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

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

Detailed Description
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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.

Official Title
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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).

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Cadazolid
* Drug: Vancomycin
* Drug: Cadazolid-matching placebo
* Drug: Vancomycin-matching placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cadazolid<br>Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days | Drug: Cadazolid<br>* Cadazolid 250 mg as oral suspension twice daily.<br>* Other names: ACT-179811;Drug: Vancomycin-matching placebo<br>* Placebo capsules matching vancomycin and administered orally 4 times per day<br>|
| Active Comparator: Vancomycin<br>Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days | Drug: Vancomycin<br>* Vancomycin 125 mg as oral capsules 4 times daily<br>* Other names: Vancocin;Drug: Cadazolid-matching placebo<br>* Placebo matching cadazolid and administered orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population | Clinical Cure is defined as: • Resolution of Diarrhea (ROD) (≤ 3 unformed bowel movement (UBM) 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 (FMT) between first dose of study drug and 2 days after EOT (inclusive). 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. | Up to Day 12 on average (end-of-treatment + 2 days) | 
| Clinical Cure Rate (CCR) in the Per-protocol Population | 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. | Up to Day 12 on average (end-of-treatment + 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population | 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). | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) | 
| Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | 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. | Up to Day 10 | 
| Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | 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. | Baseline to End of Treatment (10 days after starting study drug) + 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium difficile infection, Post-antibiotic diarrhea