Diarrhoea-predominant irritable bowel syndrome with recurrent abdominal pain according to Rome IV criteria
Conditions
Interventions
Trade Name: Symbioflor® 2
Pharmaceutical Form: Oral drops, suspension
INN or Proposed INN: Escherichia coli DSM 17252
Current Sponsor code: Escherichia coli DSM 17252
Other descriptive name: Escheric
Sponsors
SymbioPharm GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female outpatients aged =18 years • Diagnosis of irritable bowel syndrome according to Rome IV: 1. Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months associated with two or more of the following criteria: - Related to defecation - Associated with a change in frequency of stool - Associated with a change in form (appearance) of stool 2. Criteria fulfilled for the last 3 months and 3. IBS symptom onset = 6 months 4. IBS-D subtype with abnormal stools being usually diarrhoea • Colonoscopy with no clinically relevant findings (performed for all patients younger than 50 years and for patients =50 years of age within the last 5 years) • Female patients of childbearing potential must be either surgically sterilized or use a highly effective method of contraception with a negative pregnancy test at screening and baseline/day 0 • Willingness to refrain from significant changes in diet, fibre intake, fluid intake, or physical activity during the study • 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 • Email account and internet access available The patients will only be randomised to either treatment or control group if they meet the following criteria: • Mean abdominal pain intensity = 3 on the 11-point NRS scale during the last 14 days • Loose or watery stools = 25% and hard or lumpy stools in =65 years) yes F.1.3.1 Number of subjects for this age range 84
Exclusion criteria
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 metabolic diseases causing IBS-related symptoms, or collagen vascular disease within the 6 months prior to screening • Lactose or fructose intolerance explaining the symptoms (in doubtful cases, a diagnostic test has to be performed) • Coeliac disease (in doubtful cases, a diagnostic test has to be performed) • Confirmed bile acid malabsorption by SeHCAT-Test or successful treatment by bile acid sequestrant • Change of diet e.g. FODMAP, gluten-free within last 3 months • 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 or 5 half-lives (whichever is longer) before dosing • Evidence of current or recent alcohol or drug abuse within 6 months prior to screening • History or evidence of current laxative abuse • 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 discretionNo 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 • Hypersensitivity to active ingredient or any excipients of the medicinal product Patients will be excluded from randomization to a treatment group if they have/are: • Current intake of prohibited medications except for rescue purposes (refer to 10.3) • 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 further laboratory value(s) outside the laboratory reference range at screening considered clinically significant by the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effectiveness of oral treatment with Symbioflor®2 in patients with IBS-D compared to placebo in the improvement of the frequency and severity of IBS-D symptoms To determine the safety and tolerability of Symbioflor®2 ;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint is a combined endpoint containing two co-primary components to assess efficacy, namely Bristol Stool Scale and Abdominal Pain Intensity. A statistically significant change must be found in the combined endpoint. An overall responder for the combined primary endpoint is defined as a patient, who is classified as a BSS responder as well as an Abdominal Pain Intensity responder. First component of the combined primary efficacy endpoint: Response rate measured by Bristol Stool Scale. BSS response is defined as at least 50% reduction in the number of days with at least one stool that has a consistency of 6 or 7 per week compared to baseline for a minimum of 13 of the 26 measurements (i.e. at least 50% improvement of stool consistency during treatment). Second component of the combined primary efficacy endpoint: 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 (i.e. at least 50% improvement of Abdominal Pain Intensity during treatment). ;Timepoint(s) of evaluation of this end point: after 26 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy (see 14.6.3.2): • Response rate measured by the 7-point IBS Global Assessment of Improvement Scale (IBS-GAI) during the 26 weeks of treatment. IBS-GAI response is defined as at least 50% moderate or substantial improvement during the 26 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 • Change from baseline of Abdominal Pain Intensity mean score • IBS-GAI weekly mean score • Change from baseline in IBS severity with IBS-SSS. • 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 imperative urge to defecate / week • Number of pain-free days / week Subgroup analyses • Effectiveness of Symbioflor®2 by gender (male/female) • Effectiveness by severity (mild, moderate) Safety: • Adverse events • Vital signs • Laboratory values;Timepoint(s) of evaluation of this end point: after 26 weeks of treatment | — |
Countries
Germany
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services GmbH
Outcome results
None listed