{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:17:34Z","timestamp":1762928254385},"reference-count":34,"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>Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well\u2013designed, placebo\u2010controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 (1R,2S\u2010methoxamine), an \u03b1<jats:sub>1<\/jats:sub>\u2013adrenoceptor agonist, in the treatment of faecal incontinence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Libertas is a multicentre, Phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, double\u2013blind, randomised, placebo\u2013controlled, parallel group study. Patient recruitment took place across 55 study centres in <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>urope. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self\u2013administered doses of <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 (5, 7.5 or 10\u00a0mg or placebo in a suppository formulation) for 8\u00a0weeks. The primary objective of Libertas is to assess the impact of once daily administration of <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 on the severity and frequency of incontinence episodes as assessed by the <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>exner score at 4\u00a0weeks, compared with placebo. Secondary outcomes include measures of efficacy of <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 compared with placebo following 8\u00a0weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic\/pharmacodynamic relationship to adverse events; dose\u2013response relationship; the efficacy of <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 therapy at 4 and 8\u00a0weeks assessed by the <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>aizey score; and <jats:styled-content style=\"fixed-case\">Q<\/jats:styled-content>o<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> using the <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>aecal <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>ncontinence <jats:styled-content style=\"fixed-case\">Q<\/jats:styled-content>uality of <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>ife and the <jats:styled-content style=\"fixed-case\">EQ<\/jats:styled-content>\u20135<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u20135<jats:styled-content style=\"fixed-case\">L H<\/jats:styled-content>ealthcare <jats:styled-content style=\"fixed-case\">Q<\/jats:styled-content>uestionnaires following 4 and 8\u00a0weeks <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 therapy. Overall patient satisfaction with the treatment will also be evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This is the first randomised controlled study to investigate the efficacy and safety of a selective \u03b1<jats:sub>1<\/jats:sub>\u2013adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of <jats:styled-content style=\"fixed-case\">NRL<\/jats:styled-content>001 on assessments of <jats:styled-content style=\"fixed-case\">Q<\/jats:styled-content>o<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre.<\/jats:p><\/jats:sec>","DOI":"10.1111\/codi.12546","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T02:21:30Z","timestamp":1391653290000},"page":"59-66","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Libertas: rationale and study design of a multicentre, <scp>P<\/scp>hase <scp>II<\/scp>, double\u2013blind, randomised, placebo\u2013controlled investigation to evaluate the efficacy, safety and tolerability of locally applied <scp>NRL<\/scp>001 in patients with faecal incontinence"],"prefix":"10.1111","volume":"16","author":[{"given":"L.","family":"Siproudhis","sequence":"first","affiliation":[{"name":"Gastroenterology Unit CHU Pontchaillou Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Jones","sequence":"additional","affiliation":[{"name":"Norgine Limited Uxbridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Ng Kwet Shing","sequence":"additional","affiliation":[{"name":"Norgine Limited Uxbridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Norgine Limited Uxbridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. H.","family":"Scholefield","sequence":"additional","affiliation":[{"name":"Division of Surgery Queen's Medical Centre University Hospital Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Libertas Study Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,2,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0193945909356098"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/jig.19952"},{"key":"e_1_2_8_4_1","first-page":"33","article-title":"Epidemiology of fecal incontinence: the silent affliction","volume":"91","author":"Johanson JF","year":"1996","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/947694"},{"key":"e_1_2_8_6_1","unstructured":"National Institute for Health and Clinical Excellence.Faecal Incontinence: The Management of Faecal Incontinence in Adults. 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