Prucalopride Is No More Effective Than Placebo for Children With Functional Constipation

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• 作者：Suzanne M. Mugie¹ ; ^{s.m.mugie@amc.nl" class="auth_mail" title="E-mail the corresponding author} ; Bartosz Korczowski² ; Piroska Bodi³ ; Alexandra Green⁴ ; René ; Kerstens⁵ ; Jannie Ausma⁵ ; Magnus Ruth⁵ ; Amy Levine⁶ ; Marc A. Benninga¹
• 关键词：TEAEs ; 5-HT4 Receptor ; Pediatric ; Clinical Trial
• 刊名：Gastroenterology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：147
• 期：6
• 页码：1285-1295.e1
• 全文大小：726 K

文摘

Prucalopride is a selective, high-affinity agonist of the 5-hydroxytryptamine (serotonin) receptor 4 that enhances motility in the gastrointestinal tract. We performed a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of prucalopride in children (6 months to 18 years old) with functional constipation.

Methods

Children with functional constipation, based on the Rome III criteria, were given prucalopride (children ≤50 kg were given a 0.04 mg/kg oral solution; children >50 kg were given a 2-mg tablet) or placebo once daily for 8 weeks. The primary efficacy end point was the proportion of children with toileting skills who had a mean of ≥3 spontaneous bowel movements/week and ≤1 episode of fecal incontinence/2 weeks, from study weeks 5–8 (responders). Adverse events, clinical laboratory values, and electrocardiograms were monitored.

Results

Efficacy and safety were assessed in 213 children (106 prucalopride, 107 placebo). Twenty-five percent were younger than 4 years old, 50% were 4–11 years old, and 25% were 12–18 years old; 55.4% were girls. At screening, 62.3% of patients in the prucalopride group and 55.1% in the placebo group had a history of fecal incontinence; 60.4% and 55.1% in the prucalopride and placebo groups, respectively, had a mean of ≤1 spontaneous bowel movements/week. The proportion of responders was similar between groups (prucalopride, 17.0% and placebo, 17.8%). There were no statistically significant differences in the primary efficacy end point when patients were stratified by sex, age group, or country. The incidence of treatment-emergent adverse events was similar in the prucalopride (69.8%) and placebo (60.7%) groups.

Conclusions

Prucalopride, although generally well tolerated, was not more effective than placebo in children with functional constipation. ClinicalTrials.gov Number: NCT01330381.