ConstipationPhase 3NCT04759833
A Study of Prucalopride For Functional Constipation in Children and Teenagers
A Phase 3 study testing Prucalopride in people with Constipation, run by Takeda at 41 sites in United States.
Trial summary
Functional constipation is a condition when it is very hard to pass a stool that is not due to any other health problem or to medicines being taken. This condition is more common in children and teenagers. Read more about this study
- Who is it for?
- Ages 6 months to 17 years
- Conditions the study is for
- Constipation
- What is being tested?
- Prucalopride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 175 participants
- Where
- 41 sitesUnited States
- Study dates
- 13 Jul 2021to 13 Nov 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants and/or their parent(s)/caregiver(s)/legally authorized representative(s) have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Ability to voluntarily provide written, signed, and dated (personally or via parent[s]/caregiver[s]/legally authorized representative[s]) informed consent/assent as applicable to participate in the study.
- Note: Participants and/or parent(s)/caregiver(s)/legally authorized representative(s) (where appropriate depending on age and local regulation) can also provide consent/assent to the sparse Pharmacokinetic (PK) sampling in this study.
- Toilet-trained participants 3 years to 17 years of age, inclusive, or non-toilet-trained participants 6 months to 17 years of age, inclusive.
- Participant weighs greater than or equal to (>=) 5.5 kilograms (kg) (12 pounds [lbs]).
- Male, or non-pregnant, non-lactating female participants who are sexually active and agree to comply with the applicable contraceptive requirements of the protocol or females of non-childbearing potential.
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- Note: All female participants >= 12 years and/or female participants lesser than (<) 12 years who have started menarche must have a negative serum pregnancy test at screening.
- Participant meets modified Rome IV criteria:
- For child/adolescent (aged > 4 years) functional constipation (H3a):
- Participants must have lesser than or equal to (<=) 2 defecations per week and 1 or more of the following occurring at least once per week for a minimum of 1 month:
- >= 1 episode of fecal incontinence per week (only for participants after the acquisition of toileting skills).
- History of retentive posturing or excessive volitional stool retention.
- History of painful or hard bowel movements (BMs).
- Presence of large fecal mass in rectum.
- History of large diameter stools which can obstruct the toilet. In addition, the participant does not satisfy sufficient criteria for a diagnosis of irritable bowel syndrome (IBS) and, after appropriate evaluation, the participants symptoms cannot be fully explained by another medical condition.
- For infants/toddler (aged 6 months to <= 4 years) functional constipation (G7):
- Participants must have <= 2 defecations per week and >= 1 month of at least 1 of the following:
- History of excessive stool retention
- History of painful or hard BMs
- History of large-diameter stools (in the diaper)
- Presence of a large fecal mass in the rectum
- In toilet-trained children, the following additional criteria may be used:
- At least 1 episode/week of incontinence after the acquisition of toileting skills
- History of large-diameter stools which may obstruct the toilet - Participant and/or parent(s)/caregiver(s)/legally authorized representative(s) is willing to discontinue any laxatives during the screening period up to disimpaction and agrees to adhere to the protocol-specified disimpaction and rescue medication rules, if applicable.
- To be evaluated prior to randomization:
- Participant has an average of < 3 SBMs (defecations) per week during the screening period and prior to the disimpaction.
- Participant or legally authorized representative (dependent on participant age) is compliant with completing the electronic diary for at least 7 consecutive days preceding the disimpaction.
Who cannot join
- Current or recurrent disease that could affect the action, absorption, or disposition of the investigational product (IP), or clinical or laboratory assessments.
- Any clinically significant abnormal findings on the electrocardiogram (ECG) that indicates a dysrhythmia or conduction abnormalities (such as abnormal heart rate, PR, QRS, or QT).
- Major cardiovascular disease such as: cardiomyopathy, cardiac insufficiency, uncorrected congenital heart disease, symptomatic valve disorders, or septal defects.
