Prucalopride for Constipation

No longer recruiting at 48 trial locations

Overseen By Contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Must not be taking: Opioids

Disqualifiers: Cardiovascular disease, Renal impairment, Psychiatric illness, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether prucalopride can help children and teens with functional constipation, a condition where bowel movements are difficult without another health issue or medication causing it. The study tests two doses of prucalopride to assess improvements in bowel movements and checks for side effects. Suitable participants are children aged 3 to 17 who have fewer than two bowel movements a week and experience issues like painful or hard bowel movements or stool retention. Participants will take either prucalopride or a placebo for 12 weeks, with those on prucalopride continuing for another 36 weeks to monitor long-term effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants who are currently using any medication that could affect the condition being studied or the study drug, including over-the-counter and herbal remedies, within the past 5 days.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that prucalopride is generally well-tolerated. A large review of 17 studies, involving about 3,300 patients, found prucalopride safe compared to a placebo, a non-active pill. Side effects in those taking prucalopride were similar to those taking the placebo. Another study tested prucalopride in older adults over four weeks and found it safe. Importantly, no major differences in heart-related issues appeared between those taking prucalopride and those on a placebo.

These results align with evidence indicating that prucalopride does not increase heart problems compared to other treatments. However, reactions can vary, and side effects may differ among individuals. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for constipation?

Prucalopride is unique because it specifically targets and activates serotonin receptors in the gut, which helps stimulate bowel movements. Unlike traditional treatments for constipation, like fiber supplements or laxatives, prucalopride works directly on the muscles of the intestines to enhance motility. Researchers are excited about prucalopride because it offers a more direct approach to treating chronic constipation, potentially providing relief for those who haven't had success with existing options.

What evidence suggests that prucalopride might be an effective treatment for functional constipation?

Research has shown that prucalopride can help people with long-term constipation have more frequent bowel movements. Over 12 weeks, studies found that prucalopride significantly improves bowel function and eases constipation symptoms. In this trial, participants will receive either a low or high dose of prucalopride, or a placebo, to evaluate its effectiveness. One large study found that most patients with chronic constipation felt better after using prucalopride. It specifically helped reduce symptoms like belly pain after a few months. Prucalopride encourages bowel movements, making it easier to pass stools. Overall, these findings suggest that prucalopride could be a promising option for treating constipation. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for children and teenagers aged 6 months to 17 years with functional constipation, which means they have difficulty passing stools not caused by other health issues or medications. They must weigh at least 5.5 kg (12 lbs), be toilet-trained if over 3 years old, and experience less than three bowel movements per week among other specific criteria related to stool characteristics.

Inclusion Criteria

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.

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.

Exclusion Criteria

Celiac disease, cow milk allergy

Known history of alcohol or other substance abuse within the last year.

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).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive either a low dose, high dose of prucalopride, or placebo for 12 weeks to evaluate efficacy and safety

12 weeks

Multiple visits (in-person and telephone)

Treatment Part B

Participants continue with prucalopride treatment for an additional 36 weeks to document long-term safety

36 weeks

Multiple visits (in-person and telephone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 telephone visit

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Prucalopride

Trial Overview

The study tests prucalopride's effectiveness in improving bowel movements in young patients with functional constipation. It has two parts: the first part randomly assigns participants to a low dose of prucalopride, a higher dose, or a placebo for 12 weeks; the second part continues treatment for another 36 weeks, with placebo group members switching to prucalopride.

How Is the Trial Designed?

Group I: Part B: Low Dose Prucalopride Experimental Treatment 1 Intervention

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.

Group II: Part B: High Dose Prucalopride Experimental Treatment 1 Intervention

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.

Group III: Part A: Low Dose Prucalopride Experimental Treatment 1 Intervention

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.

Group IV: Part A: High Dose Prucalopride Experimental Treatment 1 Intervention

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.

Group V: Part A: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

A study analyzing 31,542 adverse event reports from the FDA found that semaglutide, a GLP-1 analogue, has a higher potential for misuse and abuse compared to other GLP-1 receptor agonists, with significant reporting odds ratios for issues like drug abuse and withdrawal syndrome.

The findings suggest that semaglutide may be misused as a weight-loss treatment in non-obese individuals, highlighting the need for further research to fully understand its safety profile and the implications of its use outside of approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset. Chiappini, S., Vickers-Smith, R., Harris, D., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4930296/

Use of Prucalopride for Chronic Constipation - PubMed Central

Prucalopride successfully increased the frequency of spontaneous bowel movements per week in all variable doses of 1 mg (standardized mean difference [SMD], ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa0800670

A Placebo-Controlled Trial of Prucalopride for Severe ...

Over 12 weeks, prucalopride significantly improved bowel function and reduced the severity of symptoms in patients with severe chronic constipation.

3.

journals.lww.com

journals.lww.com/ctg/fulltext/2024/05000/clinical_outcomes_before_and_after_prucalopride.6.aspx

Clinical Outcomes Before and After Prucalopride Treatment:...

The proportions of patients overall with constipation-related symptoms decreased 6 months after prucalopride initiation (abdominal pain [50.4% vs 33.3%, P < ...

4.

jnmjournal.org

jnmjournal.org/journal/view.html?doi=10.5056/jnm16004

Use of Prucalopride for Chronic Constipation: A Systematic ...

Sixteen randomized, controlled trials on 3943 patients reported the effectiveness of prucalopride in patients with chronic constipation. Prucalopride ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38357940/

Clinical Outcomes Before and After Prucalopride Treatment

The proportions of patients overall with constipation-related symptoms decreased 6 months after prucalopride initiation (abdominal pain [50.4% ...

6.

ema.europa.eu

ema.europa.eu/en/documents/product-information/resolor-epar-product-information_en.pdf

Resolor, INN-prucalopride - EMA

Summary of the safety profile. In an integrated analysis of 17 double-blind placebo-controlled studies, Resolor was given orally to approximately 3,300 patients ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/19751247/

Safety assessment of prucalopride in elderly patients with ...

Prucalopride up to 2 mg once daily for 4 weeks was safe and well-tolerated by constipated elderly patients, with no differences vs placebo in ECG or a range of ...

8.

fda.gov

fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM623496.pdf

Prucalopride for the Treatment of Chronic Idiopathic ...

Each data source supports the cardiovascular safety of prucalopride, and the totality of the data could not establish an increase in ...

9.

mayoclinic.org

mayoclinic.org/drugs-supplements/prucalopride-oral-route/description/drg-20452343

Prucalopride (oral route) - Side effects & dosage

Prucalopride is used to treat chronic idiopathic (unknown cause) constipation (CIC). ... Safety and efficacy have not been established.

10.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3263983/

Prucalopride: safety, efficacy and potential applications

(2008) Safety and tolerability of prucalopride (Resolor®) in patients with chronic constipation: pooled data from three pivotal phase III studies [abstract].