Clinical Trial Results:
Phase 3, Multicenter, Randomized Study with 2 Different Doses of Prucalopride Administered to Male and Female Pediatric Subjects Aged 6 Months to 17 years with Functional Constipation, Consisting of a 12-week Double-blind, Placebo-controlled Part (Part A) to Evaluate Efficacy and Safety Followed by a 36-week Double-blind Extension Part (Part B) to Document Long-term Safety up to Week 48
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Summary
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EudraCT number |
2022-003221-22 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
13 Nov 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
26 May 2024
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First version publication date |
26 May 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TAK-555-3010
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04759833 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Avenue, Lexington, United States, MA 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Nov 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Nov 2023
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main purpose of this study is to evaluate the efficacy of prucalopride during the 12-week double-blind, placebo-controlled treatment phase and long-term (48 weeks) safety and tolerability in toilet-trained participants with functional constipation who are at least 3 years of age.
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Protection of trial subjects |
Each participant signed an informed consent form (ICF) before participating in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Jul 2021
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
9 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 175
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Worldwide total number of subjects |
175
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
1
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Children (2-11 years) |
111
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Adolescents (12-17 years) |
63
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at 42 investigative sites in the United States from 13 July 2021 to 13 November 2023. | ||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
175 participants were randomised in a 1:1:1 ratio to receive prucalopride at low/high dose/placebo in Part A of study per their body weight. All participants who completed Part A entered Part B, and those in placebo group of Part A were re-randomized based on their weight in 1:1 ratio to receive prucalopride at low/high dose in Part B of the study. | ||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Placebo-controlled Period (12 Weeks)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part A: Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing <50 kg drew equal volumes from two bottles of placebo oral solution to account for the daily dose assigned or participants weighing ≥50 kg received two placebo oral tablets, once daily (QD), during 12 weeks in Part A. Prucalopride matching placebo (oral solution or tablet) were dosed depending on the participant’s body weight (BW) at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received matching placebo of oral solution or tablet QD.
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Arm title
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Part A: Low Dose Prucalopride | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing <50 kg received 0.04 milligrams per kilogram (mg/kg) of prucalopride oral solution (drew the required volume from one bottle of 0.4 milligram per milliliter [mg/mL] and one bottle of placebo oral solution), QD or participants weighing ≥50 kg received one 2 milligram (mg) of prucalopride oral tablet and one placebo oral tablet, QD, during 12 weeks in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Prucalopride
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Investigational medicinal product code |
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Other name |
TAK-555, Prucalopride succinate
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Pharmaceutical forms |
Tablet, Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 0.04 mg/kg or 0.08 mg/kg oral solution or 2 mg oral tablet of prucalopride QD.
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Arm title
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Part A: High Dose Prucalopride | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, during 12 weeks of treatment period in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Prucalopride
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Investigational medicinal product code |
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Other name |
TAK-555, Prucalopride succinate
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Pharmaceutical forms |
Tablet, Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 0.04 mg/kg or 0.08 mg/kg oral solution or 2 mg oral tablet of prucalopride QD.
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Period 2
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Period 2 title |
Safety Extension Period (40 Weeks)
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Part B: Low Dose Prucalopride | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing <50 kg received 0.04 mg/kg of prucalopride oral solution (drew the required volume from one bottle of 0.4 mg/mL and one bottle of placebo oral solution to account for the daily dose assigned), QD or participants weighing ≥50 kg received one 2 mg of prucalopride oral tablet and one placebo oral tablet, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Prucalopride
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Investigational medicinal product code |
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Other name |
TAK-555, Prucalopride succinate
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Pharmaceutical forms |
Tablet, Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 0.04 mg/kg or 0.08 mg/kg oral solution or 2 mg oral tablet of prucalopride QD.
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Arm title
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Part B: High Dose Prucalopride | ||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Prucalopride
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Investigational medicinal product code |
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Other name |
TAK-555, Prucalopride succinate
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Pharmaceutical forms |
Tablet, Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received 0.04 mg/kg or 0.08 mg/kg oral solution or 2 mg oral tablet of prucalopride QD.