- Current or relevant history of physical or psychiatric illness (e.g. severe autism, depression, etc.), any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the IP or procedures.
- Non-retentive fecal incontinence.
- Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum.
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- Current use of any medication (including over-the-counter, herbal, or homeopathic preparations) that could affect (improve or worsen) the condition being studied (e.g. opioids), or could affect the action, absorption, or disposition of the IP, or clinical or laboratory assessment. (Current use is defined as use within the past 5 days).
- Participants with renal impairment:
- Participants <= 2 years of age with serum creatinine greater than normal (screening sample results using central laboratory pediatric reference ranges).
- Participants > 2 years of age with severe renal impairment or end stage renal disease (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m^2).
- Known or suspected intolerance or hypersensitivity to the IP(s), closely-related compounds, or any of the stated ingredients.
- Known history of alcohol or other substance abuse within the last year.
- Within 30 days prior to the first dose of the IP in the current study:
- Have used any IP.
- Have been enrolled in a clinical study (including vaccine studies) that may or may not include the administration of an IP that, in the investigator's opinion, may impact this study.
- Participant used prucalopride within 10 days prior to the first dose of the IP or has been unsuccessfully treated with prucalopride before.
- Participant meets Rome IV criteria for other Child/Adolescent Functional Gastrointestinal Disorders (FGID) (H1 - H2 and H3b).
- Participant with secondary causes of constipation:
- Endocrine disorders (e.g., hypopituitarism, hypothyroidism, hypercalcemia, pheochromocytoma, glucagon-producing tumors) unless these are controlled by appropriate medical therapy. Participant with uncontrolled diabetes mellitus is to be excluded
- Metabolic disorders (e.g. porphyria, uremia, hypokalemia, hypothyroidism, amyloid neuropathy), unless controlled by appropriate medical therapy
- Neurological disorders (e.g. cerebral tumors, cerebrovascular accidents, multiple sclerosis, meningocele, aganglionosis, hypoganglionosis, hyperganglionosis, autonomic neuropathy, spinal cord injury, Chagas disease
- Organic disorders (known or suspected) of the large bowel (e.g. obstruction from any cause including biliary obstruction, malignancy, intestinal perforation, obstructive ileus, pseudo-obstruction, history of or current anorectal malformations, severe inflammation of the intestinal tract, such as Crohn's disease, ulcerative colitis or toxic megacolon/megarectum, Hirschsprung's disease)
- Celiac disease, cow milk allergy
- Surgery: history of gastrointestinal surgery related or possibly related to the presence of constipation
- Lactose intolerance
- Any of the following clinically significant abnormalities of serum biochemistry:
- Serum aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN) at screening.
- Serum alanine aminotransferase (ALT) >1.5 times ULN at screening.
- Total bilirubin outside the age-adjusted normal range, except for participants with Gilbert's syndrome.
- Any significant underlying liver disease.
- Participant is not able to swallow the IP (liquid or tablet).
- Participant is pregnant or planning to get pregnant during study period.
- To be evaluated prior to randomization:
- Participant has used other disimpaction medication in lieu of the protocol-provided medication.
- Participant has used non-protocol approved medications to induce BMs during the screening period or disimpaction.
- The participant has failed the disimpaction based on the investigator's assessment.
- Worsening of depression and emergence of suicidal thoughts.
Trial locations and contacts
41 sites in 1 country.
41 sites in 1 country
United States41 sites
Advanced Research Center, Inc.
Anaheim, California, 92805
University of Colorado Denver
Aurora, Colorado, 80045
Tekton Research, Inc.
