Functional Constipation
Conditions
Brief summary
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.
Interventions
DRUGprucalopride
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
DRUGPlacebo
Matching oral solution or oral tablets given once daily
DRUGPEG 4000
Sponsors
PRA Health Sciences
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Responders in the Last Four Weeks of the Double-Blind Treatment Period | Last 4 weeks of 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Over the 8 week double blind treatment period | — |
| 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 | Last 4 weeks of 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. |
| 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 | Last 4 weeks of 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). |
| Number of Retentive Posturing or Excessive Volitional Stool Retention in the Double-Blind Treatment Period | Over the 8 week double blind treatment period | Purposefully avoiding defecation. |
| Painful Bowel Movements Score in the Double-Blind Treatment Period | Over the 8 week 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. |
| Stool Consistency Per SBM Score in Children Without Diapers in the Double-Blind Treatment Period | Over the 8 week 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. |
| Stool Consistency Per SBM Score in Children With Diapers in the Double-Blind Treatment Period | Over the 8 week double blind treatment period | Measured on a 4-point scale where 1 is constipation, 2-3 is ideal, and 4 is diarrhea. |
| Large Diameter Stools in the Double-Blind Treatment Period | Over the 8 week double blind treatment period | Large diameter stools make defecation more difficult. Small diameter stools are better. |
| Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | 2 weeks | — |
| Frequency of Toilet Training in the Double-Blind Treatment Period | Over the 8 week double blind treatment period | Only for subjects after acquisition of toileting skills. |
| 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 | Day 1 onwards | After intake of the trial medication on Day 1. |
| 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 | — |
| 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 | — |
| Abdominal Pain Score in Double-Blind Treatment Period | Over the 8 week 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. |
Countries
Netherlands
Participant flow
Pre-assignment details
Subjects who completed the 8 week double blind treatment period and wished to continue were re-randomized after the double-blind treatment period to the 16 week open-label treatment period. Out of 215 subjects randomized in the study, 213 subjects received treatment and 2 subjects withdrew consent before treatment.
Participants by arm
| Arm | Count |
|---|---|
| Prucalopride Subjects with weight ≤50 kg received 0.04 mg/kg prucalopride once daily as oral solution of 0.4 mg/mL. Subjects with weight \>50 kg received prucalopride 2 mg oral tablet once daily. | 106 |
| Placebo Subjects with weight ≤50 kg received placebo matching to prucalopride oral solution. Subjects with weight \>50 kg received placebo matching to prucalopride oral tablet. | 107 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period (8 Weeks) | Adverse Event | 1 | 1 | 0 |
| Double-blind Treatment Period (8 Weeks) | Did not fulfill inclusion/exclusion | 1 | 0 | 0 |
| Double-blind Treatment Period (8 Weeks) | Lack of Efficacy | 1 | 1 | 0 |
| Double-blind Treatment Period (8 Weeks) | Lost to Follow-up | 1 | 0 | 0 |
| Double-blind Treatment Period (8 Weeks) | Non-compliance | 2 | 1 | 0 |
| Double-blind Treatment Period (8 Weeks) | Withdrawal by Subject | 5 | 4 | 0 |
| Open-label Treatment Period (16 Weeks) | Adverse Event | 2 | 0 | 0 |
| Open-label Treatment Period (16 Weeks) | Non-compliance | 0 | 0 | 1 |
| Open-label Treatment Period (16 Weeks) | Sponsor's decision | 1 | 0 | 1 |
| Open-label Treatment Period (16 Weeks) | Withdrawal by Subject | 7 | 0 | 16 |
Baseline characteristics
| Characteristic | Total | Prucalopride | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 213 Participants | 106 Participants | 107 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.3 years STANDARD_DEVIATION 4.61 | 8.3 years STANDARD_DEVIATION 4.54 | 8.2 years STANDARD_DEVIATION 4.69 |
| Region of Enrollment Belgium | 8 Participants | 4 Participants | 4 Participants |
| Region of Enrollment France | 4 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Germany | 7 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Hungary | 74 Participants | 39 Participants | 35 Participants |
| Region of Enrollment Italy | 3 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Netherlands | 51 Participants | 25 Participants | 26 Participants |
| Region of Enrollment Poland | 46 Participants | 23 Participants | 23 Participants |
| Region of Enrollment United Kingdom | 20 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Female | 118 Participants | 60 Participants | 58 Participants |
| Sex: Female, Male Male | 95 Participants | 46 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 53 / 106 | 50 / 107 | 44 / 98 | 44 / 99 |
| serious Total, serious adverse events | 5 / 106 | 2 / 107 | 4 / 98 | 1 / 99 |
Outcome results
Primary
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).
Time frame: Last 4 weeks of double-blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prucalopride | Percent of Responders in the Last Four Weeks of the Double-Blind Treatment Period | 17.0 percentage of subjects |
| Placebo | Percent of Responders in the Last Four Weeks of the Double-Blind Treatment Period | 17.8 percentage of subjects |
p-value: 0.9002Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Abdominal Pain Score in Double-Blind Treatment Period | 0.9 units on a scale | Standard Deviation 1.18 |
| Placebo | Abdominal Pain Score in Double-Blind Treatment Period | 1.1 units on a scale | Standard Deviation 1.15 |
Secondary
Change From Baseline in the Number of SBM Per Week Over the 8 Week Double Blind Treatment Period
Time frame: Baseline and over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Change From Baseline in the Number of SBM Per Week Over the 8 Week Double Blind Treatment Period | 1.5 SBM/week | Standard Deviation 2.35 |
| Placebo | Change From Baseline in the Number of SBM Per Week Over the 8 Week Double Blind Treatment Period | 1.0 SBM/week | Standard Deviation 1.78 |
Secondary
Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period
Time frame: Over the 16 week open label treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prucalopride | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Neutral | 16.5 percentage of subjects |
| Prucalopride | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Quite difficult | 0.0 percentage of subjects |
| Prucalopride | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Very difficult | 1.0 percentage of subjects |
| Prucalopride | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Very easy | 54.6 percentage of subjects |
| Prucalopride | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Quite easy | 27.8 percentage of subjects |
| Placebo | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Very easy | 47.8 percentage of subjects |
| Placebo | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Quite easy | 28.9 percentage of subjects |
| Placebo | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Neutral | 15.6 percentage of subjects |
| Placebo | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Very difficult | 2.2 percentage of subjects |
| Placebo | Convenience of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Quite difficult | 5.6 percentage of subjects |
p-value: 0.3044Van Elteren test
Secondary
Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Extremely effective | 14.6 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Not at all effective | 33.0 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Little bit effective | 14.6 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Moderately effective | 15.5 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Quite a bit effective | 22.3 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Quite a bit effective | 14.0 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Moderately effective | 25.2 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Not at all effective | 32.7 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Extremely effective | 9.3 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Double-Blind Treatment Period | Little bit effective | 18.7 percentage of subjects |
p-value: 0.4647Van Elteren test
Secondary
Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period
Time frame: Over the 16 week open label treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Little bit effective | 10.3 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Quite a bit effective | 18.6 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Moderately effective | 20.6 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Extremely effective | 20.6 percentage of subjects |
| Prucalopride | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Not at all effective | 29.9 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Extremely effective | 46.2 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Not at all effective | 15.1 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Little bit effective | 5.4 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Moderately effective | 11.8 percentage of subjects |
| Placebo | Efficacy of Treatment for Final On Treatment Assessment in Open-Label Treatment Period | Quite a bit effective | 21.5 percentage of subjects |
p-value: <0.0001Van Elteren test
Secondary
Frequency of Toilet Training in the Double-Blind Treatment Period
Only for subjects after acquisition of toileting skills.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Frequency of Toilet Training in the Double-Blind Treatment Period | 4.9 toilet trainings/week | Standard Deviation 2.47 |
| Placebo | Frequency of Toilet Training in the Double-Blind Treatment Period | 5.1 toilet trainings/week | Standard Deviation 2.47 |
Secondary
Large Diameter Stools in the Double-Blind Treatment Period
Large diameter stools make defecation more difficult. Small diameter stools are better.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Large Diameter Stools in the Double-Blind Treatment Period | 1.7 large diameter stools/week | Standard Deviation 1.67 |
| Placebo | Large Diameter Stools in the Double-Blind Treatment Period | 1.7 large diameter stools/week | Standard Deviation 1.2 |
Secondary
Number of Rescue Medications Taken in the Double-Blind Treatment Period
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Number of Rescue Medications Taken in the Double-Blind Treatment Period | 1.2 rescue medications/week | Standard Deviation 1.25 |
