Efficacy and Safety of CB-01-11 200mg Tablets in Infectious Diarrhoea

To assess the safety and the preliminary efficacy data on the three doses of the new Cosmo Technologies oral rifamycin SV colon-release 200 mg tablets manufactured according to MMXTM technology (CB-01-11) in the treatment of infectious diarrhoea.

Primary end points to determine:

• The safety and preliminary efficacy data of the three doses of the new rifamycin SV formulation tested based upon the time elapsed from the ingestion of the 1st dose of study medication to the passage of the last unformed stool (TLUS), in compliance with the relevant guidelines

Secondary end-points to determine:

• The number of patients showing improvement in diarrhoea during a 24-h interval, i.e. >50 % reduction of bowel movements.
• The number of unformed stools passed per 24-h interval, after dosing.
• The number of patients who are declared to be "well". Wellness is defined as the patient having 48 hours with no unformed stools, a maximum of two soft stools and no clinical symptoms of infectious diarrhoea.
• The number of treatment failures. A treatment failure is defined as clinical deterioration or worsening of symptoms or illness continuing after 120 h following the first dose.
• The number and percentage of patients recovered from diarrhoea. Patients were considered to have recovered if fewer than three unformed stools were passed in the previous 24 hours and no symptom of enteric infection were present.

Inclusion criteria

Patients had to meet all of the following inclusion criteria:

• Male and female patients aged 18-65 years inclusive on the date of screening.
• Patients with infectious diarrhoea (ID) in the active phase of no more than 72-h duration. Criteria for diagnosis of ID were: three or more unformed stools in the preceding 24 hours, and at least one symptom of enteric infection e.g. abdominal cramps/pain, tenesmus, urgency, an excess of gas/flatulence, nausea, vomiting.
• If female, and of child-bearing potential, use of an effective contraceptive method. (Oral contraceptives, injectable hormonal contraceptives, double-barrier method (condom/diaphragm with spermicide) and intra-uterine devices, according to the definition of Note 3 of ICH M3(M) Guideline. Females were considered not to be of child-bearing potential, if they were at least 12 months post-menopausal.
• Ability, in the investigator's opinion to comprehend the full nature and purpose of the study, including the possible risks and side effects, and willing to comply with the requirements of the study.
• Patients who have voluntarily signed and dated the informed consent document for screening and study specific procedures.
• Patients must be sufficiently literate to be able to complete a diary card.

Exclusion criteria

Patients had not to have had of any of the following:

• Females of child-bearing potential not using an effective contraceptive method.
• Pregnant or lactating females.
• Fever (defined as a body (axillary) temperature ≥ 38° C) present either at the screening visit or in the previous 24 hours.
• Visible presence of blood in the stool at baseline.
• Patients with any history or evidence on examination, of clinically significant gastrointestinal (in particular intestinal obstruction and severe intestinal ulcerative lesions), renal, hepatic, endocrine, respiratory, cardiovascular, dermatological or haematological disease, which in the opinion of the investigator could affect the interpretation of the efficacy and safety data.
• Patients with moderate or severe dehydration (see Appendix 2 of the protocol, for definitions of clinical symptoms).
• Prohibited previous and concomitant medication (see relevant section of the protocol).
• History of recent gastrointestinal malignancy (within 6 months).
• Allergy: presumptive or ascertained hypersensitivity to the study drug, history of anaphylaxis or allergic reactions in general.
• History of, or current misuse of alcohol, drugs or abuse of medication.
• Participation in another study with any investigational product within 3 months before screening.
• Patients who, in the opinion of the investigator, could be un-cooperative and/or non-compliant and should not therefore participate in the study.