Prucalopride in Pediatric Subjects With Functional Constipation

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Functional Constipation

Intervention / Treatment
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* Drug: prucalopride
* Drug: Placebo
* Drug: PEG 4000


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Boys and girls, aged ≥ 6 months and < 18 years. Subjects with a confirmed diagnosis of functional constipation as defined by the Rome III criteria. Main Exclusion Criteria: Children with underlying GI abnormalities and causes for defecation disorders. Constipation is thought to be drug-induced. Subjects suffering from secondary causes of chronic constipation.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: prucalopride<br>drug | Drug: prucalopride<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching oral solution or oral tablets given once daily<br>|
| Active Comparator: PEG 4000<br>4-20g administered as an oral solution once daily | Drug: PEG 4000<br> <br> |

What is the study measuring?
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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 |