Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response
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
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.
Faecal incontinence, Quality of life, Episode frequency, Alpha-1 receptor agonist, NRL001
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-302234DOI: 10.1007/s00384-016-2585-7ISI: 000376293400013PubMedID: 27075314OAI: oai:DiVA.org:uu-302234DiVA: diva2:957084