1. Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response
- Author
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R. Ng Kwet Shing, Wilhelm Graf, Anton Emmanuel, C. Pediconi, John H. Scholefield, D Walker, Steven D. Wexner, L. Siproudhis, J. Pilot, Norgine Pharmaceuticals Ltd, Nottingham University Hospitals NHS Trust (NUH), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Uppsala University, Norgine, Nottingham University Hospital, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Agonist ,Male ,Quality of life ,medicine.medical_specialty ,Medicin och hälsovetenskap ,medicine.drug_class ,[SDV]Life Sciences [q-bio] ,Placebo-controlled study ,Placebo ,Alpha-1 receptor agonist ,Medical and Health Sciences ,Methoxamine ,Placebos ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Internal medicine ,Surveys and Questionnaires ,medicine ,Fecal incontinence ,Humans ,Demography ,business.industry ,Gastroenterology ,Faecal incontinence ,NRL001 ,Hepatology ,Middle Aged ,3. Good health ,Surgery ,Treatment Outcome ,Patient Satisfaction ,030220 oncology & carcinogenesis ,Anesthesia ,Episode frequency ,030211 gastroenterology & hepatology ,Original Article ,Female ,medicine.symptom ,business ,Fecal Incontinence ,medicine.drug - Abstract
International audience; PURPOSE: Faecal incontinence (FI) is distressing, significantly reduces quality of life (QoL) and has few pharmacological treatments. The α1-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. METHODS: 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. RESULTS: 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 \textgreater 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. CONCLUSIONS: 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
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