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Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease
V. Tesar, K. Ciechanowski, Y. Pei, I. Barash, M. Shannon, R. Li, JH. Williams, M. Levisetti, S. Arkin, A. Serra,
Language English Country United States
Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial
NLK
Free Medical Journals
from 1990 to 1 year ago
PubMed Central
from 2008 to 1 year ago
Europe PubMed Central
from 2008 to 1 year ago
Open Access Digital Library
from 1990-07-01
- MeSH
- Aniline Compounds adverse effects therapeutic use MeSH
- Quinolines adverse effects therapeutic use MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Nitriles adverse effects therapeutic use MeSH
- Polycystic Kidney, Autosomal Dominant drug therapy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
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≥60 ml/min per 1.73 m2, and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥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<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. (ClinicalTrials.gov: NCT01233869).
Department of Nephrology Pomeranian Medical University Szczecin Poland
Division of Nephrology Icahn School of Medicine at Mount Sinai New York New York
Division of Nephrology University Health Network Toronto Ontario Canada
Early Oncology Development and Clinical Research and
Suisse ADPKD Institute of Internal Medicine and Nephrology Klinik Hirslanden Zürich Switzerland
Worldwide Research and Development Pfizer Inc Cambridge Massachusetts
Worldwide Research and Development Pfizer Inc San Diego California
References provided by Crossref.org
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