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Trial record 79 of 530 for:    VANCOMYCIN

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01983683
Recruitment Status : Completed
First Posted : November 14, 2013
Results First Posted : April 13, 2018
Last Update Posted : May 24, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Clostridium Difficile Infection
Interventions Drug: Cadazolid
Drug: Vancomycin
Drug: Cadazolid-matching placebo
Drug: Vancomycin-matching placebo
Enrollment 631
Recruitment Details 1128 patients at 105 sites in 15 countries were screened, among whom 631 were randomized at 96 sites in 14 countries worldwide.
Pre-assignment Details Among the 631 subjects randomized, 22 were excluded from all the analyses due to potential data integrity issues resulting in 609 total participants considered for the analyses. From the 22 excluded patients no serious adverse events (AEs) or study drug discontinuation information were reported. All reported AEs were mild or moderate in intensity.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description Subjects with Clostridium difficile-associated diarrhea (CDAD) received oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times a day (qid) for 10 days. Subjects were followed up for 30 days after the last dose of cadazolid. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up) Subjects with CDAD received oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days. Subjects were followed up for 30 day after the last dose of vancomycin. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up)
Period Title: Overall Study
Started 298 311
Completed [1] 260 260
Not Completed 38 51
Reason Not Completed
Withdrawal by Subject             14             18
Death             11             15
Physician Decision             8             9
Lost to Follow-up             4             8
Sponsor Decision             1             1
[1]
Include subjects who completed the main study + subjects who completed the re-treatment extension
Arm/Group Title Cadazolid Vancomycin Total
Hide Arm/Group Description Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days Total of all reporting groups
Overall Number of Baseline Participants 290 301 591
Hide Baseline Analysis Population Description
The modified-intent-to-treat population (mITT) was used: all subjects who have received at least one dose of the study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
18-64 years
139
  47.9%
152
  50.5%
291
  49.2%
65-74 years
64
  22.1%
60
  19.9%
124
  21.0%
75 years and older
87
  30.0%
89
  29.6%
176
  29.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
Female
187
  64.5%
183
  60.8%
370
  62.6%
Male
103
  35.5%
118
  39.2%
221
  37.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
Black or African American
12
   4.1%
15
   5.0%
27
   4.6%
American Indian or Alaska Native
0
   0.0%
1
   0.3%
1
   0.2%
Asian
7
   2.4%
5
   1.7%
12
   2.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.3%
1
   0.2%
Whtie
266
  91.7%
271
  90.0%
537
  90.9%
Other
5
   1.7%
8
   2.7%
13
   2.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
United States
102
  35.2%
107
  35.5%
209
  35.4%
Canada
15
   5.2%
16
   5.3%
31
   5.2%
Europe
121
  41.7%
124
  41.2%
245
  41.5%
Other
52
  17.9%
54
  17.9%
106
  17.9%
CDAD episode type strata   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
First occurrence
235
  81.0%
246
  81.7%
481
  81.4%
First recurrence
55
  19.0%
55
  18.3%
110
  18.6%
[1]
Measure Description: CDAD episode type strata was defined as baseline stratification factor ‘First occurrence’ or ‘First recurrence’ of CDAD as recorded in the Interactive voice recognition system (IVRS) at the time of subject randomization. Number of subjects with first recurrence or first occurrence at randomization was assessed for each treatment group.