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Baseline characteristics reporting groups
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Reporting group title |
Part A: Placebo
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Reporting group description |
Participants weighing <50 kg drew equal volumes from two bottles of placebo oral solution to account for the daily dose assigned or participants weighing ≥50 kg received two placebo oral tablets, once daily (QD), during 12 weeks in Part A. Prucalopride matching placebo (oral solution or tablet) were dosed depending on the participant’s body weight (BW) at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A: Low Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.04 milligrams per kilogram (mg/kg) of prucalopride oral solution (drew the required volume from one bottle of 0.4 milligram per milliliter [mg/mL] and one bottle of placebo oral solution), QD or participants weighing ≥50 kg received one 2 milligram (mg) of prucalopride oral tablet and one placebo oral tablet, QD, during 12 weeks in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A: High Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, during 12 weeks of treatment period in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Part A: Placebo
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Reporting group description |
Participants weighing <50 kg drew equal volumes from two bottles of placebo oral solution to account for the daily dose assigned or participants weighing ≥50 kg received two placebo oral tablets, once daily (QD), during 12 weeks in Part A. Prucalopride matching placebo (oral solution or tablet) were dosed depending on the participant’s body weight (BW) at the randomization visit. | ||
Reporting group title |
Part A: Low Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.04 milligrams per kilogram (mg/kg) of prucalopride oral solution (drew the required volume from one bottle of 0.4 milligram per milliliter [mg/mL] and one bottle of placebo oral solution), QD or participants weighing ≥50 kg received one 2 milligram (mg) of prucalopride oral tablet and one placebo oral tablet, QD, during 12 weeks in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||
Reporting group title |
Part A: High Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, during 12 weeks of treatment period in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||
Reporting group title |
Part B: Low Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.04 mg/kg of prucalopride oral solution (drew the required volume from one bottle of 0.4 mg/mL and one bottle of placebo oral solution to account for the daily dose assigned), QD or participants weighing ≥50 kg received one 2 mg of prucalopride oral tablet and one placebo oral tablet, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||
Reporting group title |
Part B: High Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||
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End point title |
Parts A and B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [1] | ||||||||||||||||||||||||||||||
End point description |
Adverse event (AE) = any untoward medical occurrence in clinical investigation participant administered pharmaceutical product that did not necessarily have causal relationship with this treatment. TEAE = any event emerging/manifesting at/after initiation of treatment with investigational product (IP)/medicinal product/any existing event that worsens in either intensity/frequency following exposure to IP/medicinal product. Serious adverse event (SAE) = any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability/incapacity, is congenital abnormality/birth defect, is important medical event. For Part A, Safety Analysis Set included all participants who received at least 1 dose of study drug in Part A. For Part B, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part B.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to Week 52
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this end point as they were not performed due to study termination based on futility. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Part A: Change from Baseline in Average Number of Weekly Number of Spontaneous Bowel Movements (SBMs) at Week 12 [2] | ||||||||||||||||
End point description |
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. The Completers Analysis Set included all toilet-trained participants who were at least 3 years of age in the Modified Intent-to-treat Analysis Set (mITT) analysis set who had an average number of SBM available for all 12 weeks in the placebo-controlled part (Part A) of the study.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this end point as they were not performed due to study termination based on futility. |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities [3] | ||||||||||||||||||
End point description |
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. For Part A, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part A. For Part B, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part B.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to Week 52
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this end point as they were not performed due to study termination based on futility. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Parts A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters [4] | ||||||||||||||||||
End point description |
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. For Part A, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part A. For Part B, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part B.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to Week 52
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this end point as they were not performed due to study termination based on futility. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Parts A and B: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [5] | ||||||||||||||||||
End point description |
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. For Part A, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part A. For Part B, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part B.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to Week 52
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this end point as they were not performed due to study termination based on futility. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Part A: Change From Baseline in Participants’ Weekly Stool Consistency Based on Bristol Stool Form Scale (BSFS) Score at Week 12 Categorized by Age | ||||||||||||||||||||||||
End point description |
BSFS 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=constipation while a score of 6 or 7=diarrhea. A better score (scores of 3 and 4 represent ideal stools as they are easy to defecate while not containing excess liquid, 5 indicates average consistency but lack of dietary fiber) would trend toward the middle of the scale(3 to 5). Daily scores were summed to obtain a weekly score ranging from 7 to 49 with higher scores indicating diarrhea. Data for this outcome measure is reported per age group bifurcation.mITT Analysis Set=all randomised participants who received at least 1 dose of study drug in Part A. Number of subjects analysed=participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Part A: Change From Baseline in Weekly Straining Score Based on a 3-point Likert Scale at Week 12 | ||||||||||||||||||||
End point description |
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. The mITT Analysis Set included all randomised participants who received at least 1 dose of the study drug in Part A. Number of subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Part A: Percentage of Responders Based on Assessment of SBMs | ||||||||||||||||
End point description |
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. The mITT Analysis Set included all randomised participants who received at least 1 dose of the study drug in Part A. Number of subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Baseline through Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Part A: Percentage of Participants With Fecal Incontinence at Week 12 | ||||||||||||||||
End point description |
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 the nearest single decimal place. The mITT Analysis Set included all randomised participants who received at least 1 dose of the study drug in Part A. Number of subjects analysed is the number of participants with data available for analyses.
