Study to Investigate Prucalopride vs. Polyethylene Glycol 3350 on Colon Activity

An Open-label, Randomized, Crossover, Reader-blinded Study to Investigate the Effect of Prucalopride and Polyethylene Glycol 3350 on Colon Motility With Intramural Manometry in Subjects With Chronic Constipation

To evaluate the different effects of prucalopride and PEG 3350 + electrolytes on colon motor activity in subjects that are chronically constipated.

Study Overview

• Status: Completed
• Conditions: Chronic Constipation
• Intervention / Treatment: Drug: prucalopride; Drug: PEG 3350

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UNIVERSITY OF LEUVEN, UNVERSITY HOSPITAL, Gasthuisberg
• United Kingdom
  • London
    • Whitechapel, London, United Kingdom, E1 1BB
      • Barts Health NHS Trust
• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Foundation for Digestive Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic constipation
• Male or female ages 18-75 years
• Non-pregnant, non-lactating female

Exclusion Criteria:

• Drug-induced constipation
• Subjects suffering from secondary causes of chronic constipation, such as:
• Endocrine disorders, e.g. hypopituitarism, hypothyroidism, hypercalcemia, pseudohypoparathyroidism, pheochromocytoma or glucagon-producing tumors, unless these are controlled by appropriate medical therapy.
• Metabolic disorders, e.g. porphyria, uremia, hypokalemia or amyloid neuropathy, unless these are controlled by appropriate medical therapy
• Neurological disorders, e.g. Parkinson's disease, cerebral tumors, cerebrovascular accidents, multiple sclerosis, meningocele, aganglionosis, hypoganglionosis, hyperganglionosis, autonomic neuropathy or neuropathy due to chemotherapy, spinal cord injury, Chaga's disease, or major depression
• Surgery.
• Subjects with insulin-dependent diabetes mellitus
• Rectal evacuation disorder/outlet obstruction
• Subjects with intestinal perforation or obstruction
• Severe renal impairment
• Subjects with a history of alcohol or drug abuse
• Subjects with lactose intolerance
• Subjects with clinically significant cardiac, vascular, liver, pulmonary, endocrine, neurological or psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Prucalopride	Drug: prucalopride; One 2 mg tablet orally administered on Day 1; Other Names: Resolor (Marketed name in Europe)
ACTIVE_COMPARATOR: PEG 3350	Drug: PEG 3350; 13.8g polyethylene glycol (PEG) 3350 with sodium bicarbonate, sodium chloride, and potassium chloride as a solution in water. Administered twice orally on Day 1(once in the morning and once prior to lunch).; Other Names: Movicol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of High-Amplitude Propagating Contractions (HAPC)	Manometry recordings were read by an experienced gastroenterologist who was blinded to the treatment each subject received. The tracings were analyzed using computer-based validated software. HAPC and manometry data were available for every sensor as well as average values for each HAPC and manometry time point. The primary outcome analysis of HAPC data used the following threshold: Mean amplitude ≥100mmHg and extension ≥20cm (9 sensors).	over 12 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration Curve (AUC) of All HAPCs	The AUC of all HAPCs during the first 12 hours after treatment was calculated as the sum of the AUC at all sensors of each HAPC at the ≥100mmHg and ≥20cm threshold.	over 12 hours post-dose
The Mean Amplitude of HAPC	The mean amplitude of all HAPCs was calculated as the sum of the mean amplitude for each HAPC divided by the number of HAPCs.	over 12 hours post-dose
Time to First HAPC	The median (95% CI) time to first HAPC after administration of investigational product with amplitude ≥100mmHg and extension ≥20cm.	over 12 hours post-dose
Propagation Velocity of HAPC	Propagation velocity was calculated as the extension divided by the duration for each HAPC. Mean propagation velocity is the sum of the propagation velocities divided by the number of HAPCs.	over 12 hours post-dose
Duration of HAPC	The mean duration of all HAPCs was calculated as the sum of the duration of each HAPC divided by the number of HAPCs.	over 12 hours post-dose
Motility Index	Motility index (mmHg) was summarized for the following 3 time points: pre-dose, 0-5 hours post-dose, and 5-12 hours post-dose. The motility index is defined as the natural logarithm of all peak amplitudes of every contraction +1.	over 12 hours post-dose

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Miner PB Jr, Camilleri M, Burton D, Achenbach H, Wan H, Dragone J, Mellgard B. Prucalopride induces high-amplitude propagating contractions in the colon of patients with chronic constipation: a randomized study. Neurogastroenterol Motil. 2016 Sep;28(9):1341-8. doi: 10.1111/nmo.12832. Epub 2016 Jun 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 27, 2013
• Primary Completion (ACTUAL): November 27, 2013
• Study Completion (ACTUAL): November 27, 2013

Study Registration Dates

• First Submitted: October 12, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (ESTIMATE): October 16, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• 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; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride; Polyethylene glycol 3350
• Other Study ID Numbers: SPD555-403; 2012-002495-13 (EUDRACT_NUMBER)