title: Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.
abstract: Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.).
authors.affiliation: University of Calgary, Calgary, Alberta, Canada thomas.louie@albertahealthservices.ca.
authors.forename: Thomas
authors.initials: T
authors.lastname: Louie
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
authors.affiliation: Talbot Advisors, Anna Maria, Florida, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Talbot
authors.affiliation: Leeds General Infirmary, Leeds, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Wilcox
authors.affiliation: Loyola University, Maywood, Illinois, USA.
authors.forename: Dale N
authors.initials: DN
authors.lastname: Gerding
authors.affiliation: Idaho Falls Infectious Diseases, Idaho Falls, Idaho, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Buitrago
authors.affiliation: Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
authors.forename: Hilke
authors.initials: H
authors.lastname: Kracker
authors.affiliation: Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Charef
authors.affiliation: Department of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln, Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D003015:Clostridium Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D003967:Diarrhea / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061214:Patient Safety; D012008:Recurrence; D014640:Vancomycin / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; C000591679:cadazolid; D014640:Vancomycin