| Placebo | Number of Rescue Medications Taken in the Double-Blind Treatment Period | 1.3 rescue medications/week | Standard Deviation 1.09 |
Secondary
Number of Retentive Posturing or Excessive Volitional Stool Retention in the Double-Blind Treatment Period
Purposefully avoiding defecation.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Number of Retentive Posturing or Excessive Volitional Stool Retention in the Double-Blind Treatment Period | 1.1 retentions/week | Standard Deviation 1.82 |
| Placebo | Number of Retentive Posturing or Excessive Volitional Stool Retention in the Double-Blind Treatment Period | 1.2 retentions/week | Standard Deviation 1.71 |
Secondary
Number of SBM Per Week in the Double-Blind Treatment Period
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Number of SBM Per Week in the Double-Blind Treatment Period | 2.3 SBM/week | Standard Deviation 2.35 |
| Placebo | Number of SBM Per Week in the Double-Blind Treatment Period | 2.1 SBM/week | Standard Deviation 1.74 |
Secondary
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.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Painful Bowel Movements Score in the Double-Blind Treatment Period | 1.3 units on a scale | Standard Deviation 1.25 |
| Placebo | Painful Bowel Movements Score in the Double-Blind Treatment Period | 1.7 units on a scale | Standard Deviation 1.34 |
Secondary
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.
Time frame: Last 4 weeks of double-blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prucalopride | 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 | 29.2 percentage of subjects |
| Placebo | 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 | 35.5 percentage of subjects |
p-value: 0.352Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Last 4 weeks of double-blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prucalopride | 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 | 43.0 percentage of subjects |
| Placebo | 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 | 43.0 percentage of subjects |
p-value: 0.5228Cochran-Mantel-Haenszel
Secondary
Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period
Time frame: 2 weeks
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Absent | 15.5 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Moderate | 19.4 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Mild | 21.4 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Severe | 27.2 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Very severe | 16.5 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Severe | 24.3 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Very severe | 24.3 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Absent | 5.6 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Mild | 18.7 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Double-Blind Treatment Period | Moderate | 27.1 percentage of subjects |
p-value: 0.1599Van Elteren test
Secondary
Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period
Time frame: 2 weeks
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Mild | 17.5 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Severe | 15.5 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Moderate | 17.5 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Very severe | 24.7 percentage of subjects |
| Prucalopride | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Absent | 24.7 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Very severe | 12.9 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Absent | 46.2 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Mild | 16.1 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Moderate | 9.7 percentage of subjects |
| Placebo | Severity of Constipation Over the Past 2 Weeks for the Final On Treatment Assessment in the Open-Label Treatment Period | Severe | 15.1 percentage of subjects |
p-value: 0.0003Van Elteren test
Secondary
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.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Stool Consistency Per SBM Score in Children With Diapers in the Double-Blind Treatment Period | 2.1 units on a scale | Standard Deviation 0.47 |
| Placebo | Stool Consistency Per SBM Score in Children With Diapers in the Double-Blind Treatment Period | 2.0 units on a scale | Standard Deviation 0.59 |
Secondary
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.
Time frame: Over the 8 week double blind treatment period
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product. Not all subjects in the Full Analysis Set had data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prucalopride | Stool Consistency Per SBM Score in Children Without Diapers in the Double-Blind Treatment Period | 3.8 units on a scale | Standard Deviation 0.96 |
| Placebo | Stool Consistency Per SBM Score in Children Without Diapers in the Double-Blind Treatment Period | 3.6 units on a scale | Standard Deviation 1.17 |
Secondary
Time to First SBM in the Double-Blind Treatment Period
After intake of the trial medication on Day 1.
Time frame: Day 1 onwards
Population: Full Analysis Set includes all subjects who were randomized and received at least 1 dose of investigational product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prucalopride | Time to First SBM in the Double-Blind Treatment Period | 67.00 hours |
| Placebo | Time to First SBM in the Double-Blind Treatment Period | 99.75 hours |
p-value: 0.377Chi-squared