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 | PT |
E.1.2 | Classification code | 10010774 |
E.1.2 | Term | Constipation |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 long-term (24 weeks) efficacy of prucalopride versus placebo in subjects aged 18 years and older with chronic constipation. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term safety, tolerability and the effect on quality of life of prucalopride versus placebo in subjects aged 18 years and older 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 or non-pregnant, non-breastfeeding female out-patient ≥18 years of age (no upper age limit).
2. Subject has a history of constipation. The subject reports an average of ≤2 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 at least a quarter of the
stools;
b) Sensation of incomplete evacuation following at least a quarter of
the stools;
c) Straining at defecation 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/her current laxative treatment and is willing to use rescue medication according to the rescue rule [bisacodyl (Dulcolax®)/enemas]
Main inclusion criteria to be assessed at randomisation:
1. During the run-in phase the subject reports an average of ≤2 SBM/week that result in a feeling of complete evacuation (SCBM).
2. Subject stopped his/her laxative treatment and did not use rescue mediation on more than 75% of days during the run-in phase.
3. Subject did not use disallowed medication during the run-in phase.
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E.4 | Principal exclusion criteria |
Main exclusion criteria to be assessed at screening:
1. Subjects in whom constipation is thought to be drug-induced
2. Subjects using any disallowed medication.
3. Subjects who previously used prucalopride.
4. 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 endpoint is defined as the proportion (%) of subjects with an average of ≥3 SCBM/week evaluated over the 24-week treatment phase. |
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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:
- The proportion of subjects with an average increase of ≥1 SCBM/week.
- The average number of (SC)BM/week and change from baseline.
- The 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) and % (SC)BM with hard/very hard consistency (Type 1 or 2 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.
- 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 on Day 28 (Week 4).
- Average number of bisacodyl (Dulcolax®) tablets taken per week and the 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 gastrointestinal 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).
Quality of life data measured at scheduled visits will be analysed by each scheduled visit and at endpoint. For all scores, summary statistics, will be provided as well as tabulations showing the percentage of subjects with an average improvement of ≥ 1 point.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary parameters in category A will be derived from the e-diary and evaluated over the 24-week treatment period as well as after 4 weeks of treatment and per 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 | No |
E.6.13 | Others | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |