{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:27:58Z","timestamp":1773030478999,"version":"3.50.1"},"reference-count":8,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T00:00:00Z","timestamp":1391558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Colorectal Disease"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to assess the effects of a single dose of 10\u00a0mg NRL001 (the 1R,2S stereoisomer of methoxamine hydrochloride) in a 2\u00a0g suppository on pharmacodynamic and pharmacokinetic (PK) variables, and safety, in a healthy elderly population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a Phase I, single\u2010centre, randomised, double\u2010blind, placebo\u2010controlled crossover study during which subjects received a single 2\u00a0g suppository of 10\u00a0mg NRL001 and a matching placebo in two separate treatment periods. The main outcome measures were Holter\u2010, vital signs\u2010 and electrocardiogram\u2010derived cardiovascular variables; plasma PK analysis; and safety assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010six subjects were dosed with study medication. Statistically significant reductions in Holter\u2010derived heart rate (HR), vital signs\u2010derived HR and diastolic blood pressure (BP) were observed comparing NRL001 with placebo treatment, and also with increasing NRL001 plasma concentration. No statistically significant relationships were observed between NRL001 concentration and systolic BP, mean arterial pressure or QT<jats:sub>C<\/jats:sub> interval (both Bazett's and Fridericia's correction). Thirty\u2010nine adverse events were reported in 20 (76.9%) subjects, mostly after dosing with NRL001.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Administration of NRL001 suppositories led to decreases in HR when compared with placebo data. NRL001 was well tolerated with a good safety profile during the study. Healthy elderly subjects did not show significantly different biological responses to NRL001 suppositories compared with younger healthy volunteers in previous studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/codi.12543","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T02:21:30Z","timestamp":1391653290000},"page":"27-35","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A randomised, controlled, crossover study to investigate the pharmacodynamics, pharmacokinetics and safety of 1R,2S\u2010methoxamine hydrochloride (NRL001) in healthy elderly subjects"],"prefix":"10.1111","volume":"16","author":[{"given":"D.","family":"Bell","sequence":"first","affiliation":[{"name":"BioKinetic Europe Limited Belfast UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Duffin","sequence":"additional","affiliation":[{"name":"BioKinetic Europe Limited Belfast UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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