Initial strain of Clostridium difficile   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
Hypervirulent strains
75
  25.9%
88
  29.2%
163
  27.6%
Non-hypervirulent strains
181
  62.4%
183
  60.8%
364
  61.6%
Unable to determine
34
  11.7%
30
  10.0%
64
  10.8%
[1]
Measure Description: The strain of C. difficile at baseline was identified in the last stool sample collected up to treatment start date and with available C. difficile culture. Identification was done by polymerase chain reaction (PCR). The strains were categorized as hypervirulent strains (PCR ribotype 027, 078 or 244) or non-hypervirulent (other PCR ribotypes). The number of subjects with hypervirulent, non-hypervirulent strains at baseline was assessed for each treatment group. If PCR ribotype at baseline was not available, the subjects were classified as "unable to determine"
CDAD severity at baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 301 participants 591 participants
Mild-Moderate
216
  74.5%
227
  75.4%
443
  75.0%
Severe
54
  18.6%
57
  18.9%
111
  18.8%
Unable to determine
20
   6.9%
17
   5.6%
37
   6.3%
[1]
Measure Description: CDAD at baseline was considered as severe if the following criteria were met: maximum body temperature > 38.5 C, white blood cell counts > 15.0 x 10*9/L and rise in baseline serum creatinine > 50% compared to the level before CDAD diagnosis. Otherwise, it was considered as mild-moderate. The number of subjects with severe and mild-moderate CDAD at baseline was assessed for each treatment group. If any of the measurements required for derivation of severity was missing, the subjects were classified as "unable to determine"
1.Primary Outcome
Title Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population
Hide Description 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.
Time Frame Up to Day 12 on average (end-of-treatment + 2 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 290 301
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
81
(76.1 to 85.1)
85.7
(81.3 to 89.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority of CCR for cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above –10%
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value -4.7
Confidence Interval (2-Sided) 95%
-10.7 to 1.3
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Sensitivity analysis with imputation for a single day with missing UBM data between one day before end-of-treatment (EOT) and 2 days after EOT
Type of Statistical Test Non-Inferiority
Comments Non-inferiority of CCR for cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above –10%
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-9.6 to 2.3
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
2.Primary Outcome
Title Clinical Cure Rate (CCR) in the Per-protocol Population
Hide Description 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.
Time Frame Up to Day 12 on average (end-of-treatment + 2 days)
Hide Outcome Measure Data
Hide Analysis Population Description
per-protocol population: all subjects from the mITT population without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 247 259
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
86.6
(81.8 to 90.3)
91.5
(87.5 to 94.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Non-inferiority of CCR for cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above –10%
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value -4.9
Confidence Interval (2-Sided) 95%
-10.4 to 0.6
Estimation Comments CI for the difference between two proportions are estimated using the Wilson' score method
3.Secondary Outcome
Title Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population
Hide Description 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).
Time Frame Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 290 301
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
63.4
(57.8 to 68.8)
61.8
(56.2 to 67.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Superiority of cadazolid versus vancomycin is demonstrated if the lower limit of the 95% confidence interval (CI) is above zero
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
-6.1 to 9.4
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
4.Secondary Outcome
Title Kaplan-Meier Estimates for Resolution of Diarrhea (ROD)
Hide Description

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.

Time Frame Up to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 290 301
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: KM estimate (% subjects with ROD)
Day 1
51.0
(45.4 to 56.9)
45.8
(40.4 to 51.6)
Day 2
64.5
(59.0 to 70.0)
59.8
(54.3 to 65.4)
Day 3
69.7
(64.3 to 74.8)
67.8
(62.5 to 73.0)
Day 4
73.8
(68.6 to 78.7)
72.8
(67.6 to 77.7)
Day 5
77.9
(73.0 to 82.5)
78.4
(73.6 to 82.9)
Day 6
77.9
(73.0 to 82.5)
81.4
(76.8 to 85.6)
Day 7
79.7
(74.8 to 84.1)
83.7
(79.3 to 87.6)
Day 8
81.0
(76.3 to 85.3)
85.7
(81.5 to 89.4)
Day 9
81.0
(76.3 to 85.3)
85.7
(81.5 to 89.4)
Day 10
81.0
(76.3 to 85.3)
85.7
(81.5 to 89.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7794
Comments two-sided p-value (alpha 5%) based on log-rank test stratified by first occurrence / first recurrence and geographical region.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.86 to 1.24
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores
Hide Description 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.
