Trial Outcomes & Findings for A Study of Prucalopride For Functional Constipation in Children and Teenagers (NCT NCT04759833)

Last Updated: 2024-06-06

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

175 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2024-06-06

Participant Flow

Participants took part in the study at 42 investigative sites in the United States from 13 July 2021 to 13 November 2023.

A total of 175 participants with a diagnosis of functional constipation were enrolled and randomized in a 1:1:1 ratio to receive either prucalopride at low dose, high dose, or matching placebo in Part A of the study depending on their body weight. All participants who completed Part A entered Part B, and those in the placebo group of Part A were re-randomized based on their weight in a 1:1 ratio to receive either prucalopride at a low or high dose in Part B of the study.

Participant milestones

Participant milestones
Measure	Part A: Placebo Participants weighing \<50 kilograms (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.	Part A: Low Dose Prucalopride 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.	Part A: High Dose Prucalopride 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
PartA:Placebo-controlled Period(12Weeks) STARTED	56	60	59	0	0
PartA:Placebo-controlled Period(12Weeks) COMPLETED	46	49	39	0	0
PartA:Placebo-controlled Period(12Weeks) NOT COMPLETED	10	11	20	0	0
Part B:Safety Extension Period(40 Weeks) STARTED	0	0	0	72	62
Part B:Safety Extension Period(40 Weeks) COMPLETED	0	0	0	37	28
Part B:Safety Extension Period(40 Weeks) NOT COMPLETED	0	0	0	35	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Placebo Participants weighing \<50 kilograms (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.	Part A: Low Dose Prucalopride 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.	Part A: High Dose Prucalopride 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
PartA:Placebo-controlled Period(12Weeks) Adverse Event	1	4	2	0	0
PartA:Placebo-controlled Period(12Weeks) Lack of Efficacy	0	0	1	0	0
PartA:Placebo-controlled Period(12Weeks) Lost to Follow-up	4	1	4	0	0
PartA:Placebo-controlled Period(12Weeks) Study Terminated by Sponsor	0	2	3	0	0
PartA:Placebo-controlled Period(12Weeks) Withdrawal of Consent by Participant	5	3	9	0	0
PartA:Placebo-controlled Period(12Weeks) Noncompliance with Study Drug	0	0	1	0	0
PartA:Placebo-controlled Period(12Weeks) Physician Decision	0	1	0	0	0
Part B:Safety Extension Period(40 Weeks) Adverse Event	0	0	0	1	1
Part B:Safety Extension Period(40 Weeks) Lack of Efficacy	0	0	0	0	1
Part B:Safety Extension Period(40 Weeks) Lost to Follow-up	0	0	0	1	3
Part B:Safety Extension Period(40 Weeks) Study Terminated by Sponsor	0	0	0	21	16
Part B:Safety Extension Period(40 Weeks) Withdrawal of Consent by Participant	0	0	0	4	8
Part B:Safety Extension Period(40 Weeks) Reason not Specified	0	0	0	8	5

Baseline Characteristics

A Study of Prucalopride For Functional Constipation in Children and Teenagers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Placebo n=56 Participants 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.	Part A: Low Dose Prucalopride n=60 Participants 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.	Part A: High Dose Prucalopride n=59 Participants 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.	Total n=175 Participants Total of all reporting groups
Age, Continuous	9.4 years STANDARD_DEVIATION 3.73 • n=5 Participants	9.8 years STANDARD_DEVIATION 4.00 • n=7 Participants	9.8 years STANDARD_DEVIATION 3.96 • n=5 Participants	9.7 years STANDARD_DEVIATION 3.88 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	28 Participants n=7 Participants	28 Participants n=5 Participants	91 Participants n=4 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	32 Participants n=7 Participants	31 Participants n=5 Participants	84 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=5 Participants	28 Participants n=7 Participants	30 Participants n=5 Participants	81 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	32 Participants n=7 Participants	29 Participants n=5 Participants	94 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	68 Participants n=4 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	34 Participants n=7 Participants	35 Participants n=5 Participants	100 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	56 Participants n=5 Participants	60 Participants n=7 Participants	59 Participants n=5 Participants	175 Participants n=4 Participants
Weight	44.24 kg STANDARD_DEVIATION 25.318 • n=5 Participants	47.24 kg STANDARD_DEVIATION 24.326 • n=7 Participants	43.72 kg STANDARD_DEVIATION 23.793 • n=5 Participants	45.10 kg STANDARD_DEVIATION 24.381 • n=4 Participants
Height	139.86 centimeter (cm) STANDARD_DEVIATION 23.563 • n=5 Participants	142.57 centimeter (cm) STANDARD_DEVIATION 22.480 • n=7 Participants	140.35 centimeter (cm) STANDARD_DEVIATION 24.554 • n=5 Participants	140.96 centimeter (cm) STANDARD_DEVIATION 23.435 • n=4 Participants
Body Mass Index (BMI)	20.76 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 6.702 • n=5 Participants	21.63 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 6.461 • n=7 Participants	20.44 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 6.255 • n=5 Participants	20.95 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 6.454 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=20 Participants 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.	Part A: Low Dose Prucalopride n=18 Participants 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.	Part A: High Dose Prucalopride n=11 Participants 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
Part A: Change From Baseline in Average Number of Weekly Number of Spontaneous Bowel Movements (SBMs) at Week 12	1.4 SBMs per week Standard Deviation 1.90	1.9 SBMs per week Standard Deviation 2.67	0.9 SBMs per week Standard Deviation 1.44	—	—