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End point type |
Secondary
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End point timeframe |
Week 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride [6] | ||||||||||||||||||||||||
End point description |
The PK analysis set included all participants regardless of age in the safety analysis sets for whom at least 1 PK sample was evaluable. Number of subjects analysed is the number of participants with data available for analyses. 'n' signifies the number of participants with data available for analyses at the specified time point.
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End point type |
Other pre-specified
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End point timeframe |
1 to 3 hours post-dose at Baseline (Day 0), 14 to 26 hours post-dose at Weeks 4, 8 and 12
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Descriptive pharmacokinetic data was collected and analysed for prucalopride arms only. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first dose of study drug up to Week 52
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Adverse event reporting additional description |
For Part A, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part A. For Part B, the Safety Analysis Set included all participants who received at least 1 dose of study drug in Part B.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26
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Reporting groups
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Reporting group title |
Part A: Low Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.04 mg/kg of prucalopride oral solution (drew the required volume from one bottle of 0.4 mg/mL and one bottle of placebo oral solution), QD or participants weighing ≥50 kg received one 2 mg of prucalopride oral tablet and one placebo oral tablet, QD, during 12 weeks in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A: High Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, during 12 weeks of treatment period in Part A. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part A: Placebo
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Reporting group description |
Participants weighing <50 kg drew equal volumes from two bottles of placebo oral solution to account for the daily dose assigned or participants weighing ≥50 kg received two placebo oral tablets, QD, during 12 weeks in Part A. Prucalopride matching placebo (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B: High Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.08 mg/kg of prucalopride oral solution (drew the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg received two 2 mg of prucalopride oral tablets, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part B: Low Dose Prucalopride
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Reporting group description |
Participants weighing <50 kg received 0.04 mg/kg of prucalopride oral solution (drew the required volume from one bottle of 0.4 mg/mL and one bottle of placebo oral solution to account for the daily dose assigned), QD or participants weighing ≥50 kg received one 2 mg of prucalopride oral tablet and one placebo oral tablet, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) were dosed depending on the participant’s BW at the randomization visit. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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17 Dec 2020 |
The following changes were made as per Amendment 1: 1) Clarified that the primary endpoint was based on data collected during the placebo-controlled part (Part A). 2) Corrected text describing Part B of the study as placebo-controlled. 3) Corrected the population used for the primary estimand of interest from Intent-to-Treat (ITT) to mITT. 4) Corrected the number of bowel movements (BMs) from greater than (>)3 to ≥3. |
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20 Oct 2021 |
The following changes were made as per Amendment 2: 1) Added that if a participant weighing ≥50 kg could not tolerate the tablets, they could be switched to oral solution for the duration of study participation. Further, switching from oral solution to tablets was not allowed. 2) Revised the frequency for providing rescue medications to align with operational processes. 3) Aligned the screening visit window with wording in the protocol. 4) Added patient global impression of severity (PGI-S) and caregiver global impression of severity (CGI-S) assessments at screening. 5) Specified that if a participant chose to withdraw from study participation due to personal concerns or unavoidable circumstances related to the coronavirus disease 2019 (COVID-19) pandemic (other than a COVID-19–related AE), this had to be specified as the reason for participant withdrawal in the electronic case report form (eCRF). 6) Added details on the anchor-based analysis. 7) Added details of COVID-19-related flexibility in study conduct. |
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27 Oct 2022 |
The following changes were made as per Amendment 3: 1) Updated the exploratory endpoints on “proportion of participants with an average of ≥3 (S)BMs per week and increase of ≥1 (S)BM compared to baseline during a 12-week double-blind, placebo-controlled treatment phase” and “proportion of participants with an average of ≤1 (S)BMs per week during the 12-week double-blind, placebo-controlled treatment phase” to only evaluate SBMs, not BMs. 2) Updated the duration of the study from approximately 60 to approximately 52 months (or from 3-4 to 4-4.5 years of age). 3) Corrected the duration of the screening period from approximately 21 - 33 days (and maximum duration of participation, where mentioned, from 55 - 56 weeks). 4) Added a reminder to check whether the participant had experienced any psychiatric changes throughout the study. 5) Corrected to indicate that restrictions related to lifestyle modifications (including dietary changes) were applicable from randomization onwards and to include the specification that study-allowed rescue medication was not restricted. 6) Added a new section describing what actions should be taken in case of suicidal ideation (SI)/suicidal behavior (SIB). |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
