Prucalopride in Pediatric Subjects With Functional Constipation (FC)

Trial Consisting of an 8-week Double-blind Placebo-controlled Part to Evaluate Efficacy, Safety, Tolerability and Pharmacokinetics of Prucalopride in Paediatric Subjects With Functional Constipation, Aged ≥6 Months to <18 Years, Followed by a 16-week Open-label Comparator (PEG) Controlled Part, to Document Safety and Tolerability up to 24 Weeks

To evaluate the efficacy of prucalopride compared to placebo for the treatment of functional constipation in a paediatric population, aged ≥ 6 months to < 18 years. A 16-week open-label comparator (PEG) controlled part will follow, to document safety and tolerability up to 24 weeks.

Study Overview

• Status: Completed
• Conditions: Functional Constipation
• Intervention / Treatment: Drug: prucalopride; Drug: Placebo; Drug: PEG 4000

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Boys and girls, aged ≥ 6 months and < 18 years.
2. Subjects with a confirmed diagnosis of functional constipation as defined by the Rome III criteria.

Main Exclusion Criteria:

1. Children with underlying GI abnormalities and causes for defecation disorders.
2. Constipation is thought to be drug-induced.
3. Subjects suffering from secondary causes of chronic constipation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching oral solution or oral tablets given once daily
Experimental: prucalopride; drug	Drug: prucalopride; prucalopride; subjects with weight ≤50kg: 0.04 mg/kg once daily as oral solution of 0.4 mg/ml; subjects with weight >50 kg: prucalopride 2 mg tablet once daily
Active Comparator: PEG 4000; 4-20g administered as an oral solution once daily	Drug: PEG 4000

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Responders in the Last Four Weeks of the Double-Blind Treatment Period	Responders are defined as subjects with an average spontaneous defecation frequency is ≥3 times per week AND the average number of fecal incontinence episodes per 2 weeks is ≤ 1 episode (only for subjects after acquisition of toileting skills).	Last 4 weeks of double-blind treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects With Bowel Frequency of 3 or More Spontaneous Bowel Movements (SBM) Per Week in the Last Four Weeks of the Double-Blind Treatment Period	Spontaneous Bowel Movements defined as a bowel movement that is not preceded within a period of 24 hours by the intake of a laxative agent or by the use of an enema.	Last 4 weeks of double-blind treatment period
Percent of Subjects With Fecal Incontinence Episodes of 1 or Less Per 2 Weeks in the Last Four Weeks of the Double-Blind Treatment Period	Fecal incontinence is a lack of control over defecation, leading to involuntary loss of bowel contents (only for subjects after acquisition of toileting skills).	Last 4 weeks of double-blind treatment period
Number of Retentive Posturing or Excessive Volitional Stool Retention in the Double-Blind Treatment Period	Purposefully avoiding defecation.	Over the 8 week double blind treatment period
Painful Bowel Movements Score in the Double-Blind Treatment Period	Pain was rated on a 6-point scale (0=no hurt, 1=hurts little bit, 2=hurts little more, 3=hurts even more, 4=hurts whole lot, 5=hurts worst) in subjects of 3 years and older. Lower scores represent less pain.	Over the 8 week double blind treatment period
Stool Consistency Per SBM Score in Children Without Diapers in the Double-Blind Treatment Period	Measured using the 7-point Bristol scale where 1-2 indicate constipation, 3-4 are ideal stools, and 5-7 tending toward diarrhea.	Over the 8 week double blind treatment period
Stool Consistency Per SBM Score in Children With Diapers in the Double-Blind Treatment Period	Measured on a 4-point scale where 1 is constipation, 2-3 is ideal, and 4 is diarrhea.	Over the 8 week double blind treatment period
Large Diameter Stools in the Double-Blind Treatment Period	Large diameter stools make defecation more difficult. Small diameter stools are better.	Over the 8 week double blind treatment period
Abdominal Pain Score in Double-Blind Treatment Period	Pain was rated on a 6-point scale (0=no hurt, 1=hurts little bit, 2=hurts little more, 3=hurts even more, 4=hurts whole lot, 5=hurts worst) in subjects of 3 years and older. Lower scores represent less pain.	Over the 8 week double blind treatment period
Frequency of Toilet Training in the Double-Blind Treatment Period	Only for subjects after acquisition of toileting skills.	Over the 8 week double blind treatment period
Number of Rescue Medications Taken in the Double-Blind Treatment Period		Over the 8 week double blind treatment period
Time to First SBM in the Double-Blind Treatment Period	After intake of the trial medication on Day 1.	Day 1 onwards
Number of SBM Per Week in the Double-Blind Treatment Period		Over the 8 week double blind treatment period
Change From Baseline in the Number of SBM Per Week Over the 8 Week Double Blind Treatment Period		Baseline and over the 8 week double blind treatment period
Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period		2 weeks
Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period		2 weeks
Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period		Over the 8 week double blind treatment period
Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period		Over the 16 week open label treatment period
Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period		Over the 16 week open label treatment period

Collaborators and Investigators

• Sponsor: Shire
• Collaborators: PRA Health Sciences

Publications and helpful links

General Publications

• Mugie SM, Korczowski B, Bodi P, Green A, Kerstens R, Ausma J, Ruth M, Levine A, Benninga MA. Prucalopride is no more effective than placebo for children with functional constipation. Gastroenterology. 2014 Dec;147(6):1285-95.e1. doi: 10.1053/j.gastro.2014.09.005. Epub 2014 Sep 16.
• van Schaick E, Benninga MA, Levine A, Magnusson M, Troy S. Development of a population pharmacokinetic model of prucalopride in children with functional constipation. Pharmacol Res Perspect. 2016 Jun 1;4(4):e00236. doi: 10.1002/prp2.236. eCollection 2016 Aug.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 4, 2011
• First Submitted That Met QC Criteria: April 5, 2011
• First Posted (Estimate): April 6, 2011

Study Record Updates

• Last Update Posted (Actual): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 29, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride
• Other Study ID Numbers: SPD555-303; M0001-C303 (Other Identifier: Movetis); 2010-022402-40 (EudraCT Number)