Time Frame Baseline to End of Treatment (10 days after starting study drug) + 2 days
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects from the modified intent-to-treat population, excluding those who participated in the validation sub-study. No imputation of missing scores is performed prior to deriving response status. Subjects with missing values at baseline or at Day 3 are considered to be non-responders.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 232 245
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Scores on a scale
Diarrhea symptoms
-1.242
(-1.4 to -1.09)
-1.199
(-1.35 to -1.05)
Abdominal symptoms
-0.669
(-0.79 to -0.54)
-0.693
(-0.82 to -0.57)
Other symptoms
-0.67
(-0.77 to -0.56)
-0.731
(-0.83 to -0.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Comparison of the diarrhea domain scores
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6871
Comments Two-sided 5% alpha level was used
Method ANOVA
Comments ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12.
Method of Estimation Estimation Parameter Least Square Mean difference
Estimated Value -0.044
Confidence Interval (2-Sided) 95%
-0.26 to 0.17
Estimation Comments The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Comparison of the abdominal symptoms domain scores
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7833
Comments Two-sided 5% alpha level was used
Method ANOVA
Comments ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12.
Method of Estimation Estimation Parameter Least Square Mean difference
Estimated Value 0.025
Confidence Interval (2-Sided) 95%
-0.15 to 0.20
Estimation Comments The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Comparison of the other symptoms domain scores
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4145
Comments Two-sided 5% alpha level was used
Method ANOVA
Comments ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12.
Method of Estimation Estimation Parameter Least Square Mean difference
Estimated Value 0.061
Confidence Interval (2-Sided) 95%
-0.09 to 0.21
Estimation Comments The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements
6.Other Pre-specified Outcome
Title Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population
Hide Description 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.
Time Frame Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population: all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 290 301
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
87.2
(82.9 to 90.6)
88.4
(84.3 to 91.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Exploratory analysis
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-6.5 to 4.2
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
7.Other Pre-specified Outcome
Title Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population
Hide Description 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.
Time Frame Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population: all subjects from the mITT analysis set without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 247 259
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
91.1
(86.9 to 94.0)
92.7
(88.8 to 95.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Exploratory analysis
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-6.5 to 3.3
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
8.Other Pre-specified Outcome
Title Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5
Hide Description 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).
Time Frame Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 290 301
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
69.3
(63.8 to 74.3)
60.5
(54.8 to 65.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments Exploratory analysis
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value 8.8
Confidence Interval (2-Sided) 95%
1.1 to 16.4
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
9.Other Pre-specified Outcome
Title Sustained Cure Rate (SCR) in the Per-protocol Population
Hide Description 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.
Time Frame Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population: all subjects from the mITT population without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 247 259
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
67.6
(61.5 to 73.1)
64.9
(58.9 to 70.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Sensitivity analysis
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
-5.5 to 10.9
Estimation Comments CI for the difference between two proportions are estimated using the Wilson's score method
10.Other Pre-specified Outcome
Title Recurrence Rate
Hide Description 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.
Time Frame Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects from the modified intent-to-treat analysis set (mITT) with clinical cure
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description:
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days
Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days
Overall Number of Participants Analyzed 235 258
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
15.7
(11.6 to 20.9)
17.8
(13.6 to 23.0)
Time Frame Serious and frequent adverse events are reported from study treatment initiation up to Day 17 on average (i.e., 7 days after end-of-treatment or study withdrawal) and all-cause mortality up to Day 40 on average (i.e. 28 to 32 days after end-of-treatment or study withdrawal)
Adverse Event Reporting Description 294 subjects who received at least one dose of cadazolid (cadazolid arm) and 307 subjects who received at least one dose of vancomycin (vancomycin arm) were included in the safety analysis. The median duration of treatment was 10 days in both arms.
