NCT04759833

A Study of Prucalopride For Functional Constipation in Children and Teenagers

Terminated Phase 3 Results posted Last updated 6 June 2024

What this trial tests

Phase 3 trial testing Prucalopride in Constipation in 175 participants. Terminated before completion.

Timeline

13 July 2021

Primary endpoint
13 November 2023

13 November 2023

Quick facts

Lead sponsor	Takeda
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	175
Start date	13 July 2021
Primary completion	13 November 2023
Estimated completion	13 November 2023
Sites	41 locations across United States

Drugs / interventions tested

• Prucalopride — full drug profile →
• Placebo

Conditions studied

• Constipation — all drugs for Constipation →

Sponsor

Takeda — full company profile →

Who can join

Adults 6 Months to 17, any sex, with Constipation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part A: Change From Baseline in Average Number of Weekly Number of Spontaneous Bowel Movements (SBMs) at Week 12 Primary · Baseline, Week 12

Spontaneous bowel movement was defined as a bowel movement that was not preceded within a period of 24 hours by the intake of rescue medication. The average change from baseline in number of SBMs per week derived from the (e-diary) data, in toilet-trained participants who were at least 3 years of age collected during the placebo-controlled part (Part A) was assessed.

Group	Value	95% CI
Part A: Placebo	1.4	± 1.90
Part A: Low Dose Prucalopride	1.9	± 2.67
Part A: High Dose Prucalopride	0.9	± 1.44

Parts A and B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Primary · From first dose of study drug up to Week 52

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. A serious adverse event (SAE) was any untoward medical occurrence (whether considered to be related to inve

TEAEs

Group	Value	95% CI
Part A: Placebo	15
Part A: Low Dose Prucalopride	24
Part A: High Dose Prucalopride	18
Part B: Low Dose Prucalopride	22
Part B: High Dose Prucalopride	17

TESAEs

Group	Value	95% CI
Part A: Placebo	1
Part A: Low Dose Prucalopride	0
Part A: High Dose Prucalopride	0
Part B: Low Dose Prucalopride	1
Part B: High Dose Prucalopride	1

Parts A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters Primary · From first dose of study drug up to Week 52

Laboratory parameters included blood chemistry, hematology, and urinalysis. Clinically significant laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically significant changes in laboratory parameters (included hematology, blood chemistry, and urinalysis) were reported.

Group	Value	95% CI
Part A: Placebo	0
Part A: Low Dose Prucalopride	0
Part A: High Dose Prucalopride	0
Part B: Low Dose Prucalopride	0
Part B: High Dose Prucalopride	0

Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities Primary · From first dose of study drug up to Week 52

Vital signs included measurement of pulse rate, systolic, and diastolic blood pressure. Clinically significant vital signs assessment was based on investigator interpretation. Number of participants with clinically significant changes in vital signs were reported.

Group	Value	95% CI
Part A: Placebo	0
Part A: Low Dose Prucalopride	0
Part A: High Dose Prucalopride	0
Part B: Low Dose Prucalopride	0
Part B: High Dose Prucalopride	0

Parts A and B: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities Primary · From first dose of study drug up to Week 52

ECG included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals parameters measurement. Clinically significant ECG assessment was based on investigator interpretation. Number of participants with clinically significant changes in ECG were reported.

Group	Value	95% CI
Part A: Placebo	0
Part A: Low Dose Prucalopride	0
Part A: High Dose Prucalopride	0
Part B: Low Dose Prucalopride	0
Part B: High Dose Prucalopride	0

Part A: Change From Baseline in Participants' Weekly Stool Consistency Based on Bristol Stool Form Scale (BSFS) Score at Week 12 Categorized by Age Secondary · Baseline, Week 12

The Bristol Stool Form Scale is a 7-score visual scale to measure stool consistency, 1- Separate hard lumps, hard to pass, 2- Sausage-shaped, but lumpy, 3- Like a sausage but with cracks on the surface, 4- Like a sausage or snake, smooth and soft, 5- Soft blobs with clear-cut edges, 6- Fluffy pieces with ragged edges, a mushy stool, 7- Watery, no solid pieces, entirely liquid. A score of 1 or 2 indicates constipation while a score of 6 or 7 indicates diarrhea. A better score (score of 3 and 4 represent ideal stools as they are easy to defecate while not containing excess liquid, 5 indicates av

Participants <8 Years

Group	Value	95% CI
Part A: Placebo	-0.1	± 16.56
Part A: Low Dose Prucalopride	9.8	± 12.75
Part A: High Dose Prucalopride	7.1	± 6.31

Participants ≥8 Years

Group	Value	95% CI
Part A: Placebo	12.6	± 16.77
Part A: Low Dose Prucalopride	13.1	± 21.15
Part A: High Dose Prucalopride	7.0	± 10.44

Part A: Change From Baseline in Weekly Straining Score Based on a 3-point Likert Scale at Week 12 Secondary · Baseline, Week 12

Straining was assessed based on a 3-point Likert scale: (1=not at all, 2=a little, 3=a lot). A higher score indicates a lot of straining i.e., worsening of the condition. Daily scores were summed to obtain a weekly score ranging from 7 to 21 with higher scores indicating a lot of straining.

