The objective of this study is to evaluate the safety and efficacy Rifamycin SV-MMX® 600 mg tablets for patients with diarrhoea-predominant irritable bowel syndrome when administered two to three times daily.

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:

   1. abdominal pain score ≥3 using an 11-point numeric rating scale and

   2. bloating score: 2-4 inclusive and

   3. stool consistency: score 6 or 7 (measured by the 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:

   4. "In the past 7 days, have you had adequate relief of your IBS symptoms?" [No] and

   5. "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 electronic diaries and filling in electronic forms

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:

1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit

2. 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:

3. Male condoms with spermicide

   Reliable methods of contraception for both women and men include:

4. 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

Exclusion Criteria:

1. IBS: symptoms of constipation at baseline:

   1. less than 3 bowel movements a week and
   2. 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

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

None. IPD not to be shared.