Evaluation of Long-term Prucalopride Treatment With Chronic Constipation in Subjects Aged ≥ 18 Years

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the long-term (24 weeks) efficacy of prucalopride versus placebo in subjects aged 18 years and older with chronic constipation.

Detailed Description
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In this phase IV trial a total of 340 subjects (170 subjects per treatment group), with chronic constipation, are planned to be randomly assigned to double-blind treatment. The trial duration for a subject can be 26 to 28 weeks in total, including a 2- to 4-week run-in phase followed by a 24-week double-blind treatment phase. The patient will complete an e-diary. Adult subjects (≥18 to <65 years of age) will take 2 mg prucalopride or matching placebo throughout the entire 24-week treatment period. Elderly subjects (≥65 years of age) will start at a dose of 1 mg prucalopride or matching placebo. In case of insufficient response the daily dose has to be increased to 2 mg (i.e. changed to 2 mg prucalopride or matching placebo).

Official Title
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A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Quality of Life, Safety and Tolerability of Long-term Treatment (24 Weeks) With Prucalopride in Subjects Aged ≥18 Years With Chronic Constipation

Conditions
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Constipation

Intervention / Treatment
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* Drug: placebo
* Drug: prucalopride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a male or non-pregnant, non-breastfeeding female out-patient ≥18 years of age (no upper age limit). Subject has a history of constipation. The subject reports an average of ≤2 SBM/week that result in a feeling of complete evacuation (SCBM). Subject agrees to stop his/her current laxative treatment and is willing to use rescue medication according to the rescue rule [bisacodyl/enemas]. Exclusion Criteria: Subjects in whom constipation is thought to be drug-induced Subjects using any disallowed medication. Subjects who previously used prucalopride. Subjects suffering from secondary causes of chronic constipation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo 2 mg tablet once daily before breakfast | Drug: placebo<br>* Placebo matching tablet 2 mg once daily before breakfast for 24 weeks<br>|
| Active Comparator: prucalopride<br>Prucalopride 2 mg once daily before breakfast | Drug: prucalopride<br>* Prucalopride 2 mg daily before breakfast 1 mg for subjects >65 years; in case of insufficient response 2 mg at week 2 or week 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects With an Average of ≥3 Spontaneous Complete Bowel Movements (SCBM) Per Week Over the 24 Week Treatment Period | Spontaneous Bowel Movements defined as a bowel movement that is not preceded within a period of 24 hours by the intake of a laxative agent or by the use of an enema. | Over 24 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With an Increase of ≥1 Spontaneous Complete Bowel Movement (SCBM) Per Week Up to 24 Weeks |  | Over 24 week treatment period | 
| Average Number of Spontaneous Complete Bowel Movements (SCBM) Per Week Up to 24 Weeks |  | Over 24 week treatment period | 
| Change From Baseline in Spontaneous Complete Bowel Movements Per Week at Up to 24 Weeks |  | Baseline and Over 24 week treatment period | 
| Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by Week |  | Over 24 week treatment period | 
| Percent of Subjects With an Average Weekly Frequency of at Least 3 SCBM by 4-Week Treatment Period |  | Over 24 week treatment period | 
| Change From Baseline in Average Consistency Per SCBM at Up to 24 Weeks | Consistency measured using the 7-point Bristol scale where 1-2 indicate constipation (=hard/very hard), 3-4 are ideal stools (=normal), and 5-7 tending toward diarrhea. | Baseline and Over 24 week treatment period | 
| Change From Baseline in Percent SCBM With a Consistency of Normal and Hard/Very Hard at Up to 24 Weeks |  | Baseline and Over 24 week treatment period | 
| Change From Baseline in Straining Per SCBM at Up to 24 Weeks | Straining was evaluated on a 5-point scale (0=none, 1=mild, 2=moderate, 3=severe, or 4=very severe) | Baseline and Over 24 week treatment period | 
| Change From Baseline in Percent SCBM With No Straining and Severe/Very Severe Straining at Up to 24 Weeks |  | Baseline and Over 24 week treatment period | 
| Change From Baseline in Percent SBM With Sensation of Complete Evacuation at Up to 24 Weeks |  | Baseline and Over 24 week treatment period | 
| Time to First SCBM After Investigational Product Intake on Day 1 and Day 28 |  | Day 1 and 28 | 
| Change From Baseline in the Number of Bisacodyl Tablets Taken Per Week at Up to 24 Weeks |  | Baseline and Over 24 week treatment period | 
| Change From Baseline in the Number of Days With Rescue Medication Taken Per Week at Up to 24 Weeks | Rescue medications include laxatives and enemas. | Baseline and Over 24 week treatment period | 
| Change From Baseline in the Patient Assessment of Constipation - Symptom (PAC-SYM) Questionnaire Score at Up to the Final On Treatment Assessment Value | The PAC-SYM is a validated 12-item questionnaire for the evaluation of severity of symptoms of constipation in subjects with constipation. Items are rated on a 5-point Likert scale: 0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe. Total score ranges from 0 to 48. Lower scores indicate improvement in symptoms. A 1-point improvement in PAC-SYM total score was considered clinically meaningful. | Baseline and Over 24 week treatment period | 
| Change From Baseline in the Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score at Up to the Final On Treatment Assessment Value | The PAC-QOL is a validated 28-item questionnaire for the evaluation of quality of life in subjects with constipation. Items are rated on a 5-point Likert scale: 0=not at all/none of the time, 1=a little bit/a little bit of the time, 2=moderately/some of the time, 3=quite a bit/most of the time, 4=extremely/all of the time. Total score ranges from 0-112. Lower scores indicate improvement in symptoms. A 1-point improvement in PAC-QOL total score was considered clinically meaningful. | Baseline and Over 24 week treatment period | 
| Change From Baseline in the Short Form-36 Health Survey (SF-36) Score at Up to the Final On Treatment Assessment Value | The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Total score ranges from 0 (lowest level of health) - 100 (highest level of health) on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability). Higher scores are associated with better quality of life. | Baseline and Over 24 week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long term, Constipation, Digestive signs and symptoms