title: Prucalopride is no more effective than placebo for children with functional constipation.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. Electronic address: s.m.mugie@amc.nl.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Mugie
authors.affiliation: Pediatric Department, Medical College, University of Rzeszów, Rzeszów, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Korczowski
authors.affiliation: Department of Paediatrics, Pándy Kálmán Hospital, Gyula, Hungary.
authors.forename: Piroska
authors.initials: P
authors.lastname: Bodi
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Green
authors.affiliation: Shire-Movetis NV, Turnhout, Belgium.
authors.forename: René
authors.initials: R
authors.lastname: Kerstens
authors.affiliation: Shire-Movetis NV, Turnhout, Belgium.
authors.forename: Jannie
authors.initials: J
authors.lastname: Ausma
authors.affiliation: Shire-Movetis NV, Turnhout, Belgium.
authors.forename: Magnus
authors.initials: M
authors.lastname: Ruth
authors.affiliation: Shire, Wayne, Pennsylvania.
authors.forename: Amy
authors.initials: A
authors.lastname: Levine
authors.affiliation: Division of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Benninga
mesh_terms: D000293:Adolescent; D001572:Benzofurans / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003248:Constipation / Q000188:drug therapy*; D003672:Defecation / Q000187:drug effects*; D004311:Double-Blind Method; D005244:Fecal Impaction / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D058828:Serotonin 5-HT4 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure
chemical_list: D001572:Benzofurans; D058828:Serotonin 5-HT4 Receptor Agonists; C406662:prucalopride
keywords: 5-HT(4) Receptor; Clinical Trial; Pediatric; TEAEs