E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063582 |
E.1.2 | Term | Constipation chronic |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of prucalopride versus placebo over 12 weeks of treatment in male subjects with chronic constipation |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety, tolerability, effect on quality of life and effect on symptoms of prucalopride versus placebo over 12 weeks of treatment in male subjects with chronic constipation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria to be assessed at screening:
1. Subject is a male out-patient ≥18 years of age (no upper age limit).
2. Subject has a history of constipation, i.e. reports an average of ≤2 spontaneous bowel movements (SBM)/week that result in a feeling of complete evacuation (SCBM) and one or more of the following for at least 6 months before the selection visit:
a) Very hard (little balls) and/or hard stools for at least a quarter of the stools;
b) Sensation of incomplete evacuation following for at least a quarter of stools;
c) Straining at defecation for at least a quarter of the time.
The above criteria are only applicable for SBMs, i.e. BMs not preceded within a period of 24 hours by the intake of a laxative agent or by the use of an enema. Subjects who never have SBMs are considered to be constipated and are eligible for the trial.
3. Subject agrees to stop his current laxative treatment and is willing to use rescue.
Main inclusion criteria to be assessed at baseline (randomisation):
1. During the run-in period, the subject reports an average of ≤2 SBM/week that result in a feeling of complete evacuation (SCBM).* This includes subjects who never have SBMs.
2. Subject stopped his/her laxative treatment and did not use rescue mediation on more than 75% of days during the run-in period.* medication according to the rescue rule [Dulcolax® (bisacodyl)/ enemas].
3. Subject did not use disallowed medication during the run-in period.
* Excluding the first 7 days for subjects using medication influencing bowel habit or excluding the days between screening and the 7 days following the colonoscopy/sigmoidoscopy for those who had a colonoscopy/sigmoidoscopy after screening. |
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E.4 | Principal exclusion criteria |
1. Subjects in whom constipation is thought to be drug-induced.
2. Subjects using any disallowed medication.
3. Subjects suffering from secondary causes of chronic constipation.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary parameter is the proportion (%) of subjects with an average of ≥3 SCBMs/week (i.e. a responder) over the 12-week double-blind treatment period.
If e-diary data are available for less than 28 days, the subject will be considered a non-responder for the primary analysis.
The Cochran-Mantel-Haenszel test controlling for the randomisation stratification factors (country and CBM) will be used to compare treatment groups.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The key evaluation period will be the 24-week double-blind treatment phase. This endpoint will also be evaluated in periods of 4 weeks and per week of treatment |
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E.5.2 | Secondary end point(s) |
A:
• Proportion (%) of subjects with an average increase of ≥1 (SC)BM/week compared to the run-in period, over the entire treatment period
• The average number of (SC)BM/week and change from baseline
• Number of (SC)BMs per week: descriptive statistics and distribution in categories as 0, (0;1), [1;2), [2;3), [3;->)
• Consistency per (SC)BM: descriptive statistics of 7-point score and % (SC)BM with normal consistency (Type 3 or 4 on the Bristol stool scale)
• Straining per (SC)BM: descriptive statistics of 5-point score and % (SC)BM with no straining and with severe/very severe straining
• The proportion (%) of subjects with ≥3 (SC)BM/week and with ≥50% of (SC)BM with Type 3 or 4 on the Bristol stool scale and mild or moderate straining
• Sensation of complete evacuation per (S)BM: % (S)BM with sensation of complete evacuation
• Average time to first (SC)BM after the first intake of the trial medication (Day 1) and after the intake on Day 29 (Week 4)
• Average number of bisacodyl (Dulcolax®) tablets taken per week and the average number of days with bisacodyl (Dulcolax®) use per week
B:
• Subject’s global assessment on severity of constipation (5-point scales; 0=none, 4=very severe)
• Subject’s global assessment on efficacy of treatment (5-point scales; 0=none, 4=extremely effective)
• Subject’s lower GI symptom assessment by the PAC-SYM total score, subscale scores (stool symptoms, abdominal symptoms and rectal symptoms) and individual item scores (5 point scales; 0=none, 4=very severe) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
A number of secondary parameters will be derived from the e-diary and evaluated over similar periods. The primary parameter and the below secondary parameters in Category A will be evaluated over 12-week and 4 week periods, and per individual week of treatment.
Secondary parameters in category B will be summarised per scheduled visits and endpoint (last observation carried forward, LOCF), for both observed values and changes from baseline. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |