{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:57:07Z","timestamp":1782763027191,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Millennium Pharmaceuticals, Inc."},{"name":"Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this phase 1 study was to determine the effects of sapanisertib on the heart rate\u2013corrected QT (QTc) interval in patients with advanced solid tumors. Adult patients with advanced solid tumors were enrolled to receive a single sapanisertib 40\u2010mg dose. Blood samples for pharmacokinetic analysis were collected and electrocardiogram readings were recorded at baseline and up to 48 hours after dosing. Patients could continue to receive sapanisertib 30\u00a0mg once weekly in 28\u2010day cycles for up to 12 months. The primary objective was to characterize the effect of a single dose of sapanisertib (40\u00a0mg) on the QT interval. Secondary objectives were to evaluate safety, tolerability, and pharmacokinetics. Following a single sapanisertib 40\u2010mg dose in 44 patients, the maximum least squares mean (upper bound of 1\u2010sided 95% confidence interval) changes from time\u2010matched baseline were 7.1 milliseconds (11.4 milliseconds) for individual rate\u2010corrected QT interval at 24 hours after dosing, and 1.8 milliseconds (5.6 milliseconds) for Fridericia\u2010corrected QTc at 1 hour post\u2010dose. There was no sapanisertib plasma concentration\u2010dependent increase in the change from time\u2010matched baseline individual rate\u2010corrected QTc interval or Fridericia\u2010corrected QTc. The most common adverse events following sapanisertib 30\u00a0mg once\u2010weekly dosing were nausea (80%), fatigue (61%), vomiting (57%), and decreased appetite (45%). A single sapanisertib 40\u00a0mg dose did not produce clinically relevant effects on QTc interval in patients with advanced solid tumors. The safety profile of sapanisertib 30\u00a0mg once weekly was favorable, and no new safety signals were observed (NCT02197572, clinicaltrials.gov).<\/jats:p>","DOI":"10.1002\/cpdd.808","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T05:25:28Z","timestamp":1591161928000},"page":"876-888","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Phase 1 Study to Evaluate the Effect of the Investigational Anticancer Agent Sapanisertib on the QTc Interval in Patients With Advanced Solid Tumors"],"prefix":"10.1002","volume":"9","author":[{"given":"Chirag","family":"Patel","sequence":"first","affiliation":[{"name":"Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Goel","sequence":"additional","affiliation":[{"name":"Montefiore Medical Center  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists\/Sarah Cannon Research Institute  Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Rangachari","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayson D.","family":"Wilbur","sequence":"additional","affiliation":[{"name":"Metrum Research Group LCC  Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Shou","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Craig","family":"Lockhart","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00487.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.067"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.17.2215"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2009.02.020"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.7.3.305"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_11_8_1","unstructured":"European Medicines Agency.ICH E14 (R3) Clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs \u2010 questions and answers.http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/regulation\/general\/general_content_001080.jsp&mid. 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