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Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response
CHU Pontchaillou, Rennes, France..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Univ Coll Hosp, 235 Euston Rd, London, England..
Norgine Ltd, Norgine House,Widewater Pl,Moorhall Rd, Uxbridge UB9 6NS, Middx, England..
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2016 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 31, no 6, 1205-1216 p.Article in journal (Refereed) Published
Abstract [en]

Faecal incontinence (FI) is distressing, significantly reduces quality of life (QoL) and has few pharmacological treatments. The alpha(1)-adrenoceptor agonist NRL001 (1R,2S-methoxamine hydrochloride) improves anal sphincter tone. NRL001 efficacy was evaluated by changes in Wexner scores at week 4 vs. baseline in NRL001-treated patients compared with placebo. Impact of NRL001 on QoL and safety were also assessed. Four hundred sixty-six patients received NRL001 (5, 7.5 or 10 mg) or placebo as suppository, once daily over 8 weeks. Wexner score, Vaizey score and QoL were analysed at baseline, week 4 and week 8. FI episodes and adverse events were recorded in diaries. At week 4, mean reductions in Wexner scores were -3.0, -2.6, -2.6 and -2.4 for NRL001 5, 7.5, 10 mg and placebo, respectively. All reduced further by week 8. As placebo responses also improved, there was no significant treatment effect at week 4 (p = 0.6867) or week 8 (p = 0.5005). FI episode frequency improved for all patients, but not significantly compared with placebo (week 4: p = 0.2619, week 8: p = 0.5278). All patients' QoL improved, but not significantly for all parameters (p > 0.05) except depression/self-perception at week 4 (p = 0.0102) and week 8 (p = 0.0069), compared with placebo. Most adverse events were mild and judged probably or possibly related to NRL001. All groups demonstrated improvement in efficacy and QoL compared with baseline. NRL001 was well-tolerated without serious safety concerns. Despite the improvement in all groups, there was no statistically significant treatment effect, underlining the importance of relating results to a placebo arm.

Place, publisher, year, edition, pages
2016. Vol. 31, no 6, 1205-1216 p.
Keyword [en]
Faecal incontinence, Quality of life, Episode frequency, Alpha-1 receptor agonist, NRL001
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-302234DOI: 10.1007/s00384-016-2585-7ISI: 000376293400013PubMedID: 27075314OAI: oai:DiVA.org:uu-302234DiVA: diva2:957084
Available from: 2016-09-01 Created: 2016-08-31 Last updated: 2016-09-01Bibliographically approved

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