Beaumont, Texas, 77706
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
The University of Chicago Medical Center
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
Cedar Health Research
Dallas, Texas, 75251
Pediatric Specialist of Virginia
Fairfax, Virginia, 22031
Allure Health LLC
Friendswood, Texas, 77546
Cyn3rgy Research & Development
Gresham, Oregon, 97030
Direct Helpers Research Center
Hialeah, Florida, 33012
Texas Children's Hospital
Houston, Texas, 77030
Pediatric Associates
Houston, Texas, 77087
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
Pediatric & Adult Research Center
Kissimmee, Florida, 34741
GI For Kids
Knoxville, Tennessee, 37922
Auzmer Research
Lakeland, Florida, 33813
Le Bonheur Children's Hospital
Memphis, Tennessee, 38105
University of Miami - Miller School of Medicine
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Florida Research Center, Inc.
Miami, Florida, 33174
Jersey Shore University Medical Center
Neptune City, New Jersey, 07753
CUMC Pediatrics-GI
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
Orlando Health - APH Center for Digestive Health and Nutrition
Orlando, Florida, 32806
GI Pediatric Subspecialty Clinic
Peoria, Illinois, 61603
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health & Science University
Portland, Oregon, 97239
Pediatric Center
Richmond, Texas, 77469
University of California, Davis Department of Pediatrics
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84108
University of California
San Francisco, California, 94158
Willis-Knighton Center for Pediatric Gastroenterology & Advanced Endoscopy
Shreveport, Louisiana, 71118
Baystate Health
Springfield, Massachusetts, 01199
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Novak Clinical Research
Tucson, Arizona, 85741
Eclipse Clinical Research
Tucson, Arizona, 85745
Medstar Georgetown University Hospital
Washington D.C., District of Columbia, 20016
About this study
Official title: 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
Functional constipation is a condition when it is very hard to pass a stool that is not due to any other health problem or to medicines being taken. This condition is more common in children and teenagers.
This study has 2 parts:
Read more
The main aim of the 1st part of the study is to learn if a medicine called prucalopride can improve bowel movements in children and teenagers with functional constipation. Another aim is to check for side effects from 2 different doses of prucalopride. The main aim of the 2nd part of the study is to continue to check for side effects from 2 different doses of prucalopride.
In the 1st part, at the first visit, the study doctor will check who can take part. Participants who take part will be picked for 1 of 3 treatments by chance.
- A low dose of prucalopride once a day.
- A higher dose of prucalopride once a day.
- A placebo once a day. In this study, a placebo will look like prucalopride but will not have any medicine in it. Participants will be treated with prucalopride or a placebo for 12 weeks.
Participants who took prucalopride will continue to the 2nd part of the study. They will have the same treatment as they did in the 1st part of the study. They will continue with their treatment for another 36 weeks. Participants who took placebo in the 1st part of the study will receive prucalopride in the 2nd part of the study. They will be picked for a low dose or a high dose of prucalopride by chance.
Participants will visit the clinic a few times during treatment. The clinic staff will also telephone the participants, or their parents or caregivers throughout treatment for a check-up 4 weeks after last treatment, the clinic staff will telephone the participants, or their parents or caregivers for a final check-up.
Read the detailed description
This study consists of a 12-week double-blind, placebo-controlled part (Part A) followed by a 36-week double-blind safety extension part (Part B). Participants aged 3 to 17 years are planned for randomization in a 1:1:1 ratio to the Low Dose Group, High Dose Group, or matching placebo (placebo-controlled part [Part A]). After completion of Part A, participants in the placebo group will be re-randomized in a 1:1 ratio to the Low Dose Group or the High Dose Group (safety extension part [Part B]). Randomization at study entry will be stratified by toilet-trained status.
- Conditions
- Constipation
- Being tested
- Prucalopride, Placebo
- Medical subject headings
- Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrucaloprideDrug
Also called TAK-555, Prucalopride succinate
Prucalopride oral solution or oral tablets.