PRIMARY outcome

Timeframe: From first dose of study drug up to Week 52

Population: 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.

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 investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, is an important medical event.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=56 Participants 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.	Part A: Low Dose Prucalopride n=60 Participants 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.	Part A: High Dose Prucalopride n=59 Participants 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.	Part B: Low Dose Prucalopride n=72 Participants 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.	Part B: High Dose Prucalopride n=62 Participants 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.
Parts A and B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TEAEs	15 Participants	24 Participants	18 Participants	22 Participants	17 Participants
Parts A and B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) TESAEs	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=56 Participants 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.	Part A: Low Dose Prucalopride n=60 Participants 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.	Part A: High Dose Prucalopride n=59 Participants 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.	Part B: Low Dose Prucalopride n=72 Participants 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.	Part B: High Dose Prucalopride n=62 Participants 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.
Parts A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=56 Participants 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.	Part A: Low Dose Prucalopride n=60 Participants 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.	Part A: High Dose Prucalopride n=59 Participants 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.	Part B: Low Dose Prucalopride n=72 Participants 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.	Part B: High Dose Prucalopride n=62 Participants 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.
Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=56 Participants 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.	Part A: Low Dose Prucalopride n=60 Participants 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.	Part A: High Dose Prucalopride n=59 Participants 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.	Part B: Low Dose Prucalopride n=72 Participants 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.	Part B: High Dose Prucalopride n=62 Participants 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.
Parts A and B: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: The mITT Analysis Set included all randomized participants who received at least 1 dose of the study drug in Part A. Overall number analyzed is the number of participants with data available for analyses.

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 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=37 Participants 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.	Part A: Low Dose Prucalopride n=40 Participants 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.	Part A: High Dose Prucalopride n=34 Participants 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
Part A: Change From Baseline in Participants' Weekly Stool Consistency Based on Bristol Stool Form Scale (BSFS) Score at Week 12 Categorized by Age Participants <8 Years	-0.1 score on a scale Standard Deviation 16.56	9.8 score on a scale Standard Deviation 12.75	7.1 score on a scale Standard Deviation 6.31	—	—
Part A: Change From Baseline in Participants' Weekly Stool Consistency Based on Bristol Stool Form Scale (BSFS) Score at Week 12 Categorized by Age Participants ≥8 Years	12.6 score on a scale Standard Deviation 16.77	13.1 score on a scale Standard Deviation 21.15	7.0 score on a scale Standard Deviation 10.44	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=37 Participants 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.	Part A: Low Dose Prucalopride n=40 Participants 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.	Part A: High Dose Prucalopride n=34 Participants 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
Part A: Change From Baseline in Weekly Straining Score Based on a 3-point Likert Scale at Week 12	-5.7 score on a scale Standard Deviation 8.49	-5.2 score on a scale Standard Deviation 5.92	-7.6 score on a scale Standard Deviation 5.12	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=52 Participants 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.	Part A: Low Dose Prucalopride n=56 Participants 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.	Part A: High Dose Prucalopride n=55 Participants 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
Part A: Percentage of Responders Based on Assessment of SBMs	1.9 percentage of responders Interval 0.0 to 0.0	3.6 percentage of responders Interval 0.0 to 0.0	0 percentage of responders Interval 0.0 to 0.0	—	—

SECONDARY outcome

Timeframe: 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 the nearest single decimal place.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=31 Participants 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.	Part A: Low Dose Prucalopride n=33 Participants 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.	Part A: High Dose Prucalopride n=30 Participants 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
Part A: Percentage of Participants With Fecal Incontinence at Week 12	12.9 percentage of participants Interval 0.0 to 0.0	3.0 percentage of participants Interval 0.0 to 0.0	16.7 percentage of participants Interval 0.0 to 0.0	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 1-3 hours post-dose at Baseline (Day 0), 14-26 hours post-dose at Weeks 4, 8 and 12

