E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
opioid induced constipation in subjects with chronic non-cancer pain |
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E.1.1.1 | Medical condition in easily understood language |
Constipation induced by opioid intake for chronic non-cancer pain |
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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 efficacy of prucalopride versus placebo over 12 weeks of treatment in subjects aged 18 years and older with chronic non-cancer pain, suffering from OIC. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of prucalopride in subjects aged 18 years and older with chronic non-cancer pain, suffering from OIC.
To document the plasma concentrations of prucalopride in subjects aged 18 years and older with chronic non-cancer pain, suffering from OIC. |
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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 chronic pain of any aetiology (except cancer pain) requiring daily maintenance treatment with opioids; has been on a stable daily opioid dose during at least the previous 2 weeks; and is expected to remain on a stable daily dose of opioids for at least 15 weeks after Visit 1.
3. Subject is suffering from OIC (i.e. secondary to chronic opioid use), which is defined as having an average of ≤2 SBM/week and one or more of the following symptoms that started after initiating opioids:
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. bowel movements 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.
4. Subject agrees to stop his/her current laxative treatment and is willing to use rescue medication according to the rescue rule [Dulcolax® (bisacodyl)/ enemas].
Main inclusion criteria to be assessed at baseline (randomisation):
1. Subject has been taken a stable maintenance dose of opioids during the run-in period.
2. Subject is constipated, i.e. had an average of ≤2 SBM/week during the run-in period.*
3. Subject stopped his/her laxative treatment and did not use rescue mediation on more than 75% of days of the run-in period.*
4. Subject did not use disallowed medication during the run-in period.
* Excluding the first 7 days for subjects using medication influencing bowel habit. |
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E.4 | Principal exclusion criteria |
1. Constipation is thought to be drug-induced (except for opioids).
2. Disallowed medication is being used.
3. Subject was on chronic therapy for chronic constipation prior to the start of opioid therapy.
4. Subject is suffering from secondary causes of chronic constipation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion (%) of subjects with an average weekly frequency of at least 3 SBM/week (i.e. a responder) over the 12-week treatment period.
A minimum of 28 days with e-diary data has to be present for a valid derivation of the primary endpoint. If less e-diary data are present the subject will be considered a non-responder. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
over the 12-week treatment period |
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E.5.2 | Secondary end point(s) |
-The proportion (%) of subjects with an increase of ≥1 (spontaneous complete) bowel movement [(SC)BM]/week over the entire treatment period.
- Average number of (SC)BM/week and change from baseline.
- Number of (SC)BM/week: descriptive statistics and distribution in categories: 0, (0;1), [1;2); [2;3), [3;→).
- Consistency per (SC)BM: descriptive statistics of 5-point score
- Straining per (SC)BM: descriptive statistics of 5-point score
- Sensation of complete evacuation per (S)BM: % (S)BM with sensation of complete evacuation.
- Average time to first (SC)BM after intake of the trial medication on Day 1 and on Day 29.
- Average number of Dulcolax® (bisacodyl) tablets taken per week and the average number of days with laxatives per week.
The following scales will be summarised by descriptive statistics and by tabulations of proportions of subjects with an increase of ≥1 point:
- Subject’s global assessment of severity of constipation.
- Subject’s global assessment on efficacy of treatment.
- PAC-SYM total, subscale and individual item scores.
- PAC-QOL total, subscale and individual item scores. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
bowel movement and intake of bisacodyl over the 12-week treatment period questionnaires / evaluations at weeks 0, 4, 12 |
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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 | Yes |
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 | 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) | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |