Efficacy and Safety of Mebeverine + Simethicone in Patients With Functional Bowel Disorders
Condition: Functional Bowel Disorder
MeSH terms: Intestinal Diseases; Gastrointestinal Diseases
Intervention: Mebeverine+Simethicone; Mebeverine; Simethicone
Intervention description: fixed-dose combination, film-coated tablets, 135 mg + 80 mg; Duspatalin®, coated tablets 135 mg; Espumisan® capsules 40 mg
Intervention MeSH terms: Mebeverine; Simethicone; Alverine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 465.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Mebeverine+Simethicone; Duspatalin; abdominal pain; bloating/flatulence; functional bowel disorder; fixed dose combination; NRS11

Summary:

      The parallel three-group study of efficacy and safety was planned to investigate the
      reduction in abdominal pain and bloating during treatment with the fixed-dose combination of
      Mebeverine + Simethicone versus Duspatalin® and Espumisan® as a monotherapy (Protocol No.
      MESI3001).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Informed Consent Form;

          2. Males and females aged 18 to 75 years old (inclusive);

          3. Abdominal pain and bloating/flatulence due to functional bowel disorder (including
             IBS, chronic functional constipation, chronic functional diarrhea or functional
             abdominal bloating);

          4. Episodes of abdominal pain for at least 3 months, with a frequency of at least 3 times
             a month;

          5. Abdominal pain intensity of 4 to 9 points (inclusive) when assessed on the NRS-11
             scale (i.e. weekly average, with daily recording of the worst pain for the last 24
             hours during last week of Screening and Run-in period);

          6. Bloating/flatulence intensity of of 4 to 9 points (inclusive) when assessed on the
             NRS-11 scale (i.e. weekly average, with daily recording of the worst bloating episode
             for the last 24 hours during last week of Screening and Run-in period);

          7. Patients' consent to use adequate contraception methods throughout the study. Adequate
             contraception methods include:

               1. oral contraceptives or contraceptive patches,

               2. condom or diaphragm (barrier method) with spermicide, or

               3. an intrauterine device

        Exclusion Criteria:

          1. Hypersensitivity to mebeverine, simethicone, drotaverine, excipients of the studied
             products, or contraindications;

          2. Intake of tricyclic antidepressants, eluxadoline, linaclotide, selective serotonin
             re-uptake inhibitors, rifaximin, lubriprostone within the last week before screening;

          3. New prescription or any change in probiotic drug therapy (including change in the drug
             or dosage regimen) during the last month before screening;

          4. History of intestinal obstruction, stricture, toxic megacolon, GI (gastro-intestinal)
             perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic
             colitis, or impaired intestinal circulation (e.g. aorto-iliac disease);

          5. History of major gastric, hepatic, pancreatic or intestinal surgery (appendectomy,
             hemorrhoidectomy, or polypectomy allowed as long as occurred > 3 months prior to trial
             screening; uncomplicated laparoscopic or open cholecystectomy is allowed if no history
             of post-operative biliary tract pain and surgery occurred > 3 months prior to
             screening);

          6. Significant and progressive enlargement of the liver, spleen, lymph nodes; ascites;
             palpable tumor formation in the abdominal cavity / pelvis according to physical
             examination, hepatic cirrhosis;

          7. Significant concomitant acute or chronic disease (cardiovascular, gastrointestinal,
             endocrine, immunological, metabolic, bronchopulmonary, urinary system) or any
             condition that, according to Investigator, is a contraindication for the patient to
             participate in the study if interference with the study performance;

          8. Any inflammatory bowel disease (Crohn's disease, ulcerative colitis, any infection
             including bacterial, viral, protozoa, helminthosis);

          9. Elevated fecal calprotectin level 1 month before or at screening which indicates the
             presence of inflammatory GIT disease;

         10. Unexplained GI bleeding within 3 months prior to screening;

         11. Confirmed diagnosis of bile acids malabsorption;

         12. History of any malignant disease except basal cell carcinoma of skin and vesical
             cervix carcinoma in situ which were cured ≥ 5 years ago;

         13. Confirmed diagnosis of celiac disease;

         14. Confirmed hereditary galactose or fructose intolerance , total lactase deficiency,
             sucrase-isomaltose insufficiency, glucose-galactose malabsorption syndrome;

         15. Diet changes (e.g, switching to fermented foods, a gluten-free diet) within the 1
             months prior to screening;

         16. Planned elective surgery during the study;

         17. Pancreatic exocrine insufficiency or acute pancreatitis;

         18. Endometriosis in women;

         19. Positive results of tests for HIV, hepatitis B or C, at the moment of screening;

         20. Drugs or alcohol abuse at screening or in the past, which, in the Investigator's
             opinion, makes the patient not eligible for participation in the study;

         21. Participation in another clinical study or another study drug administration within 30
             days prior to screening;

         22. Pregnant or lactating women, or women planning to get pregnant during the clinical
             study; women of child-bearing potential (including those without history of surgical
             sterilization and women with <2 years post-menopause) not using adequate contraception
             methods;

         23. Inability to read or right; unwillingness to understand and comply with Protocol
             procedures; non-compliance with medication dosing regimen or procedures which, in the
             Investigator's opinion, may affect study results or the patient's safety and prevent
             the patient's participation in the study; any other concomitant diseases or severe
             mental disorders, which make the patient ineligible for study participation, limit the
             legal basis for Informed Consent procedure, or may affect the patient's ability to
             participate in the study.