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The study investigated the effect of capmatinib on the pharmacokinetics of a single oral dose of digoxin and rosuvastatin in patients with <jats:italic>MET<\/jats:italic>\u2010dysregulated advanced solid tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a multicentre, open\u2010label, single\u2010sequence study. An oral drug cocktail containing 0.25\u00a0mg digoxin and 10\u00a0mg rosuvastatin was administered to adult patients with <jats:italic>MET\u2010<\/jats:italic>dysregulated advanced solid tumours on Day 1, and then on Day 22 with capmatinib. Between Days 11 and 32, capmatinib 400\u00a0mg was administered twice daily to ensure the attainment of steady state for drug\u2013drug interaction assessment. Pharmacokinetics of cocktail drugs and safety of capmatinib were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010two patients were enrolled. Compared to digoxin alone, the geometric mean ratios (90% confidence interval) of area under the concentration\u2013time curve from time zero to infinity and maximum concentration for digoxin plus capmatinib were 1.47 (1.28, 1.68) and 1.74 (1.43, 2.13), respectively. Compared to rosuvastatin alone, the geometric mean ratios (90% confidence interval) of area under the curve to infinity and maximum concentration for rosuvastatin plus capmatinib were 2.08 (1.56, 2.76) and 3.04 (2.36, 3.92), respectively. Most frequent adverse events (\u226525% for all grades) were nausea, asthenia, constipation, vomiting, peripheral oedema and pyrexia. Most frequent Grade 3\/4 adverse events (\u22655%) were anaemia, pulmonary embolism, asthenia, dyspnoea, nausea and vomiting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrated that capmatinib is an inhibitor of P\u2010gp and BCRP transporters, with clinically relevant drug\u2013drug interaction potential. Capmatinib was well\u2010tolerated and no unexpected safety concerns were observed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14697","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T22:28:38Z","timestamp":1607639318000},"page":"2867-2878","source":"Crossref","is-referenced-by-count":15,"title":["Effect of capmatinib on the pharmacokinetics of digoxin and rosuvastatin administered as a 2\u2010drug cocktail in patients with <i>MET<\/i>\u2010dysregulated advanced solid tumours: A phase I, multicentre, open\u2010label, single\u2010sequence drug\u2013drug interaction study"],"prefix":"10.1111","volume":"87","author":[{"given":"Enrique","family":"Grande","sequence":"first","affiliation":[{"name":"Medical Oncology Department MD Anderson Cancer Center Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Giovannini","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Marriere","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pultar","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamreza","family":"Rahmanzadeh","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Curigliano","sequence":"additional","affiliation":[{"name":"Istituto Europeo di Oncologia, IRCCS  Milan Italy"},{"name":"University of Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Cui","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-68"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203455"},{"issue":"21","key":"e_1_2_10_4_1","first-page":"7345","article-title":"A selective small molecule inhibitor of c\u2010Met kinase inhibits c\u2010Met\u2010dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo","volume":"63","author":"Christensen JG","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1121"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0722"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0166"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.17.7.997"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.1635"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758834011422557"},{"key":"e_1_2_10_11_1","unstructured":"US Food and Drug Administration.Capmatinib oral tablet prescribing information. 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