A multi-center, randomized, double-blind study to compare the efficacy and safety of cadazolid versus vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD)

INTERVENTION: Product Name: Cadazolid Product Code: ACT‐179811 Pharmaceutical Form: Granules for oral suspension in sachet INN or Proposed INN: Cadazolid Current Sponsor code: ACT‐179811 Other descriptive name: Cadazolid Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Pharmaceutical form of the placebo: Granules for oral suspension Route of administration of the placebo: Oral use Trade Name: Vancocin Pharmaceutical Form: Capsule, hard INN or Proposed INN: VANCOMYCIN CAS Number: 1404‐90‐6 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 125‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Clostridium difficile‐associated diarrhea (CDAD) ; MedDRA version: 19.0 Level: PT Classification code 10054236 Term: Clostridium difficile infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: To determine whether the clinical response after 10‐day oral; administration of cadazolid is non‐inferior to oral vancomycin; in subjects with CDAD. Primary end point(s): Clinical Cure defined as:; • Resolution of Diarrhea (ROD: = 3 UBMs per day for at least 2 consecutive days) on study treatment, maintained for 2 days after End of Treatment (EOT); AND; • No additional antimicrobial treatment active against CDAD or FMT between first dose and 2 days after EOT (inclusive).; Secondary Objective: To determine whether oral administration of cadazolid for; 10 days is superior to oral vancomycin in the sustained clinical; response of subjects with CDAD.; To determine whether the resolution of diarrhea (ROD) is; more rapid with oral administration of cadazolid compared to; vancomycin.; To determine whether CDAD symptoms, as reported by the; subject, show larger improvements from baseline with oral; administration of cadazolid compared to vancomycin. Timepoint(s) of evaluation of this end point: See above SECONDARY OUTCOME: Secondary end point(s): Sustained Cure defined as: ; • Clinical Cure ; AND ; • No Recurrence ; Recurrence is defined for subjects with Clinical Cure as: ; • New episode of diarrhea (NED: > 3 UBMs within 1 day) occurring between 3 days after EOT and Visit 5 ; AND ; • Positive C. difficile GDH and toxin stool test on the same stool sample ; AND ; • Antimicrobial treatment active against CDAD or FMT started between 3 days after EOT and Visit 5 (or participation in the re‐treatment extension with cadazolid). ; ; Time to ROD, defined as: ; • The time (h) elapsed between the first dose of study drug ; and the time when ROD is considered achieved. ; ; Absolute change from baseline in CDAD DaySyms Patient Reported Outcomes (PRO). ; CDAD DaysSyms total daily score change from baseline up to ; Day 12. Timepoint(s) of evaluation of this end point: See above INCLUSION CRITERIA: ‐ Signed Informed Consent. ‐ Male or female = 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception. ‐ Subject with a diagnosis of mild‐moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with > 3 unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile GDH and toxin test on the same stool sample produced within 72 hours prior to randomization. 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 411 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 219