Premium
Libertas: rationale and study design of a multicentre, P hase II , double–blind, randomised, placebo–controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL 001 in patients with faecal incontinence
Author(s) -
Siproudhis L.,
Jones D.,
Ng Kwet Shing R.,
Walker D.,
Scholefield J. H.
Publication year - 2014
Publication title -
colorectal disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.029
H-Index - 89
eISSN - 1463-1318
pISSN - 1462-8910
DOI - 10.1111/codi.12546
Subject(s) - medicine , tolerability , placebo , adverse effect , clinical trial , quality of life (healthcare) , randomized controlled trial , urinary incontinence , surgery , alternative medicine , nursing , pathology
Aims 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–designed, placebo‐controlled 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 NRL 001 (1R,2S‐methoxamine), an α 1 –adrenoceptor agonist, in the treatment of faecal incontinence. Methods Libertas is a multicentre, Phase II , double–blind, randomised, placebo–controlled, parallel group study. Patient recruitment took place across 55 study centres in E urope. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self–administered doses of NRL 001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL 001 on the severity and frequency of incontinence episodes as assessed by the W exner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL 001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose–response relationship; the efficacy of NRL 001 therapy at 4 and 8 weeks assessed by the V aizey score; and Q o L using the F aecal I ncontinence Q uality of L ife and the EQ –5 D –5 L H ealthcare Q uestionnaires following 4 and 8 weeks NRL 001 therapy. Overall patient satisfaction with the treatment will also be evaluated. Discussion This is the first randomised controlled study to investigate the efficacy and safety of a selective α 1 –adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL 001 on assessments of Q o L , 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.