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 | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
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 | 10023003 |
E.1.2 | Term | Irritable bowel syndrome |
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 assess the effect of mesalazine (Asacol®) treatment compared to placebo on IBS symptoms. |
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E.2.2 | Secondary objectives of the trial |
To assess mesalazine (Asacol®) treatment compared to placebo regarding:
1) Inflammatory mediators measured by the Mucosal Patch Technology 2) Effects on immune cells and cytokines in mucosal biopsies 3) Calprotectin levels in faeces 4) Individual IBS symptom parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Males and females aged 18 to 70 years, both inclusive 2) Subject is diagnosed with irritable bowel syndrome (IBS) prior to Screening based on the Rome III diagnostic criteria for IBS 3) Subject presents with IBS symptom intensity of at least moderate level; defined as an IBS Severity Scoring System (IBS-SSS) score of ≥175 at both Screening and Baseline 4) Provision of signed informed consent |
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E.4 | Principal exclusion criteria |
1) Subjects who are unable to understand the written and verbal instructions 2) Presence of a systemic inflammatory disease 3) Presence of other gastrointestinal diseases likely to explain the IBS symptoms 4) Presence of other severe somatic disease 5) Treatment with non-steroidal anti-inflammatory drugs (NSAID), opioid analgetics or acetylsalicylic acid (ASA) compounds within 7 days prior to Screening 6) Treatment with systemic antibiotics within 28 days prior to Screening 7) Treatment with immunosuppressant drugs within 28 days prior to Screening 8) Other significant medical treatment, which, in the opinion of the investigator, may compromise the safety and efficacy objectives of the study, within 28 days prior to Screening 9) Previously confirmed allergy towards ASA or mesalazine 10) Presence of renal disease and/or concomitant treatment with medications with potential renal side effects 11) Current ongoing infection 11) History of, or current, drug or alcohol dependence 12) Pregnant or lactating women 13) Subjects suspected not to follow instructions based on the discretion of the Investigator 14) Current participation in other intervention studies 15) Female subjects of childbearing potential unwilling to use adequate contraceptive measures throughout the duration of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be an assessment of mesalazine (Asacol®) treatment compared with placebo on IBS symptoms. The main measurement parameters of symptom alleviation will be a global symptom score showing satisfactory symptom relief ≥50% of the time adequate symptoms relief >50% of the time, as as recorded on a weekly basis in a separate questionnaire for the duration of the treatment period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy variable will be measured through weekly assessments of satisfactory symptom relief as evaluated by the patient from the start of treatment (week 0) up until the end of treatment (week 8) |
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E.5.2 | Secondary end point(s) |
Secondary efficacy variables will be assessments of mesalazine (Asacol®) treatment compared to placebo regarding:
1. IBS-symptom severity scale (IBS-SSS) 2. Inflammatory mediators measured by the Mucosal Patch Technology (MPT), e.g. neutrophil mediators, eosinophilic mediators, mast cell activity mediators and cytokines 3. Effect on immune cells and cytokines in mucosal biopsies 4. Levels of calprotectin in foeces 5. Individual symptom parameters in IBS-SSS and the IBS diary 6. Exploratory responder variables: a. satisfactory symptom relief ≥75% of the time b. reduction in IBS-SSS ≥50 at end of treatment compared to randomization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
IBS-SSS will be evaluated on a biweekly basis for the entire duration of the treatment period (Week 0 to Week 8) with one final evaluation performed during the follow-up phase (Week 10). At each timepoint, the IBS-SSS as a whole and individual parametres will be compared against baseline.
Inflammatory mediators, levels of calprotectin in foeces, effect on immune cells and cytokines in mucosal biopsies will be measured as change from baseline (Week 0) at the end of the treatment period (Week 8).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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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The end of the trial will be defined as the timepoint when the last patient in the study completes the final follow-up visit at Week 10 in the study. This is given that no reasons for unscheduled visits going beyond this timepoint will exist for any patients. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |