Prucalopride for Constipation

Recruiting at 45 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

175 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests prucalopride, a medicine that helps improve bowel movements, in children and teenagers aged 3 to 17 with functional constipation. The study will check if prucalopride works and if it has any side effects. Participants will be given either a low dose or a high dose for several months, with an option to continue for a longer period. Prucalopride has been shown to improve bowel function in adults with chronic constipation.

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.

What data supports the effectiveness of the drug Prucalopride for treating constipation?

Research shows that Prucalopride is effective in improving bowel habits and relieving symptoms of chronic constipation, especially in patients who did not find relief with other treatments. Studies have demonstrated significant improvements in patient satisfaction and quality of life compared to a placebo. ^{1 2 3 4 5}

Is prucalopride safe for humans?

Prucalopride has been studied for safety, particularly regarding its effects on the heart. A large study found that it did not increase the risk of major heart problems like heart attacks or strokes compared to another treatment for constipation. ^{6 7 8 9 10}

How is the drug Prucalopride different from other treatments for constipation?

Prucalopride is unique because it is a 5-HT4 receptor agonist (a type of drug that stimulates specific receptors in the gut to enhance movement) and is specifically used for people who do not get relief from regular laxatives. It is particularly effective for chronic constipation and related conditions, offering an alternative when other treatments fail. ^{1 2 11 12 13}

Research Team

Medical Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety/Efficacy of Prucalopride in Korean Patients with Chronic Constipation: Post-marketing Surveillance. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies. [2012]

3. England pubmed.ncbi.nlm.nih.gov

Association between health-related quality of life and symptoms in patients with chronic constipation: an integrated analysis of three phase 3 trials of prucalopride. [2016]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Prucalopride. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Identification and Validation of Major Cardiovascular Events in the United Kingdom Data Sources Included in a Multi-database Post-authorization Safety Study of Prucalopride. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Factors predictive of treatment-emergent adverse events of prucalopride: an integrated analysis of four randomized, double-blind, placebo-controlled trials. [2022]

8. Switzerland 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. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database. [2023]

10. England 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. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of prucalopride on the pharmacokinetics of oral contraceptives in healthy women. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Prucalopride for the treatment of constipation: a view from 2015 and beyond. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Prucalopride: evaluation of the pharmacokinetics, pharmacodynamics, efficacy and safety in the treatment of chronic constipation. [2018]