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Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.
Antimicrob Agents Chemother. 2015 Oct; 59(10):6266-73.AA

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+Show Affiliations

University of Calgary, Calgary, Alberta, Canada thomas.louie@albertahealthservices.ca.Karolinska Institute, Stockholm, Sweden.Talbot Advisors, Anna Maria, Florida, USA.Leeds General Infirmary, Leeds, United Kingdom.Loyola University, Maywood, Illinois, USA.Idaho Falls Infectious Diseases, Idaho Falls, Idaho, USA.Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.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.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26248357

Citation

Louie, Thomas, et al. "Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients With Clostridium Difficile Infection." Antimicrobial Agents and Chemotherapy, vol. 59, no. 10, 2015, pp. 6266-73.
Louie T, Nord CE, Talbot GH, et al. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection. Antimicrob Agents Chemother. 2015;59(10):6266-73.
Louie, T., Nord, C. E., Talbot, G. H., Wilcox, M., Gerding, D. N., Buitrago, M., Kracker, H., Charef, P., & Cornely, O. A. (2015). Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection. Antimicrobial Agents and Chemotherapy, 59(10), 6266-73. https://doi.org/10.1128/AAC.00504-15
Louie T, et al. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients With Clostridium Difficile Infection. Antimicrob Agents Chemother. 2015;59(10):6266-73. PubMed PMID: 26248357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection. AU - Louie,Thomas, AU - Nord,Carl Erik, AU - Talbot,George H, AU - Wilcox,Mark, AU - Gerding,Dale N, AU - Buitrago,Martha, AU - Kracker,Hilke, AU - Charef,Pascal, AU - Cornely,Oliver A, Y1 - 2015/07/27/ PY - 2015/03/02/received PY - 2015/07/20/accepted PY - 2015/8/7/entrez PY - 2015/8/8/pubmed PY - 2016/6/16/medline SP - 6266 EP - 73 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 59 IS - 10 N2 - 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.). SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/26248357/Multicenter_Double_Blind_Randomized_Phase_2_Study_Evaluating_the_Novel_Antibiotic_Cadazolid_in_Patients_with_Clostridium_difficile_Infection_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=26248357 DB - PRIME DP - Unbound Medicine ER -