{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:53:11Z","timestamp":1789609991400,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,11,9]],"date-time":"2011-11-09T00:00:00Z","timestamp":1320796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Transient receptor potential vanilloid 1(TRPV1) receptor antagonists have the potential to be used in a wide variety of indications. Whilst many compounds have been evaluated pre\u2010clinically, published clinical data are sparse. A possible dose\u2010limiting effect of TRPV1 antagonists is their potential to cause hyperthermia.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003This study reports the safety and pharmacokinetic data for XEN\u2010D0501, a novel TRPV1 antagonist, in healthy subjects including effects on body temperature.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold>XEN\u2010D0501, a novel TRPV1 antagonist, is being developed to treat overactive bladder. This study investigated the safety and pharmacokinetics of repeat\u2010dose XEN\u2010D0501 in healthy subjects.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold>The study was conducted in two parts. Part 1 was a double\u2010blind, randomized, placebo\u2010controlled, two\u2010way crossover study in three cohorts of 12 young male subjects. Each subject received XEN\u2010D0501 and placebo (in random order) twice daily for 13 days, with a final single dose on day 14. Doses of 1, 2.5 and 5\u2003mg XEN\u2010D0501 were investigated. Part 2 was an open\u2010label, randomized, two\u2010way crossover study in male and female subjects (45 to 65 years). Subjects received single doses of 5\u2003mg XEN\u2010D0501 under fasted and fed conditions in random order. Blood sampling and safety assessments were conducted throughout the study.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>XEN\u2010D0501 was rapidly absorbed (<jats:italic>t<\/jats:italic><jats:sub>max<\/jats:sub>generally 0.5\u20134\u2003h post dose). XEN\u2010D0501 exposure increased less than proportionally to dose over the range studied and exhibited minimal accumulation with twice daily dosing. Food had no clinically relevant effects on the pharmacokinetics of XEN\u2010D0501. There were no severe or serious adverse events and all doses were well tolerated. A dose\u2010related increase in body temperature was seen with XEN\u2010D0501 which attenuated over time. Differences from placebo in mean maximum core body temperatures were 0.22\u00b0C, 0.5\u00b0C and 0.74\u00b0C following 1\u2003mg, 2.5\u2003mg and 5\u2003mg twice daily XEN\u2010D0501. The observed increase in body temperature was not considered to be of clinical concern.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold>XEN\u2010D0501 appeared safe and well tolerated at doses up to 5\u2003mg twice daily for 14 days in healthy subjects.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2011.04040.x","type":"journal-article","created":{"date-parts":[[2011,6,16]],"date-time":"2011-06-16T22:10:07Z","timestamp":1308262207000},"page":"921-931","source":"Crossref","is-referenced-by-count":63,"title":["An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN\u2010D0501 in healthy subjects"],"prefix":"10.1111","volume":"72","author":[{"given":"Patrick","family":"Round","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Priestley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,9]]},"reference":[{"issue":"1","key":"e_1_2_7_2_2","first-page":"S1","article-title":"Guide to Receptors and Channels (GRAC), 4th edition","volume":"158","author":"Alexander SPH","year":"2009","journal-title":"Br J Pharmacol"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/nau.10052"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(02)01784-3"},{"key":"e_1_2_7_5_2","unstructured":"AbramsP JacksonS MattiassonA KrishnanK HaendlerL.A randomized double\u2010blind placebo controlled dose ranging study of the safety and efficacy of tolterodine in patients with hyperreflexia. 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