="http://dx.doi.org/10.1681/ASN.2016111232" target="_blank" >http://dx.doi.org/10.1681/ASN.2016111232</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1681/ASN.2016111232" target="_blank" >10.1681/ASN.2016111232</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease

Popis výsledku v původním jazyce

Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR &gt;= 60 ml/min per 1.73 m(2), and total kidney volume &gt;= 750 ml were randomized 1: 1: 1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for &lt;= 24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for &gt;= 2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg/d were later reduced to 200 mg/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg/d versus placebo (1.63% versus 4.74%, respectively; P=0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively; P &lt; 0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified.

Název v anglickém jazyce

Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease

Popis výsledku anglicky

Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR &gt;= 60 ml/min per 1.73 m(2), and total kidney volume &gt;= 750 ml were randomized 1: 1: 1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for &lt;= 24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for &gt;= 2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg/d were later reduced to 200 mg/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg/d versus placebo (1.63% versus 4.74%, respectively; P=0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively; P &lt; 0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30217 - Urology and nephrology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of the American Society of Nephrology

ISSN

1046-6673

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

3404-3413

Kód UT WoS článku

000414419000030

EID výsledku v databázi Scopus

2-s2.0-85032629031