PlaceboOther
Prucalopride-matching placebo oral solution or oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Placebo | Placebo comparator | Participants weighing <50 kilograms (kg) will draw equal volumes from two bottles of placebo oral solution to account for the daily dose assigned or participants weighing ≥ 50 kg will receive two placebo oral tablets, once daily (QD), during 12 weeks in Part A. Prucalopride matching placebo (oral solution or tablet) will be dosed depending on the participant's body weight (BW) at the randomization visit. Receives: Other: Placebo |
| Part A: Low Dose Prucalopride | Experimental | Participants weighing <50 kg will receive 0.04 milligrams per kilogram (mg/kg) of prucalopride oral solution (will draw 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 will receive 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) will be dosed depending on the participant's BW at the randomization visit. Receives: Drug: Prucalopride |
| Part A: High Dose Prucalopride | Experimental | Participants weighing <50 kg will receive 0.08 mg/kg of prucalopride oral solution (will draw the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg will receive two 2 mg of prucalopride oral tablets, QD, during 12 weeks of treatment period in Part A. Prucalopride (oral solution or tablet) will be dosed depending on the participant's BW at the randomization visit. Receives: Drug: Prucalopride |
| Part B: Low Dose Prucalopride | Experimental | Participants weighing <50 kg will receive 0.04 mg/kg of prucalopride oral solution (will draw 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 will receive 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) will be dosed depending on the participant's BW at the randomization visit. Receives: Drug: Prucalopride |
| Part B: High Dose Prucalopride | Experimental | Participants weighing <50 kg will receive 0.08 mg/kg of prucalopride oral solution (will draw the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg will receive two 2 mg of prucalopride oral tablets, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) will be dosed depending on the participant's BW at the randomization visit. Receives: Drug: Prucalopride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Change From Baseline in Average Number of Weekly Number of Spontaneous Bowel Movements (SBMs) at Week 12
Spontaneous bowel movement was defined as a bowel movement that was not preceded within a period of 24 hours by the intake of rescue medication. The average change from baseline in number of SBMs per week derived from the (e-diary) data, in toilet-trained participants who were at least 3 years of age collected during the placebo-controlled part (Part A) was assessed.
Measured: Baseline, Week 12
Parts A and B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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.
Measured: From first dose of study drug up to Week 52
Parts A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters
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.
Measured: From first dose of study drug up to Week 52
Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities
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.
Measured: From first dose of study drug up to Week 52
Parts A and B: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
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.
Measured: From first dose of study drug up to Week 52
Secondary outcomes (4)
Part A: Change From Baseline in Participants' Weekly Stool Consistency Based on Bristol Stool Form Scale (BSFS) Score at Week 12 Categorized by Age
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.
Measured: Baseline, Week 12
Part A: Change From Baseline in Weekly Straining Score Based on a 3-point Likert Scale at 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.
Measured: Baseline, Week 12
Part A: Percentage of Responders Based on Assessment of SBMs
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.
Measured: Baseline through Week 12
Part A: Percentage of Participants With Fecal Incontinence at 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.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start13 Jul 2021
- Primary completion13 Nov 2023
- Study completion13 Nov 2023
Why it stopped: Data Monitoring Committee (DMC) decision; terminated due to futility, with no safety concerns; FDA agreement to terminate the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ConstipationStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04759833
- Sponsor's protocol ID
- TAK-555-3010
- Other IDs
- 2022-003221-22
- Status last verified
- May 2024
- First submitted
- 16 Feb 2021
- Last updated
- 6 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Cuffari C, Spalding W, Achenbach H, Thakur M, Gabriel A. Design of a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of prucalopride in pediatric patients with functional constipation. Contemp Clin Trials Commun. 2023 Apr 30;33:101144. doi: 10.1016/j.conctc.2023.101144. eCollection 2023 Jun.
PubMed 37215389
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04759833
- Acronym / sponsor ID
- TAK-555-3010
- Conditions
- Constipation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data Monitoring Committee (DMC) decision; terminated due to futility, with no safety concerns; FDA agreement to terminate the study.
