E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Irritable Bowel Syndrome (IBS) with recurrent abdominal pain or discomfort according to ‘S3 Guideline and Rome III criteria’ |
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E.1.1.1 | Medical condition in easily understood language |
Gastrointestinal disorders |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048571 |
E.1.2 | Term | Irritable bowel syndrome aggravated |
E.1.2 | System Organ Class | 100000016754 |
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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 investigate the effectiveness of oral treatment with Pro-Symbioflor® in patients with irritable bowel syndrome compared to placebo in the improvement of the frequency and severity of IBS symptoms. To determine the safety and tolerability of Pro-Symbioflor® |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female outpatients aged ≥18 years • Diagnosis of irritable bowel syndrome according to Rome III and the current ‘German S3 guideline on IBS 2011’ issued by the relevant German medical associations: 1. Recurrent abdominal pain (e.g. discomfort, bloating) at least 3 days per month in the last 3 months associated with 2 or more of the following criteria - Improvement with defecation -Onset associated with a change in frequency of stool -Onset associated with a change in form(appearance) of stool 2. Significant reduction in the quality of life as per patient’s estimation 3. Symptom related exclusion of relevant differential diagnoses 4. Patient seeks medical help because of gastrointestinal symptoms • IBS symptom onset ≥ 6 months • Colonoscopy with no clinically relevant findings (≤ 3 years) • Female patients of childbearing potential must be either surgically sterilized or use highly effective contraception at least 3 months prior to enrolment with a negative pregnancy test at screening, baseline/day 0 • No changes in the dose of selective serotonin reuptake inhibitors (SSRI), if applicable, 30 days prior to screening • Willingness to refrain from significant changes in diet, fibre intake, fluid intake, or physical activity during trial participation • Willingness to refrain from the use of other medications for IBS treatment, including probiotic medication • Ability to comply with treatment • Sufficient knowledge of German language to understand trial instructions and rating scales • Written informed consent prior to enrolment |
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E.4 | Principal exclusion criteria |
• History of abdominal surgery within the 6 months prior to screening • Presence or suspected presence of unstable coronary artery disease, untreated organic gastrointestinal disease and uncontrolled metabollic diseases causing IBS-related symptoms or collagen vascular disease within the 6 months prior to screening • Lactose intolerance (in doubtful cases, a diagnostic test has to be performed) • Abnormal endoscopy/ abdominal ultrasound requiring further investigation • Any alarm symptoms including uninvestigated anaemia, rectal bleeding, weight loss, or unresolved fever within the 6 months prior to screening • Participation in another clinical trial or use of any investigational drug within 30 days before dosing • Evidence of current or recent alcohol or drug abuse within 6 months prior to screening • History or evidence of current laxative abuse • Continuous abdominal pain for more than 4 hours before bowel movements • Pregnancy or breast feeding • Any illness or condition that might impact the safety of study drug administration or evaluability of drug effect based on Investigator’s discretion • No consent to recording and processing of pseudonymised data according to legal requirements • Patients who are committed to a clinic or similar institution by official or judicial order Patients will be excluded from randomization to a treatment group if they have/are: • Current intake of prohibited medications (e.g. spasmolytics, analgesics, laxatives, antidiarrhoeals and probiotic medication) exept for rescue purposes • Serum potassium, magnesium, or calcium values outside the normal range at screening and clinically significant • Serum aspartate transaminase (AST), alanine transaminase (ALT), or gamma glutamyltransferase (GGT) ≥3 times the upper limit of the normal range at screening or baseline, or a bilirubin value ≥2 times the upper limit of the normal range at screening • Abnormal thyroid stimulating hormone (TSH) value at screening, unless the free T4 value is normal; (Note: Levothyroxine will be allowed, if on stable dose for at least 30 days prior to screening and no changes expected during study) • Any laboratory value(s) outside the laboratory reference range at screening considered clinically significant by the Investigator • Positive stool culture at screening in patients with diarrhoea-predominant IBS
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E.5 End points |
E.5.1 | Primary end point(s) |
Response will be assessed by two primary endpoints 1. Response rate measured by the IBS Global Assessment of Improvement Scale (IBS-GAI). IBS-GAI response is defined as at least 50% moderate or substantial improvement on the 7-point rating scale during the 26 weeks of treatment and the last four weeks. 2. Response rate measured by the 11-point numeric rating scale (NRS). Abdominal Pain Intensity response is defined as a decrease in the weekly average of worst abdominal pain of at least 30% compared to baseline for a minimum of 13 of the 26 measurements and for at least two of the last four weeks (i.e. at least 50% improvement of Abdominal Pain Intensity during the 26 weeks of treatment) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 26 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Efficacy • Response rate measured by the 7-point IBS Global Assessment of Improvement Scale (IBS-GAI) during the 26 weeks of treatment. Response is defined as at least 75% moderate or substantial improvement or 50% improvement and no worsening during the last 4 weeks of treatment • Response rate measured by the 11-point numeric rating scale during the 26 weeks of treatment. Response is defined as ≥30% improvement in Abdominal Pain Intensity weekly response compared to baseline for a minimum of 20 of the 26 measurements (i.e. 75% improvement of Abdominal Pain Intensity) or 50% improvement and no worsening during the last 4 weeks of treatment • Response rate measured by the 11-point numeric rating scale during the 26 weeks of treatment. Response is defined as ≥ 40 % improvement in Abdominal Pain Intensity weekly response compared to baseline for a minimum of 13 of the 26 measurements and for at least two of the last four weeks • Change from baseline of the IBS specific Quality of Life questionnaire (IBS-QOL) • Change from baseline of the EQ-5D questionnaire • Stool frequency / week • Number of days with straining during a bowel movement / week • Number of days with imperative urge to defecate / week • Number of pain-free days / week Safety: • Adverse events • Vital signs • Laboratory values |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 26 weeks of treatment |
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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 | Yes |
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 | 30 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |