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Trial record 5 of 23 for:    CDAD AND VANCOMYCIN

Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile - Associated Diarrhea

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ClinicalTrials.gov Identifier: NCT01987895
Recruitment Status : Completed
First Posted : November 20, 2013
Results First Posted : May 4, 2018
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

Brief Summary:
This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).

Condition or disease Intervention/treatment Phase
Clostridium Difficile Infection Drug: Cadazolid Drug: Vancomycin Drug: Cadazolid-matching placebo Drug: Vancomycin-matching placebo Phase 3

Detailed Description:
Subjects selected to participate in the study are treated either with cadazolid or vancomycin for 10 days. At the end of treatment, clinical cure is assessed; subjects are then followed-up to assess any disease recurrence.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 632 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : March 27, 2014
Actual Primary Completion Date : February 26, 2017
Actual Study Completion Date : March 24, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea

Arm Intervention/treatment
Experimental: Cadazolid
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Drug: Cadazolid
Cadazolid 250 mg as oral suspension twice daily.
Other Name: ACT-179811

Drug: Vancomycin-matching placebo
Placebo capsules matching vancomycin and administered orally 4 times per day

Active Comparator: Vancomycin
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Drug: Vancomycin
Vancomycin 125 mg as oral capsules 4 times daily.
Other Name: Vancocin

Drug: Cadazolid-matching placebo
Placebo matching cadazolid and administered orally twice daily




Primary Outcome Measures :
  1. Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population [ Time Frame: Up to Day 12 on average (end-of-treatment + 2 days) ]

    Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT.

    CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.


  2. Clinical Cure Rate (CCR) in the Per-protocol Population [ Time Frame: Up to Day 12 on average (end-of-treatment + 2 days) ]
    Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.


Secondary Outcome Measures :
  1. Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population [ Time Frame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) ]
    Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The main analysis is performed on the modified intent-to-treat set (mITT).

  2. Kaplan-Meier Estimates for Resolution of Diarrhea [ Time Frame: Up to Day 10 ]

    Resolution of Diarrhea (ROD) is defined as no more than 3 unformed bowel movements per day for at least two consecutive days for subjects on study treatment.

    The Kaplan-Meier estimates (KM estimates) for having an event (ROD) are reported for each time point.


  3. Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores [ Time Frame: Day 1 (baseline) and Day 3 ]
    CDI-DaySyms PRO is a questionnaire assessing 10 symptoms relevant to subjects with CDAD and grouped into 3 domains: Diarrhea symptoms, Abdominal symptoms and Systemic/Other. The subjects rate the severity of each item as None, Mild, Moderate, Severe or Very severe, converted to numeric scores from 0 to 4, respectively. The daily domain score is calculated as the mean of the non-missing responses for that domain on that day. A negative value for change from baseline corresponds to an improvement in domain score. The three domains are evaluated in a hierarchical manner, starting with Diarrhea Symptoms, then Abdominal Symptoms, and finally Systemic/Other Symptoms. The least squares means (LSM) are computed on the scores.


Other Outcome Measures:
  1. Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population [ Time Frame: Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) ]
    ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.

  2. Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population [ Time Frame: Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) ]
    ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. ICR rate (%) is the percentage of subjects with ICR assessed as cured. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.

  3. Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5 [ Time Frame: Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days) ]

    ISR rate (%) is the percentage of subjects assessed as Sustained Cure at Visit 5, according to the investigator's own judgement. Sustained Cure is defined for each subject having Clinical Cure and no recurrence. Subjects with missing assessment are considered as having 'Not Sustained Cure' for the analysis.

    ISR rate is used as a supportive measure of the secondary efficacy endpoint (SCR). Analyses are performed on the modified intent-to-treat set (mITT).


  4. Sustained Cure Rate (SCR) in the Per-protocol Population [ Time Frame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) ]
    Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The analyses performed on the modified intent-to- treat set (mITT) are repeated on the per-protocol set (PPS) for sensitivity.

  5. Recurrence Rate [ Time Frame: Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days) ]
    Recurrence is defined as the occurrence of a new episode of diarrhea (> 3 unformed bowel movements on any day between end-of-treatment + 3 days and end-of-treatment + 30 days ) Recurrence rates is the percentage of subjects assessed as having a recurrence out of subjects with Clinical Cure.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization.

Exclusion Criteria:

  • More than one previous episode of CDAD in the 3-month period prior to randomization.
  • Evidence of life-threatening or fulminant CDAD.
  • Likelihood of death within 72 hours from any cause.
  • History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea.
  • Antimicrobial treatment active against CDAD administered for > 24 hours except for metronidazole treatment failures (MTF)
  • Known hypersensitivity or contraindication to study drugs, oxazolidinones, or quinolones.
  • Unable or unwilling to comply with all protocol requirements.
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01987895


  Show 64 Study Locations
Sponsors and Collaborators
Actelion
Investigators
Study Director: Anne Claire Marrast, MD Actelion
  Study Documents (Full-Text)

Documents provided by Actelion:
Statistical Analysis Plan  [PDF] May 19, 2017
Study Protocol  [PDF] October 22, 2015


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01987895     History of Changes
Other Study ID Numbers: AC-061A301
First Posted: November 20, 2013    Key Record Dates
Results First Posted: May 4, 2018
Last Update Posted: May 4, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Actelion:
Post-antibiotic diarrhea
Clostridium difficile infection

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Vancomycin
Oxazolidinones
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action