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: NCT01983683
• Other study ID #: AC-061A302
• Status: Completed
• Phase: Phase 3
• Start date: December 12, 2013
• Est. completion date: May 2, 2017

Study information

• Verified date: April 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: 631
• Est. completion date: May 2, 2017
• Est. primary completion date: March 9, 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
Argentina	Investigator Site	Cordoba
Argentina	Investigator Site	La Plata
Belgium	Investigator Site	Brussels
Belgium	Investigator Site	Bruxelles
Belgium	Investigator Site	Gent
Belgium	Investigator Site	Leuven
Brazil	Investigator Site	Belo Horizonte
Brazil	Investigator Site	Porto Alegre
Canada	Investigator Site	Chicoutimi	Quebec
Canada	Investigator Site	London	Ontario
Canada	Investigator Site	Moncton	New Brunswick
Canada	Investigator Site	Surrey	British Columbia
Canada	Investigator Site	Trois-Rivieres	Quebec
Canada	Investigator Site	Vancouver	British Columbia
Chile	Investigator Site	Santiago
Chile	Investigator Site	Santiago
Croatia	Investigator Site 2788	Pozega
Croatia	Investigator Site 2780	Zagreb
Croatia	Investigator Site 2781	Zagreb
Croatia	Investigator Site 2784	Zagreb
Croatia	Investigator Site 2785	Zagreb
Croatia	Investigator Site 2786	Zagreb
Czechia	Investigator Site	Brno
Czechia	Investigator Site	Opava
Czechia	Investigator Site	Ostrava
Czechia	Investigator Site	Praha
Czechia	Investigator Site	Praha 4
Greece	Investigator Site	Athens
Greece	Investigator Site	Athens
Greece	Investigator Site	Athens
Greece	Investigator Site	Piraeus
Hungary	Investigator Site	Budapest
Hungary	Investigator Site	Debrecen
Hungary	Investigator Site	Szekszard
Israel	Investigator Site	Hadera
Israel	Investigator Site	Haifa
Israel	Investigator Site	Holon
Israel	Investigator Site	Jerusalem
Israel	Investigator Site	Kfar Saba
Israel	Investigator Site	Petach Tikva
Israel	Investigator Site	Ramat-Gan
Korea, Republic of	Investigator Site	Seoul
Korea, Republic of	Investigator Site	Seoul
Korea, Republic of	Investigator Site	Seoul
Romania	Investigator Site	Bucharest
Romania	Investigator Site	Bucharest
Romania	Investigator Site	Cluj-Napoca
Romania	Investigator Site	Galati
Romania	Investigator Site	Iasi
Slovakia	Investigator Site	Bratislava
Slovakia	Investigator Site	Nitra
United States	Investigator Site	Annandale	Virginia
United States	Investigator Site	Annapolis	Maryland
United States	Investigator Site	Birmingham	Alabama
United States	Investigator Site	Bowling Green	Kentucky
United States	Investigator Site	Brooklyn	New York
United States	Investigator Site	Buffalo	New York
United States	Investigator Site	Butte	Montana
United States	Investigator Site	Chicago	Illinois
United States	Investigator Site	Cincinnati	Ohio
United States	Investigator Site	Cypress	Texas
United States	Investigator Site	Dallas	Texas
United States	Investigator Site	Detroit	Michigan
United States	Investigator Site	Detroit	Michigan
United States	Investigator Site	Fayetteville	North Carolina
United States	Investigator Site	Framingham	Massachusetts
United States	Investigator Site	Houston	Texas
United States	Investigator Site	Jackson	Mississippi
United States	Investigator Site	Jacksonville	North Carolina
United States	Investigator Site	Kinston	North Carolina
United States	Investigator Site	Laguna Hills	California
United States	Investigator Site	Lewiston	Maine
United States	Investigator Site	Marietta	Georgia
United States	Investigator Site	Marshfield	Wisconsin
United States	Investigator Site	Mentor	Ohio
United States	Investigator Site	Mission Hills	California
United States	Investigator Site	Monroeville	Pennsylvania
United States	Investigator Site	New Orleans	Louisiana
United States	Investigator Site	Orlando	Florida
United States	Investigator Site	Pensacola	Florida
United States	Investigator Site	Philadelphia	Pennsylvania
United States	Investigator Site	Port Saint Lucie	Florida
United States	Investigator Site	Rialto	California
United States	Investigator Site	Saint Paul	Minnesota
United States	Investigator Site	Shreveport	Louisiana
United States	Investigator Site	Stuart	Florida
United States	Investigator Site	Toledo	Ohio
United States	Investigator Site	Wenatchee	Washington
United States	Investigator Site	West Jordan	Utah
United States	Investigator Site	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  Croatia,  Czechia,  Greece,  Hungary,  Israel,  Korea, Republic of,  Romania,  Slovakia, 

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 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)
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 (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
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.	Baseline to End of Treatment (10 days after starting study drug) + 2 days