Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal
incontinence showed an unexpected and sustained placebo response
#MMPMID27075314
Siproudhis L
; Graf W
; Emmanuel A
; Walker D
; Shing RN
; Pediconi C
; Pilot J
; Wexner S
; Scholefield J
Int J Colorectal Dis
2016[Jun]; 31
(6
): 1205-16
PMID27075314
show ga
PURPOSE: Faecal incontinence (FI) is distressing, significantly reduces quality
of life (QoL) and has few pharmacological treatments. The ?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. 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?>?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.
|Demography
[MESH]
|Fecal Incontinence/*drug therapy
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Male
[MESH]
|Methoxamine/adverse effects/pharmacokinetics/*therapeutic use
[MESH]
free
free
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