Prucalopride was well tolerated in children with functional constipation but not more effective than placebo, according to new research data.
From April 2011 to March 2013, researchers in Europe performed a multicenter phase 3 trial of prucalopride (Resolor, Shire-Movetis), a selective, high-affinity 5-hydroxytryptamine receptor agonist that enhances gastrointestinal motility, to evaluate its safety and efficacy in 213 children with functional constipation.
Patients were aged 6 months to 18 years, with 25% younger than 4 years, 50% aged 4 to 11 years, 25% aged 12 to 18 years; 55.4% were girls. During the 8-week double blind period of the trial, participants were randomly assigned prucalopride (n=106) or placebo (n=107) once per day. Prucalopride dose and delivery method was based on weight, with children weighing ≤50 kg receiving 0.04 mg/kg oral solution, and children weighing >50 kg receiving a 2-mg tablet, with dose adjustments after 4 weeks. A 16-week open-label, active-controlled period followed.
The proportions of patients who met the primary responder definition (a mean of at least three spontaneous bowel movements per week and no more than one fecal incontinence episode per 2 weeks during weeks 5-8) was comparable with prucalopride and placebo (17% vs. 17.8%; P=.9). The primary efficacy endpoint was achieved by 13.6% of patients receiving prucalopride tablets, 17.9% receiving prucalopride oral solution, 18.5% receiving placebo tablets and 17.5% receiving placebo oral solution. Subgroup analysis yielded similar results, and treatment emergent adverse events also were similar, with 69.8% of the prucalopride group reporting adverse events (tablet: 81.8%; solution: 66.7%) compared with 60.7% of the placebo group.
This trial “showed that prucalopride, although generally well tolerated, was not more effective than placebo in pediatric patients with constipation,” the researchers concluded. “This is in contrast to its efficacy in adults, and is supportive of a need for more effective drugs to treat childhood constipation.”
According to an accompanying editorial by Samuel Nurko, MD, from the Center for Motility and Functional and Gastrointestinal Disorders at Boston Children’s Hospital, and Miguel Saps, MD, a pediatric gastroenterologist from the Ann & Robert H. Lurie Children’s Hospital of Chicago, “Prucalopride is not the first type of therapy for [functional constipation] where there have been different outcomes between adults and children.” Biofeedback, for example, has been shown to have high efficacy in adult patients with dyssynergic defecation, but no beneficial effect in children with defecation abnormalities, they wrote.
“Despite the disappointing results of this clinical trial, the study may help to provide further insight to the differences in mechanisms underlying [functional constipation] in adults and children and the optimal design of randomized controlled trials in children,” they concluded.
For more information:
Mugie SM. Gastroenterology. 2014;147:1285-1295.
Nurko S. Gastroenterology. 2014;147:1214-1216.
Disclosure: Some of the researchers are employees of Shire or former employees of Shire-Movetis. See the study for a full list of relevant financial disclosures. Nurko and Saps report no relevant financial disclosures.