Effect of PEG, Bisacodyl and Prucalopride on Colonic Motility in Healthy Subjects

Study Overview
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Brief Summary
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This study aim was to evaluate the effect of pharmacological treatments normally used to treat functional constipation and in particular PEG, bisacodyl and prucalopride on colonic motility as assessed by high-resolution manometry.

Detailed Description
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Rationale: Several treatments with different modes of action are currently available for chronic constipation. This study will investigate the effect of these different modes of actions of PEG 3350 + electrolytes, bysacodyl and prucalopride and on colonic motility parameters (e.g. HAPC). Objectives:Primary: to compare and determine the effects of PEG, bisacodyl and prucalopride on the number of colonic high amplitude propagated contractions (HAPCs) during a 12-hour intraluminal manometry in healthy subjects. Secondary: to evaluate the association between motility parameters and number and consistency of bowel movements in healthy subjects. Investigational product, dose, and mode of administration: Regimen A: 13.8g polyethylene glycol 3350 with sodium bicarbonate, sodium chloride, and potassium chloride, mixed with 125mL of water administered twice orally as a solution. Regimen B: 10 mg bisacodyl once daily oral administration with 125mL of water. Regimen C: 2mg prucalopride, film-coated tablets (prucalopride succinate eq. 2mg), once daily oral administration with 125mL of water. Methodology: This is an open-label, randomized, reader-blinded, 3-period cross-over study investigating the effects of PEG 3350 + electrolytes, bisacodyl and prucalopride on colon motility with intraluminal manometry. On day 1 of each Treatment Period, a manometry catheter will be placed in the colon under conscious sedation and the colonic pressure will be continuously measured through 12 hours after administration of each of the investigational products (Regimen A, B or C). Inclusion criteria: healthy male and non-pregnant, non-breastfeeding female participants, aged 18-65 years old at the time of consent. Exclusion criteria: use of medications within 48 h of dose initiation; structural or metabolic diseases that affect the gastrointestinal system and functional gastrointestinal disorders; previous abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, or hernia repair; known illnesses such as diabetes, cardiovascular or lung disease; use of agents that influence bowel habit, i.e. anticholinergics (not including antihistamines with anticholinergic properties), spasmolytics and prokinetics in the 7 days before the study.

Official Title
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An Open-label, Randomised, Crossover, Reader Blinded, Study to Compare the Effect of Polyethylene Glycol 3350, Bisacodyl and Prucalopride on Colonic Motility Assessed With Intraluminal Colonic Manometry in Healthy Subjects

Conditions
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Chronic Constipation

Intervention / Treatment
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* Drug: polyethylene glycol
* Drug: Bisacodyl
* Drug: Prucalopride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy male and non-pregnant, non-breastfeeding female participants, aged 18-65 years old at the time of consent Exclusion Criteria: use of medications within 48 h of dose initiation; structural or metabolic diseases that affect the gastrointestinal system and functional gastrointestinal disorders; previous abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, or hernia repair; known illnesses such as diabetes, cardiovascular or lung disease; use of agents that influence bowel habit, i.e. anticholinergics (not including antihistamines with anticholinergic properties), spasmolytics and prokinetics in the 7 days before the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: open-label, randomized, reader-blinded, 3-period cross-over study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: polyethylene glycol, osmotic laxitive<br>13.8g polyethylene glycol 3350 with sodium bicarbonate, sodium chloride, and potassium chloride, mixed with 125mL of water administered twice orally as a solution | Drug: polyethylene glycol<br>* osmotic laxative<br>* Other names: PEG;|
| Active Comparator: bisacodyl, stimulant laxative<br>10 mg bisacodyl once daily oral administration with 125mL of water | Drug: Bisacodyl<br>* stimulant laxative<br>* Other names: Dulcolax;|
| Active Comparator: prucalopride, prokinetic<br>2mg prucalopride, film-coated tablets (prucalopride succinate eq. 2mg), once daily oral administration with 125mL of water | Drug: Prucalopride<br>* prokinetic<br>* Other names: Resolor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| colonic motor patterns during PEG, bisacodyl and prucalopride in healthy subjects. | number of colonic high amplitude propagated contractions (HAPCs) | during a 12-hour intraluminal manometry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| association between motility parameters and number and consistency of bowel movements in healthy subjects | number of colonic motor patterns and number of bowel movements and stool consistency assessed by Bristol Stool Chart | during a 12-hour intraluminal manometry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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laxatives, constipation