- Enrolment
- 175 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 13 Jul 2021 (actual)
- Primary completion
- 13 Nov 2023 (actual)
- Study completion
- 13 Nov 2023 (actual)
- First posted
- 18 Feb 2021 (actual)
- Results
- Posted 6 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Functional constipation is a condition when it is very hard to pass a stool that is not due to any other health problem or to medicines being taken. This condition is more common in children and teenagers.
This study has 2 parts:
The main aim of the 1st part of the study is to learn if a medicine called prucalopride can improve bowel movements in children and teenagers with functional constipation. Another aim is to check for side effects from 2 different doses of prucalopride. The main aim of the 2nd part of the study is to continue to check for side effects from 2 different doses of prucalopride.
In the 1st part, at the first visit, the study doctor will check who can take part. Participants who take part will be picked for 1 of 3 treatments by chance.
- A low dose of prucalopride once a day.
- A higher dose of prucalopride once a day.
- A placebo once a day. In this study, a placebo will look like prucalopride but will not have any medicine in it. Participants will be treated with prucalopride or a placebo for 12 weeks.
Participants who took prucalopride will continue to the 2nd part of the study. They will have the same treatment as they did in the 1st part of the study. They will continue with their treatment for another 36 weeks. Participants who took placebo in the 1st part of the study will receive prucalopride in the 2nd part of the study. They will be picked for a low dose or a high dose of prucalopride by chance.
Participants will visit the clinic a few times during treatment. The clinic staff will also telephone the participants, or their parents or caregivers throughout treatment for a check-up 4 weeks after last treatment, the clinic staff will telephone the participants, or their parents or caregivers for a final check-up.
Detailed description
This study consists of a 12-week double-blind, placebo-controlled part (Part A) followed by a 36-week double-blind safety extension part (Part B). Participants aged 3 to 17 years are planned for randomization in a 1:1:1 ratio to the Low Dose Group, High Dose Group, or matching placebo (placebo-controlled part [Part A]). After completion of Part A, participants in the placebo group will be re-randomized in a 1:1 ratio to the Low Dose Group or the High Dose Group (safety extension part [Part B]). Randomization at study entry will be stratified by toilet-trained status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: Placebo | Placebo comparator | Other: PlaceboParticipants weighing <50 kilograms (kg) will draw equal volumes from two bottles of placebo oral solution to account for the daily dose assigned or participants weighing ≥ 50 kg will receive two placebo oral tablets, once daily (QD), during 12 weeks in Part A. Prucalopride matching placebo (oral solution or tablet) will be dosed depending on the participant's body weight (BW) at the randomization visit. |
| Part A: Low Dose Prucalopride | Experimental | Drug: PrucaloprideParticipants weighing <50 kg will receive 0.04 milligrams per kilogram (mg/kg) of prucalopride oral solution (will draw 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 will receive 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) will be dosed depending on the participant's BW at the randomization visit. |
| Part A: High Dose Prucalopride | Experimental | Drug: PrucaloprideParticipants weighing <50 kg will receive 0.08 mg/kg of prucalopride oral solution (will draw the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg will receive two 2 mg of prucalopride oral tablets, QD, during 12 weeks of treatment period in Part A. Prucalopride (oral solution or tablet) will be dosed depending on the participant's BW at the randomization visit. |
| Part B: Low Dose Prucalopride | Experimental | Drug: PrucaloprideParticipants weighing <50 kg will receive 0.04 mg/kg of prucalopride oral solution (will draw 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 will receive 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) will be dosed depending on the participant's BW at the randomization visit. |
| Part B: High Dose Prucalopride | Experimental | Drug: PrucaloprideParticipants weighing <50 kg will receive 0.08 mg/kg of prucalopride oral solution (will draw the required volume from two bottles of 0.4 mg/mL to account for the daily dose assigned), QD or participants weighing ≥50 kg will receive two 2 mg of prucalopride oral tablets, QD, for 36 weeks during the 40-week Part B Period. Prucalopride (oral solution or tablet) will be dosed depending on the participant's BW at the randomization visit. |
Who may qualify
- Ages
- 6 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (27 listed)
- Participants and/or their parent(s)/caregiver(s)/legally authorized representative(s) have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Ability to voluntarily provide written, signed, and dated (personally or via parent[s]/caregiver[s]/legally authorized representative[s]) informed consent/assent as applicable to participate in the study.
