Diarrhoea-predominant irritable bowel syndrome (IBS-D) MedDRA version: 20.1 Level: PT Classification code 10023003 Term: Irritable bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
Cosmo Technologies Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: signed written informed consent before inclusion in the study 2. Sex and Age: males/females, =18 year old 3. IBS diagnosis: confirmed IBS-D diagnosis per Rome IV criteria 4. Symptoms: active symptoms of IBS at baseline (day 1) as measured by average daily scores for at least 7 days before baseline during the period from Day -14 to Day -1: a. abdominal pain score =3 using an 11-point numeric rating scale and b. bloating score: 2-4* inclusive and c. stool consistency: score 6 or 7 (Bristol stool form scale) for at least 2 days from day -7 to day -1 and by a negative response to the global IBS symptom assessment question and to the IBS-related bloating assessment question both given weekly during the screening phase up to day 1 before randomisation: d. "In the past 7 days, have you had adequate relief of your IBS symptoms?" [No] and e. "In the past 7 days, have you had adequate relief of your IBS symptom of bloating?"[No] 5. Colonoscopy: performed within 5 years; if patient’s age >50, colonoscopy performed within 2 years 6. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the study 7. Literacy: sufficiently literate to comply with the study requirement of using and filling diaries 8. Contraception and fertility: females of childbearing potential and fertile males must be using at least one reliable method of contraception. Reliable methods of contraception for women include: a. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit b. A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit Reliable methods of contraception for men and male partners of female patients include: c. Male condoms with spermicide Reliable methods of contraception for both women and men include: d. A sterile sexual partner or sexual abstinence Women of non-childbearing potential or in post-menopausal status for at least 1 year and sterile or surgically sterilised men will be admitted. For women of childbearing potential, serum pregnancy test result must be negative at screening *in case of an average value>4 , values =4.49 will be admitted Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 272 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1. IBS: symptoms of constipation at baseline evaluated during the period from Day -14 to Day -1: a. less than 3 bowel movements a week and b. stool consistency score =2 for =2 days in a week 2. Screening phase: failure to record the daily symptom assessments in the diary cards for at least 7 days before baseline 3. Gastroenteric: underlying gastrointestinal diseases including ulcerative colitis, Crohn’s disease, pancreatitis, any active infectious, haemorrhagic or inflammatory disorder not related to IBS-D, gastrointestinal motility disorders such as ileus, gastroparesis or pseudoobstruction, gastroduodenal ulcer, gastrointestinal malignancy or potentially fatal diseases if not full in remission (5 years from diagnosis and without maintenance treatment), amyloidosis and cholelithiasis if cholecystectomy not performed 4. Intolerance: ascertained underlying lactose intolerance with response to diet or any other malabsorption syndrome with the exclusion of asymptomatic lactose malabsorption 5. Coeliac disease: ascertained or presumptive underlying coeliac disease 6. Bile: ascertained or presumptive bile acid malabsorption or bile acid induced diarrhoea 7. Diabetes: underlying diabetes type I or II 8. Thyroid: abnormal thyroid function not controlled by thyroid medications 9. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study 10. Renal function: ascertained or presumptive clinically significant renal insufficiency or creatinine above twice the upper limit of normal (ULN) of the performing laboratory reference range 11. Liver function: chronic liver disease or clinically significant liver enzyme abnormality as evidenced by elevated AST, ALT or total bilirubin >1.5 times ULN 12. AIDS/HIV: ascertained or presumptive acquired immunodeficiency (AIDS) or known infection with human immunodeficiency virus (HIV) 13. Diseases: significant history of medical or surgical conditions excluding hysterectomy, caesarean section, appendectomy, cholecystectomy, benign polypectomy and inguinal hernia and including renal, hepatic, cardiovascular, haematological, endocrine, immune, psychiatric or neurological diseases that in the investigator’s opinion may interfere with the aim of the study; malignant diseases not in remission for at least 5 years 14. Medications: alosetron, eluxadoline, ondansetron, tegaserod, lubiprostone, warfarin, antipsychotic, antispasmodic, prokinetic, antidiarrhoeal, laxative, probiotic, narcotic or antibiotic agents within 14 days before the screening visit; antidepressant agents of the selective serotonin-reuptake inhibitor and tricyclic classes unless taken at a stable dose for at least 6 weeks before the screening visit. Once-off medications related to the preparation or performance of the colonoscopy should be recorded as concomitant medications but are not exclusionary. 15. Investigational drugs: participation in the evaluation of any investigational product within 30 days before this study 16. Drug and alcohol: known history of drug or alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2015] abuse 17. Pregnancy (females only): pregnant or lactating women or wishing to become pregnant in the 3 months following this visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare two dose regimens of Rifamycin SV-MMX® 600 mg tablets versus matching placebo in terms of proportion of subjects with adequate relief of the composite of abdominal pain and stool consistency;Secondary Objective: Secondary objective is to evaluate the safety and tolerability of Rifamycin SV-MMX® 600 mg tablets, two and three times daily, in subjects with diarrhoea-predominant irritable bowel syndrome.;Primary end point(s): Proportion of weekly responders defined as subjects who weekly have relief of the composite of abdominal pain and stool consistency, on the basis of their daily assessments. Relief of abdominal pain is defined as a decrease in the weekly average of abdominal pain score of at least 30% compared with baseline and relief of stool consistency is defined as a 50% or greater reduction in the number of days per week with at least one stool that has a consistency of Type 6 or 7 compared with baseline.;Timepoint(s) of evaluation of this end point: 12 weeks or last timepoint of patient data collection (in case of early discontinuation). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Proportion of subjects with adequate relief of global IBS symptoms for at least 2 (consecutive or not) of the 10 weeks during the follow-up period (i.e., weeks 3 through 12). Adequate relief of global IBS symptoms is defined as a response of "yes" to the following question, which will be asked weekly (every 7 days): "In regard to all your symptoms of IBS, as compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptoms? [Yes/No]" 2) Proportion of subjects with adequate relief of global IBS symptom during at least 2 weeks (consecutive or not) per month (“monthly response”) during month 1, during month 1 through 2 and during month 1 through 3 will be assessed to identify the onset and duration of the therapeutic effect. 3) Proportion of subjects with adequate relief of IBS-related bloating for at least 2 (consecutive or not) of the 10 weeks during the follow-up period (i.e., weeks 3 through 12). Adequate relief of bloating is defined as a response of "yes" to the following question, which will be asked weekly (every 7 days): "In regard to your symptom of bloating, as compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptom of bloating? [Yes/No]." 4) Proportion of subjects with adequate relief of bloating during at least 2 weeks (consecutive or not) per month (“monthly response”) during month 1, during month 1 through 2, and during month 1 through 3 will be assessed to identify the onset and duration of the therapeutic effect. 5) Proportion of subjects with relief (weekly responders) determined from the subjects’ daily assessments of IBS symptoms, bloating, and abdominal pain; relief of IBS symptoms and bloating is defined as a score of either 0 (not at all) or 1 (hardly) for at least 50% of the days in a given week or a score of 0 (not at all), 1 (hardly), or 2 (somewhat) for 100% of the da | — |
Countries
Belgium, Germany, Spain
Contacts
Public ContactDIEGO SCANNIFFIO
CROSS Research S.A
Outcome results
None listed