A Study of Prucalopride For Functional Constipation in Children and Teenagers

NCT04759833 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: TAK-555-30102022-003221-22
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 41

Brief 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. 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.

Conditions

Constipation

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  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

  Baseline, Week 12

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

  Baseline, Week 12

• Part A: Percentage of Responders Based on Assessment of SBMs

  Baseline through Week 12

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

  Week 12

Other Outcomes (1)

• Part A: Pharmacokinetic (PK) Plasma Concentrations of Prucalopride

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

Study Arms (5)

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.

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.

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.

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.

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.

Drug: Prucalopride

Interventions

Prucalopride DRUG

Prucalopride oral solution or oral tablets.

Also known as: TAK-555, Prucalopride succinate

Part A: High Dose Prucalopride; Part A: Low Dose Prucalopride; Part B: High Dose Prucalopride; Part B: Low Dose Prucalopride

Placebo OTHER

Prucalopride-matching placebo oral solution or oral tablets.

Part A: Placebo

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (41)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Novak Clinical Research

Tucson, Arizona, 85741, United States

Location

Eclipse Clinical Research

Tucson, Arizona, 85745, United States

Location

Advanced Research Center, Inc.

Anaheim, California, 92805, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California, Davis Department of Pediatrics

Sacramento, California, 95817, United States

Location

University of California

San Francisco, California, 94158, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Direct Helpers Research Center

Hialeah, Florida, 33012, United States

Location

Pediatric & Adult Research Center

Kissimmee, Florida, 34741, United States

Location

Auzmer Research

Lakeland, Florida, 33813, United States

Location

University of Miami - Miller School of Medicine

Miami, Florida, 33136, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Florida Research Center, Inc.

Miami, Florida, 33174, United States

Location

Orlando Health - APH Center for Digestive Health and Nutrition

Orlando, Florida, 32806, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

GI Pediatric Subspecialty Clinic

Peoria, Illinois, 61603, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Willis-Knighton Center for Pediatric Gastroenterology & Advanced Endoscopy

Shreveport, Louisiana, 71118, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Baystate Health

Springfield, Massachusetts, 01199, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

CUMC Pediatrics-GI

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Cyn3rgy Research & Development

Gresham, Oregon, 97030, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

GI For Kids

Knoxville, Tennessee, 37922, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38105, United States

Location

Tekton Research, Inc.

Beaumont, Texas, 77706, United States

Location

Cedar Health Research

Dallas, Texas, 75251, United States

Location

Allure Health LLC

Friendswood, Texas, 77546, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Pediatric Associates

Houston, Texas, 77087, United States

Location

Pediatric Center

Richmond, Texas, 77469, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Pediatric Specialist of Virginia

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• 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.

  PMID: 37215389 DERIVED

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Constipation

Interventions

prucalopride

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 18, 2021
• Study Start: July 13, 2021
• Primary Completion: November 13, 2023
• Study Completion: November 13, 2023
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (41)