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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Cadazolid
* Drug: Vancomycin
* Drug: Placebo-matching cadazolid
* Drug: Placebo-matching vancomycin


Participation Criteria
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Eligibility Criteria
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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

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: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDIFF, CDAD, CDI, Clostridium difficile infection