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

Clostridium Difficile Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01987895
• Other study ID #: AC-061A301
• Status: Completed
• Phase: Phase 3
• Start date: March 27, 2014
• Est. completion date: March 24, 2017

Study information

• Verified date: May 2018
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 632
• Est. completion date: March 24, 2017
• Est. primary completion date: February 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Difficile Infection
• Diarrhea

Intervention

Drug:
• Cadazolid
Cadazolid 250 mg as oral suspension twice daily.
• Vancomycin
Vancomycin 125 mg as oral capsules 4 times daily.
• Cadazolid-matching placebo
Placebo matching cadazolid and administered orally twice daily
• Vancomycin-matching placebo
Placebo capsules matching vancomycin and administered orally 4 times per day

Locations

Country	Name	City	State
Australia	Investigator Site	Geelong
Australia	Investigator Site	Southport
Brazil	Investigator Site	Porto Alegre
Brazil	Investigator Site	Salvador	Bahia
Brazil	Investigator Site	Sao Paulo
Canada	Investigator Site	Calgary
Canada	Investigator Site	Edmonton
Canada	Investigator Site	Hamilton
Canada	Investigator Site	Montreal
Canada	Investigator Site	Saint-Jerome
Canada	Investigator Site	Toronto	Ontario
France	Investigator Site	Dijon
France	Investigator Site	Grenoble
France	Investigator Site	Lille
France	Investigator Site	Orleans
France	Investigator Site	Paris
France	Investigator Site	Paris
Germany	Investigator Site	Hamburg
Germany	Investigator Site	Koln
Italy	Investigator Site	Bergamo
Italy	Investigator Site	Monza
Italy	Investigator Site	Roma
Italy	Investigator Site	Roma
Netherlands	Investigator Site	Apeldoorn
Netherlands	Investigator Site	Dordrecht
Peru	Investigator Site	Lima
Poland	Investigator Site	Lancut
Poland	Investigator Site	Lodz
Poland	Investigator Site	Myslowice
Poland	Investigator Site	Wroclaw
Romania	Investigator Site	Bucharest
Romania	Investigator Site	Craiova
Spain	Investigator Site	Barcelona
Spain	Investigator Site	Barcelona
Spain	Investigator Site	Barcelona
Spain	Investigator Site	Boadilla del Monte
Spain	Investigator Site	Lleida
Spain	Investigator Site	Madrid
Spain	Investigator Site	Majadahonda
United States	Investigator Site	Aurora	Colorado
United States	Investigator Site	Boston	Massachusetts
United States	Investigator Site	Brooklyn	New York
United States	Investigator Site	Carmel	Indiana
United States	Investigator Site	Chevy Chase	Maryland
United States	Investigator Site	Dallas	Texas
United States	Investigator Site	Dayton	Ohio
United States	Investigator Site	Decatur	Georgia
United States	Investigator Site	Houston	Texas
United States	Investigator Site	Idaho Falls	Idaho
United States	Investigator Site	Lansdowne Town Center	Virginia
United States	Investigator Site	Lima	Ohio
United States	Investigator Site	Mobile	Alabama
United States	Investigator Site	Naples	Florida
United States	Investigator Site	New York	New York
United States	Investigator Site	New York	New York
United States	Investigator Site	Oceanside	California
United States	Investigator Site	Omaha	Nebraska
United States	Investigator Site	Pittsburgh	Pennsylvania
United States	Investigator Site	Port Orange	Florida
United States	Investigator Site	Sacramento	California
United States	Investigator Site	South Weymouth	Massachusetts
United States	Investigator Site	Syracuse	New York
United States	Investigator Site	West Palm Beach	Florida
United States	Investigator Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Italy,  Netherlands,  Peru,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population	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.	Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
Other	Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population	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.	Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
Other	Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5	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).	Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days)
Other	Sustained Cure Rate (SCR) in the Per-protocol Population	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.	Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Other	Recurrence Rate	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.	Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days)
Primary	Clinical Cure Rate (CCR) in the Modified Intent-to-treat 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 modified intent-to-treat set (mITT) are reported below.	Up to Day 12 on average (end-of-treatment + 2 days)
Primary	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	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)
Secondary	Kaplan-Meier Estimates for Resolution of Diarrhea	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
Secondary	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. The least squares means (LSM) are computed on the scores.	Day 1 (baseline) and Day 3