- Note: Participants and/or parent(s)/caregiver(s)/legally authorized representative(s) (where appropriate depending on age and local regulation) can also provide consent/assent to the sparse Pharmacokinetic (PK) sampling in this study.
- Toilet-trained participants 3 years to 17 years of age, inclusive, or non-toilet-trained participants 6 months to 17 years of age, inclusive.
- Participant weighs greater than or equal to (>=) 5.5 kilograms (kg) (12 pounds [lbs]).
Key exclusion criteria (37 listed)
- Current or recurrent disease that could affect the action, absorption, or disposition of the investigational product (IP), or clinical or laboratory assessments.
- Any clinically significant abnormal findings on the electrocardiogram (ECG) that indicates a dysrhythmia or conduction abnormalities (such as abnormal heart rate, PR, QRS, or QT).
- Major cardiovascular disease such as: cardiomyopathy, cardiac insufficiency, uncorrected congenital heart disease, symptomatic valve disorders, or septal defects.
- Current or relevant history of physical or psychiatric illness (e.g. severe autism, depression, etc.), any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the IP or procedures.
- Non-retentive fecal incontinence.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrucaloprideAlso: TAK-555, Prucalopride succinatePrucalopride oral solution or oral tablets. | Drug | Part A: High Dose Prucalopride, Part A: Low Dose Prucalopride, Part B: High Dose Prucalopride, Part B: Low Dose Prucalopride |
| PlaceboPrucalopride-matching placebo oral solution or oral tablets. | Other | Part A: Placebo |
Primary outcome
Part A: Change From Baseline in Average Number of Weekly Number of Spontaneous Bowel Movements (SBMs) at Week 12
Time frame: Baseline, Week 12
Spontaneous bowel movement was defined as a bowel movement that was not preceded within a period of 24 hours by the intake of rescue medication. The average change from baseline in number of SBMs per week derived from the (e-diary) data, in toilet-trained participants who were at least 3 years of age collected during the placebo-controlled part (Part A) was assessed.
Parts A and B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study drug up to Week 52
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with an investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the IP or medicinal product. A serious adverse event (SAE) was any untoward medical occurrence (whether considered to be related to 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.
Parts A and B: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters
Time frame: 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.
Parts A and B: Number of Participants With Clinically Significant Vital Sign Abnormalities
Time frame: 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.
Parts A and B: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Time frame: 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.
4 secondary outcomes
Part A: Change From Baseline in Participants' Weekly Stool Consistency Based on Bristol Stool Form Scale (BSFS) Score at Week 12 Categorized by Age
Time frame: Baseline, Week 12
Part A: Change From Baseline in Weekly Straining Score Based on a 3-point Likert Scale at Week 12
Time frame: Baseline, Week 12
Part A: Percentage of Responders Based on Assessment of SBMs
Time frame: Baseline through Week 12
Part A: Percentage of Participants With Fecal Incontinence at Week 12
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37215389Cuffari C, Spalding W, Achenbach H, Thakur M, Gabriel A. Design of a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of prucalopride in pediatric patients with functional constipation. Contemp Clin Trials Commun. 2023 Apr 30;33:101144. doi: 10.1016/j.conctc.2023.101144. eCollection 2023 Jun.
- To obtain more information on the study, click here/on this linkLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
41 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Prucalopride in people with Constipation, run by Takeda at 41 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Change From Baseline in Average Number of Weekly Number of Spontaneous Bowel Movements (SBMs) at Week 12 (time frame: Baseline, Week 12). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04759833, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024.