Population: The PK analysis set included all participants regardless of age in the safety analysis sets for whom at least 1 PK sample was evaluable. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified time point.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=8 Participants 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.	Part A: Low Dose Prucalopride n=12 Participants 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.	Part A: High Dose Prucalopride 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.	Part B: Low Dose Prucalopride 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.	Part B: High Dose Prucalopride 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.
Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride Week 4, 14-26 hours	2.607 nanograms per milliliter (ng/mL) Standard Deviation 0.7336	3.693 nanograms per milliliter (ng/mL) Standard Deviation 2.0613	—	—	—
Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride Week 8, 14-26 hours	2.343 nanograms per milliliter (ng/mL) Standard Deviation 1.8725	2.963 nanograms per milliliter (ng/mL) Standard Deviation 2.0794	—	—	—
Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride Week 12, 14-26 hours	4.365 nanograms per milliliter (ng/mL) Standard Deviation 3.6288	3.001 nanograms per milliliter (ng/mL) Standard Deviation 4.5358	—	—	—
Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride Baseline (Day 0), 1-3 hours	4.707 nanograms per milliliter (ng/mL) Standard Deviation 3.4659	5.903 nanograms per milliliter (ng/mL) Standard Deviation 4.0231	—	—	—

Adverse Events

Part A: Placebo

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Part A: Low Dose Prucalopride

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Part A: High Dose Prucalopride

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Part B: Low Dose Prucalopride

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Part B: High Dose Prucalopride

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Placebo n=56 participants at risk 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.	Part A: Low Dose Prucalopride n=60 participants at risk 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.	Part A: High Dose Prucalopride n=59 participants at risk 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.	Part B: Low Dose Prucalopride n=72 participants at risk 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.	Part B: High Dose Prucalopride n=62 participants at risk 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/56 • From first dose of study drug up to Week 52 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.	0.00% 0/60 • From first dose of study drug up to Week 52 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.	0.00% 0/59 • From first dose of study drug up to Week 52 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.	0.00% 0/72 • From first dose of study drug up to Week 52 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.	1.6% 1/62 • From first dose of study drug up to Week 52 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.
Psychiatric disorders Depression	1.8% 1/56 • From first dose of study drug up to Week 52 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.	0.00% 0/60 • From first dose of study drug up to Week 52 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.	0.00% 0/59 • From first dose of study drug up to Week 52 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.	0.00% 0/72 • From first dose of study drug up to Week 52 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.	0.00% 0/62 • From first dose of study drug up to Week 52 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.
Psychiatric disorders Intentional self-injury	0.00% 0/56 • From first dose of study drug up to Week 52 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.	0.00% 0/60 • From first dose of study drug up to Week 52 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.	0.00% 0/59 • From first dose of study drug up to Week 52 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.	1.4% 1/72 • From first dose of study drug up to Week 52 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.	0.00% 0/62 • From first dose of study drug up to Week 52 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.
Psychiatric disorders Suicidal ideation	0.00% 0/56 • From first dose of study drug up to Week 52 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.	0.00% 0/60 • From first dose of study drug up to Week 52 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.	0.00% 0/59 • From first dose of study drug up to Week 52 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.	1.4% 1/72 • From first dose of study drug up to Week 52 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.	0.00% 0/62 • From first dose of study drug up to Week 52 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.

Other adverse events

Other adverse events
Measure	Part A: Placebo n=56 participants at risk 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.	Part A: Low Dose Prucalopride n=60 participants at risk 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.	Part A: High Dose Prucalopride n=59 participants at risk 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.	Part B: Low Dose Prucalopride n=72 participants at risk 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.	Part B: High Dose Prucalopride n=62 participants at risk 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.
Nervous system disorders Headache	5.4% 3/56 • From first dose of study drug up to Week 52 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.	13.3% 8/60 • From first dose of study drug up to Week 52 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.	8.5% 5/59 • From first dose of study drug up to Week 52 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.	4.2% 3/72 • From first dose of study drug up to Week 52 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.	8.1% 5/62 • From first dose of study drug up to Week 52 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.
Infections and infestations Nasopharyngitis	1.8% 1/56 • From first dose of study drug up to Week 52 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.	5.0% 3/60 • From first dose of study drug up to Week 52 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.	1.7% 1/59 • From first dose of study drug up to Week 52 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.	9.7% 7/72 • From first dose of study drug up to Week 52 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.	1.6% 1/62 • From first dose of study drug up to Week 52 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.
Gastrointestinal disorders Vomiting	3.6% 2/56 • From first dose of study drug up to Week 52 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.	13.3% 8/60 • From first dose of study drug up to Week 52 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.	6.8% 4/59 • From first dose of study drug up to Week 52 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.	0.00% 0/72 • From first dose of study drug up to Week 52 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.	3.2% 2/62 • From first dose of study drug up to Week 52 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.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER