Safety and Efficacy of Rifaximin in Patients With Papulopustular Rosacea and Positive Lactulose Breath Test

Key inclusion Criteria: 1. Men and women aged 18 to 70 years at screening. 2. Female participants are eligible if they are either of non-childbearing potential or of childbearing potential with a negative pregnancy test result at screening and randomization and agreeing to use a highly effective method of contraception until 72 hours after taking the last study treatment dose. 3. Moderate-to-severe papulopustular rosacea (a.k.a. subtype II, RII) at screening and confirmed at randomization. Moderate-to-severe rosacea is defined as the presence of 11 or more facial papules or pustules with or without plaques. 4. Positivity of lactulose H2/CH4 breath test (L-BT) within the last 2-weeks before randomization. 5. Patients accepting to provide and legally capable of providing free and informed consent to all procedures included in the protocol (including facial skin photography). Key exclusion Criteria: 1. Granulomatous rosacea or rosacea fulminans. 2. Erythematoteleangectatic, phymatous or ocular rosacea only. Patients with these subtypes associated with papulopustular rosacea can be enrolled. 3. Circulating anti-helicobacter pylori IgM and/or IgG at screening (V1). 4. Positivity at the faecal Clostridium Difficile toxin assay at screening (V1). 5. History or family history of inflammatory bowel disease (Crohn's disease or ulcerative colitis) or other conditions characterized by severe intestinal ulcers. 6. History or family history of coeliac disease. 7. Patients with intestinal obstruction or partial intestinal obstruction. 8. Presence of diarrhoea associated with fever and/or blood in the stool. 9. Health conditions requiring continuous or intermittent treatment with facial topical, inhaled or systemic steroids and/or biologic or non-biologic immunosuppressive or immunomodulatory agents (e.g. autoimmune diseases, etc.). 10. Severe kidney impairment (i.e. estimated glomerular filtration rate \<30 ml/min). 11. Severe hepatic impairment (i.e. Child-Pugh B or C). 12. Cancer or any cancer-related treatment within 5 years prior to screening (excluding non-melanoma skin-cancer). 13. History of alcohol or drug abuse within a year prior to screening. 14. Facial skin conditions that can interfere with reliable assessment of rosacea throughout the study (e.g. keloids, hypertrophic scarring, recent facial surgery etc.) 15. Any other significant health condition (e.g. cardiovascular, respiratory, renal, hepatic, neurologic, psychiatric, hematologic, oncologic, immune etc.) that in the investigator's judgement may: i) jeopardize the patient's safe participation in the trial or ii) make unlikely the patient's completion of the study or iii) make unlikely the patient's compliance with the study procedures (e.g. highly anticipated need of non-permitted treatments, terminal illness, etc.). 16. History of hypersensitivity to rifaximin, rifamycin-derivatives, any of the rifaximin-EIR excipients, or any UV protection cream component. 17. Treatment with biologic immunomodulatory and/or immunosuppressive drugs (e.g. anti-TNF drugs) within 6 months prior to randomization. 18. Treatment with non-biologic immunomodulatory and/or immunosuppressive drugs (e.g. cyclosporine, methotrexate etc.) within 30 days prior to randomization. 19. Treatment with warfarin within 14 days prior to randomization. 20. Treatment with niacin within 30 days prior to randomization. 21. Topical facial or systemic antibiotics within 30 days before randomization; 22. Treatment with neomycin or other low-absorbable oral antibiotics (such as marketed rifaximin) within 90 days before randomization. 23. Topical facial, inhaled or systemic corticosteroids within 30 days prior to randomization. 24. Topical facial retinoids within 30 days before randomization. 25. Systemic retinoids within 6 months before randomization. 26. Any other topical or systemic treatment for rosacea within 30 days before randomization (including also laser and pulsed light, etc.). 27. Pharmaceutical prebiotics and probiotics (functional food is allowed), within 30 days before randomization. 28. Any experimental treatment within 6 months prior to randomization. 29. Women who are pregnant, breast-feeding or planning a pregnancy during the trial period.