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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Constipation
• Intervention / Treatment: Drug: polyethylene glycol; Drug: Bisacodyl; Drug: Prucalopride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • TARGID

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: polyethylene glycol, osmotic laxitive; 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; osmotic laxative; Other Names: PEG; macrogol
Active Comparator: bisacodyl, stimulant laxative; 10 mg bisacodyl once daily oral administration with 125mL of water	Drug: Bisacodyl; stimulant laxative; Other Names: Dulcolax
Active Comparator: prucalopride, prokinetic; 2mg prucalopride, film-coated tablets (prucalopride succinate eq. 2mg), once daily oral administration with 125mL of water	Drug: Prucalopride; prokinetic; Other Names: Resolor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Gasthuisberg
• Investigators: Principal Investigator: Jan Tack, MD. PhD, KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: laxatives; constipation
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Cathartics; Laxatives; Serotonin 5-HT4 Receptor Agonists; Bisacodyl; Prucalopride
• Other Study ID Numbers: S54750

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No