Group	Value	95% CI
Part A: Placebo	-5.7	± 8.49
Part A: Low Dose Prucalopride	-5.2	± 5.92
Part A: High Dose Prucalopride	-7.6	± 5.12

Part A: Percentage of Responders Based on Assessment of SBMs Secondary · Baseline through Week 12

Spontaneous bowel movement was defined as a bowel movement that was not preceded within a period of 24 hours by the intake of rescue medication. Responder was defined as a participant having an increase of ≥1 SBM per week compared to Baseline and ≥3 SBMs per week for at least 9 out of the 12 weeks of placebo-controlled part (Part A), including 3 of the last 4 weeks. Percentages are rounded off to the nearest single decimal place.

Group	Value	95% CI
Part A: Placebo	1.9	0 – 0
Part A: Low Dose Prucalopride	3.6	0 – 0
Part A: High Dose Prucalopride	0	0 – 0

Part A: Percentage of Participants With Fecal Incontinence at Week 12 Secondary · Week 12

Fecal incontinence was defined as unintentional smear or liquid stool in the underwear that is not due to poor wiping. Fecal incontinence can only occur in toilet-trained participants. Non-retentive fecal incontinence is diagnosed (must include at least a 1-month history in a child with a developmental age older than 4 years for all the following): (i) defecation in places inappropriate to the sociocultural context, (ii) no evidence of fecal retention, and (iii) after appropriate evaluation, the fecal incontinence cannot be explained by another medical condition. Percentages are rounded off to

Group	Value	95% CI
Part A: Placebo	12.9	0 – 0
Part A: Low Dose Prucalopride	3.0	0 – 0
Part A: High Dose Prucalopride	16.7	0 – 0

Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride Secondary · 1-3 hours post-dose at Baseline (Day 0), 14-26 hours post-dose at Weeks 4, 8 and 12

Baseline (Day 0), 1-3 hours

Group	Value	95% CI
Part A: Low Dose Prucalopride	4.707	± 3.4659
Part A: High Dose Prucalopride	5.903	± 4.0231

Week 4, 14-26 hours

Group	Value	95% CI
Part A: Low Dose Prucalopride	2.607	± 0.7336
Part A: High Dose Prucalopride	3.693	± 2.0613

Week 8, 14-26 hours

Group	Value	95% CI
Part A: Low Dose Prucalopride	2.343	± 1.8725
Part A: High Dose Prucalopride	2.963	± 2.0794

Week 12, 14-26 hours

Group	Value	95% CI
Part A: Low Dose Prucalopride	4.365	± 3.6288
Part A: High Dose Prucalopride	3.001	± 4.5358

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to Week 52. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A: Placebo

Serious: 1/56 (2%)

Deaths: 0/56

Part A: Low Dose Prucalopride

Serious: 0/60 (0%)

Deaths: 0/60

Part A: High Dose Prucalopride

Serious: 0/59 (0%)

Deaths: 0/59

Part B: Low Dose Prucalopride

Serious: 1/72 (1%)

Deaths: 0/72

Part B: High Dose Prucalopride

Serious: 1/62 (2%)

Deaths: 0/62

Serious adverse events (4 terms)

Reaction	System	Part A: Placebo	Part A: Low Dose Prucalopr…	Part A: High Dose Prucalop…	Part B: Low Dose Prucalopr…	Part B: High Dose Prucalop…
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—
Intentional self-injury	Psychiatric disorders	—	—	—	—	—
Suicidal ideation	Psychiatric disorders	—	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Part A: Placebo	Part A: Low Dose Prucalopr…	Part A: High Dose Prucalop…	Part B: Low Dose Prucalopr…	Part B: High Dose Prucalop…
Headache	Nervous system disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—

Most-reported serious reactions: Abdominal pain, Depression, Intentional self-injury, Suicidal ideation.

Data from ClinicalTrials.gov NCT04759833 adverse events section.

Sponsor's own description

Functional constipation is a condition when it is very hard to pass a stool that is not due to any other health problem or to medicines being taken. This condition is more common in children and teenagers.

This study has 2 parts:

The main aim of the 1st part of the study is to learn if a medicine called prucalopride can improve bowel movements in children and teenagers with functional constipation. Another aim is to check for side effects from 2 different doses of prucalopride. The main aim of the 2nd part of the study is to continue to check for side effects from 2 different doses of prucalopride.

In the 1st part, at the first visit, the study doctor will check who can take part. Participants who take part will be picked for 1 of 3 treatments by chance.

* A low dose of prucalopride once a day.
* A higher dose of prucalopride once a day.
* A placebo once a day. In this study, a placebo will look like prucalopride but will not have any medicine in it. Participants will be treated with prucalopride or a placebo for 12 weeks.

Participants who took prucalopride will continue to the 2nd part of the study. They will have the same treatment as they did in the 1st part of the study. They will continue with their treatment for another 36 weeks. Participants who took placebo in the 1st part of the study will receive prucalopride in the 2nd part of the study. They will be picked for a low dose or a high dose of prucalopride by chance.

Participants will visit the clinic a few times during treatment. The clinic staff will also telephone the participants, or their parents or caregivers throughout treatment for a check-up 4 weeks after last treatment, the clinic staff will telephone the participants, or their parents or caregivers for a final check-up.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. An Update of Pharmacological Management in Children with Functional Constipation.
   de Geus A, Koppen IJN, Flint RB, Benninga MA, et al · · 2023 · cited 25× · PMID 36941393 · DOI 10.1007/s40272-023-00563-0
2. Design of a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of prucalopride in pediatric patients with functional constipation.
   Cuffari C, Spalding W, Achenbach H, Thakur M, et al · · 2023 · cited 2× · PMID 37215389 · DOI 10.1016/j.conctc.2023.101144