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

Study Overview
=================
Brief Summary
-----------------
To evaluate the different effects of prucalopride and PEG 3350 + electrolytes on colon motor activity in subjects that are chronically constipated.

Official Title
-----------------
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

Conditions
-----------------
Chronic Constipation

Intervention / Treatment
-----------------
* Drug: prucalopride
* Drug: PEG 3350


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prucalopride<br> | Drug: prucalopride<br>* One 2 mg tablet orally administered on Day 1<br>* Other names: Resolor (Marketed name in Europe);|
| Active Comparator: PEG 3350<br> | Drug: PEG 3350<br>* 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).<br>* 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 |