Efficacy, Safety and Tolerability of Cadazolid in Subjects With Clostridium Difficile Associated Diarrhea (CDAD)

A Multi-center, Double-blind, Randomized, Active Reference, Parallel Group Study to Evaluate the Efficacy, Safety and Tolerability of a 10-day Twice Daily Oral Administration of Three Doses of Cadazolid (ACT-179811) in Subjects With Clostridium Difficile Associated Diarrhea (CDAD)

Cadazolid is a new antibiotic developed for the treatment of Clostridiun difficile associated diarrhea (CDAD), also known as Clostridium Difficile Infection (CDI). The purpose of the study was to evaluate the efficacy and safety of different doses of cadazolid in order to find the dose of cadazolid to be used for further clinical development of the compound in subjects with CDAD.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Drug: Cadazolid; Drug: Placebo-matching vancomycin; Drug: Vancomycin; Drug: Placebo-matching cadazolid

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N2T8
    • Clinical Ivestigative Site 6602
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Clinical Investigative Site 6605
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Clinical Investigative Site 6601
    • Sherbrooke, Quebec, Canada, J1H5N4
      • Clinical Investigative Site 6606
• Germany
  • Koln, Germany, 50937
    • Clinical Investigative Site 6632
  • Regensburg, Germany, 93042
    • Clinical Investigative Site 6633
  • Ulm, Germany, 89081
    • Clinical Investigative Site 6634
• Italy
  • Busto Arsizio, Italy, 21052
    • Clinical Investigative Site 6734
  • Modena, Italy, 4114
    • Clinical Investigative Site 6735
• Sweden
  • Orebro, Sweden, 70185
    • Clinical Investigative Site 6702
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Clinical Investigative Site 6801
  • York, United Kingdom, YO31 8HE
    • Clinical Investigative Site 6804
• United States
  • Delaware
    • Newark, Delaware, United States, 19718
      • Clinical Investigative Site 6902
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Clinical Investigative Site 6919
    • Orlando, Florida, United States, 32837
      • Clinical Investigative Site 6938
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Clinical Investigative Site 6930
    • Marietta, Georgia, United States, 30060
      • Clinical Investigative Site 6935
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Clinical Investigative Site 6915
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Clinical Investigative Site 6906
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Clinical Investigative Site 6917
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Clinical Investigative Site 6936
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Clinical Investigative Site 6903
  • Texas
    • Houston, Texas, United States, 77030
      • Clinical Investigative Site 6914

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Male or female
• At least 18 years of age
• With a diagnosis of Clostridium Difficile-associated diarrhea (CDAD): first occurrence or first recurrence.

Key Exclusion Criteria:

• Concurrent life threatening condition.
• Immuno-compromised subjects, concomittant immuno-suppresive treatment.
• Concomitant antimicrobial treatment for CDAD.
• Any circumstances or conditions, which, in the opinion of the investigator, would affect full participation of the subject in the study or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadazolid 250 mg; Subjects received 250 mg of reconstituted cadazolid suspension twice daily and one placebo-matching vancomycin capsule four times daily for 10 days	Drug: Cadazolid; Cadazolid, provided as powder (250 mg, 500 mg or 1000 mg) to be reconstituted as a suspension prior to oral administration; Other Names: ACT-179811; Drug: Placebo-matching vancomycin; Placebo of vancomycin capsules
Experimental: Cadazolid 500 mg; Subjects received 500 mg of reconstituted cadazolid suspension twice daily and one placebo-matching vancomycin capsule four times daily for 10 days	Drug: Cadazolid; Cadazolid, provided as powder (250 mg, 500 mg or 1000 mg) to be reconstituted as a suspension prior to oral administration; Other Names: ACT-179811; Drug: Placebo-matching vancomycin; Placebo of vancomycin capsules
Experimental: Cadazolid 1000 mg; Subjects received 1000 mg of reconstituted cadazolid suspension twice daily and one placebo-matching vancomycin capsule four times daily for 10 days	Drug: Cadazolid; Cadazolid, provided as powder (250 mg, 500 mg or 1000 mg) to be reconstituted as a suspension prior to oral administration; Other Names: ACT-179811; Drug: Placebo-matching vancomycin; Placebo of vancomycin capsules
Active Comparator: Vancomycin 125 mg; Subjects received one vancomycin capsule (125 mg) four times daily and reconstituted placebo-matching cadazolid suspension twice daily for 10 days	Drug: Vancomycin; Vancomycin, provided as capsules (125 mg) for oral administration; Other Names: Vancomycin hydrochloride; Drug: Placebo-matching cadazolid; Placebo of cadazolid powder for oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure rate at test-of-cure	Percentages of subjects with clinical cure are calculated, with clinical cure being defined as resolution of diarrhea with no further Clostridium Difficile-associated diarrhea (CDAD) treatment required at test-of-cure (TOC) visit. Resolution of diarrhea was defined as the occurrence of ≤ 2 semi-formed or formed stools during 24 h for at least 2 consecutive 24 h periods.	Day 13 or 24-72 hours after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate	Percentages of subjects with recurrence are calculated, with recurrence being defined as the occurrence of diarrhea (> 3 liquid or unformed stools within 24 h associated with positive C. difficile toxin A/B assay) within 4 weeks after EOT in subjects clinically cured (at test-of-cure).	Between Day 13 and Day 41 (within 4 weeks after end of treatment)
Sustained cure rate	Percentages of subjects with sustained cure are calculated, with sustained cure being defined as clinical cure without CDAD recurrence up to the end of study	Between Day 13 and day 41 (within 4 weeks after end of treatment)
Time to resolution of diarrhea	Time to resolution of diarrhea was defined as the time (h) from the first intake of study treatment to the time (occurrence) of the first stool meeting the criteria for resolution of diarrhea up to test-of-cure.	From Day 1 up to Day 13 (or 24-72 hours after end of treatment)
Incidence of treatment-emergent adverse events	Percentage of subjects with any adverse events in each group from first study treatment intake up to 3 days after last study drug intake	From Day 1 to Day 14
Adverse events leading to premature discontinuation of study treatment	Number of patients in each group who discontinued the study treatment due to an adverse event	Up to Day 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified clinical cure rate	Percentage of subjects with modified clinical cure (mCC) is reported, with mCC defined as the occurrence of ≤ 3 liquid or unformed stools and any number of semi-formed or formed stools per day for at least two consecutive days, and thereafter maintained up to TOC visit. In addition, no concomitant medication active against CDAD received from the start of study treatment up to TOC	Day 13 or 24-72 hours after end of treatment

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Pascal Charef, DVM, Actelion

Publications and helpful links

General Publications

• Louie T, Nord CE, Talbot GH, Wilcox M, Gerding DN, Buitrago M, Kracker H, Charef P, Cornely OA. 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. doi: 10.1128/AAC.00504-15. Epub 2015 Jul 27.
• Gerding DN, Hecht DW, Louie T, Nord CE, Talbot GH, Cornely OA, Buitrago M, Best E, Sambol S, Osmolski JR, Kracker H, Locher HH, Charef P, Wilcox M. Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection. J Antimicrob Chemother. 2016 Jan;71(1):213-9. doi: 10.1093/jac/dkv300. Epub 2015 Oct 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2011
• Primary Completion (Actual): October 16, 2012
• Study Completion (Actual): November 12, 2012

Study Registration Dates

• First Submitted: October 8, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: CDI; Clostridium difficile infection; CDAD; CDIFF
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Vancomycin; Oxazolidinones
• Other Study ID Numbers: AC-061A201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No