 
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description oral cadazolid 250 mg twice daily (bid) for 10 days oral vancomycin 125 mg 4 times per day (qid) for 10 days
All-Cause Mortality
Cadazolid Vancomycin
Affected / at Risk (%) Affected / at Risk (%)
Total   11/294 (3.74%)      15/307 (4.89%)    
Show Serious Adverse Events Hide Serious Adverse Events
Cadazolid Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/294 (11.90%)      46/307 (14.98%)    
Blood and lymphatic system disorders     
Anaemia  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Bone marrow failure  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Leukopenia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Neutropenia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Thrombocytopenia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Cardiac disorders     
Atrial fibrillation  1  0/294 (0.00%)  0 1/307 (0.33%)  2
Bradycardia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Cardiac arrest  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Cardiac failure acute  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Cardiac failure chronic  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Cardiac failure congestive  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Cardiopulmonary failure  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Supraventricular tachycardia  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Ventricular tachycardia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Congenital, familial and genetic disorders     
Porphyria acute  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Abdominal pain  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Enterocolitis  1  2/294 (0.68%)  2 0/307 (0.00%)  0
Enterocolitis haemorrhagic  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Ileus  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Melaena  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Small intestinal obstruction  1  0/294 (0.00%)  0 1/307 (0.33%)  1
General disorders     
Chest pain  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Multiple organ dysfunction syndrome  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Pyrexia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Hepatobiliary disorders     
Cholangitis  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Cholecystitis acute  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Liver injury  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Immune system disorders     
Transplant rejection  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Infections and infestations     
Bronchitis fungal  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Clostridium difficile colitis  1  2/294 (0.68%)  2 2/307 (0.65%)  2
Clostridium difficile infection  1  5/294 (1.70%)  5 11/307 (3.58%)  11
Device related infection  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Enterobacter sepsis  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Enterococcal bacteraemia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Escherichia bacteraemia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Escherichia urinary tract infection  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Gastroenteritis  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Haematoma infection  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Herpes simplex hepatitis  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Infectious pleural effusion  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Lung infection  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Meningitis  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Peritonitis  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Pneumonia  1  1/294 (0.34%)  1 4/307 (1.30%)  4
Pneumonia klebsiella  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Pseudomembranous colitis  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Pulmonary sepsis  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Sepsis  1  4/294 (1.36%)  4 1/307 (0.33%)  1
Septic shock  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Transplant abscess  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Urinary tract infection  1  0/294 (0.00%)  0 4/307 (1.30%)  4
Urinary tract infection bacterial  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Injury, poisoning and procedural complications     
Contrast media reaction  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Joint dislocation  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Post procedural haematoma  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Investigations     
Blood creatine phosphokinase increased  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Escherichia test positive  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Hyponatraemia  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Rectal cancer  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Renal cancer metastatic  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Squamous cell carcinoma  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Nervous system disorders     
Cerebral infarction  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Hepatic encephalopathy  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Ischaemic stroke  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Psychiatric disorders     
Confusional state  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Renal and urinary disorders     
Acute kidney injury  1  2/294 (0.68%)  2 1/307 (0.33%)  1
Chronic kidney disease  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Renal failure  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Renal impairment  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Renal tubular necrosis  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  0/294 (0.00%)  0 2/307 (0.65%)  2
Acute respiratory failure  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Atelectasis  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Pleural effusion  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Pneumonia aspiration  1  0/294 (0.00%)  0 1/307 (0.33%)  1
Respiratory distress  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Respiratory failure  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Vascular disorders     
Hypovolaemic shock  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Peripheral embolism  1  1/294 (0.34%)  1 0/307 (0.00%)  0
Peripheral ischaemia  1  1/294 (0.34%)  1 1/307 (0.33%)  1
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cadazolid Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   47/294 (15.99%)      51/307 (16.61%)    
Gastrointestinal disorders     
Nausea  1  16/294 (5.44%)  19 11/307 (3.58%)  13
General disorders     
Pyrexia  1  15/294 (5.10%)  20 11/307 (3.58%)  12
Infections and infestations     
Clostridium difficile infection  1  10/294 (3.40%)  11 17/307 (5.54%)  17
Nervous system disorders     
Headache  1  13/294 (4.42%)  15 18/307 (5.86%)  21
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
Results Point of Contact
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Name/Title: clinical trial disclosure desk
Organization: Actelion Pharmaceuticals Ltd
Phone: 0041615656565
EMail: clinical-trials-disclosure@its.jnj.com
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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01983683     History of Changes
Other Study ID Numbers: AC-061A302
First Submitted: November 7, 2013
First Posted: November 14, 2013
Results First Submitted: March 9, 2018
Results First Posted: April 13, 2018
Last Update Posted: May 24, 2018