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Trial record 78 of 528 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: NCT01987895
Recruitment Status : Completed
First Posted : November 20, 2013
Results First Posted : May 4, 2018
Last Update Posted : May 4, 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 632
Recruitment Details 904 patients at 70 sites in 12 countries were screened, among whom 632 were enrolled in the IMPACT 1 trial at 64 sites located in North & South America, Europe and Australia.
Pre-assignment Details  
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 day 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 day of cadazolid + 30-day follow up)
Period Title: Overall Study
Started 306 326
Completed [1] 276 296
Not Completed 30 30
Reason Not Completed
Withdrawal by Subject             12             7
Physician Decision             8             10
Death             7             7
Lost to Follow-up             3             5
randomized before giving IC             0             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 302 318 620
Hide Baseline Analysis Population Description
The baseline characteristics were defined using the modified intent-to-treat analysis set (mITT) including all randomized subjects who have received at least one dose of the study drug and had a confirmed diagnosis of CDAD
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 302 participants 318 participants 620 participants
18-64 years
180
  59.6%
203
  63.8%
383
  61.8%
65-74 years
73
  24.2%
70
  22.0%
143
  23.1%
75 years and older
49
  16.2%
45
  14.2%
94
  15.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 302 participants 318 participants 620 participants
Female
183
  60.6%
195
  61.3%
378
  61.0%
Male
119
  39.4%
123
  38.7%
242
  39.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 302 participants 318 participants 620 participants
Black or African American
3
   1.0%
9
   2.8%
12
   1.9%
Asian
2
   0.7%
3
   0.9%
5
   0.8%
Native Hawaiian or Other Pacific Islander
1
   0.3%
0
   0.0%
1
   0.2%
White
288
  95.4%
299
  94.0%
587
  94.7%
Other
2
   0.7%
4
   1.3%
6
   1.0%
Missing
6
   2.0%
3
   0.9%
9
   1.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 302 participants 318 participants 620 participants
United States
101
  33.4%
108
  34.0%
209
  33.7%
Canada
83
  27.5%
88
  27.7%
171
  27.6%
Europe
111
  36.8%
117
  36.8%
228
  36.8%
Other
7
   2.3%
5
   1.6%
12
   1.9%
CDAD episode type strata   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 302 participants 318 participants 620 participants
First occurrence
238
  78.8%
253
  79.6%
491
  79.2%
First recurrence
64
  21.2%
65
  20.4%
129
  20.8%
[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 302 participants 318 participants 620 participants
Hypervirulent strains
58
  19.2%
82
  25.8%
140
  22.6%
Non-hypervirulent strains
226
  74.8%
215
  67.6%
441
  71.1%
Unable to determine
18
   6.0%
21
   6.6%
39
   6.3%
[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 302 participants 318 participants 620 participants
Mild-Moderate
227
  75.2%
243
  76.4%
470
  75.8%
Severe
59
  19.5%
51
  16.0%
110
  17.7%
Unable to determine
16
   5.3%
24
   7.5%
40
   6.5%
[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 (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.

Time Frame Up to Day 12 on average (end-of-treatment + 2 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD.
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 302 318
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
83.8
(79.2 to 87.5)
85.2
(80.9 to 88.7)
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 -1.4
Confidence Interval (2-Sided) 95%
-7.2 to 4.3
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 -2.4
Confidence Interval (2-Sided) 95%
-8.1 to 3.2
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
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD and 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 282 288
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
87.6
(83.2 to 90.9)
91.7
(87.9 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 -4.1
Confidence Interval (2-Sided) 95%
-9.2 to 1.0
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
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD.
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 302 318
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
65.6
(60.0 to 70.7)
62.3
(56.8 to 67.4)
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 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 3.3
Confidence Interval (2-Sided) 95%
-4.3 to 10.8
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
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
The analyses were performed on the modified intention-to-treat population: all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD
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 302 318
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: KM estimate (%)
Day 1
46.7
(41.2 to 52.5)
45.9
(40.6 to 51.6)
Day 2
62.6
(57.2 to 68.0)
60.7
(55.4 to 66.1)
Day 3
69.9
(64.6 to 74.9)
71.1
(66.0 to 76.0)
Day 4
72.8
(67.7 to 77.7)
77.7
(73.0 to 82.1)
Day 5
77.8
(73.0 to 82.3)
80.2
(75.6 to 84.4)
Day 6
81.1
(76.5 to 85.3)
81.8
(77.3 to 85.8)
Day 7
82.5
(78.0 to 86.5)
84.6
(80.4 to 88.3)
Day 8
83.4
(79.0 to 87.4)
85.2
(81.1 to 88.9)
Day 9
83.8
(79.4 to 87.7)
85.2
(81.1 to 88.9)
Day 10
83.8
(79.4 to 87.7)
85.2
(81.1 to 88.9)
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 0.6016
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 0.96
Confidence Interval (2-Sided) 95%
0.80 to 1.14
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. The least squares means (LSM) are computed on the scores.
Time Frame Day 1 (baseline) and Day 3
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 246 260
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
Diarrhea symptoms
-1.233
(-1.37 to -1.09)
-1.235
(-1.37 to -1.10)
Abdominal symptoms
-0.623
(-0.74 to -0.51)
-0.710
(-0.82 to -0.60)
Other symptoms
-0.639
(-0.74 to -0.54)
-0.689
(-0.79 to -0.59)
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 0.9814
Comments Two-sided 5% alpha level was used
Method ANOVA
Comments ANOVA 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 0.002
Confidence Interval (2-Sided) 95%
-0.20 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 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 0.2879
Comments Two-sided 5% alpha level was used
Method ANOVA
Comments ANOVA 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 0.087
Confidence Interval (2-Sided) 95%
-0.07 to 0.25
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 systemic / other symptoms domain scores
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4880
Comments Two-sided 5% alpha level was used
Method ANOVA
Comments ANOVA 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 0.050
Confidence Interval (2-Sided) 95%
-0.09 to 0.19
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
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD.
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 302 318
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
89.7
(85.8 to 92.7)
91.5
(87.9 to 94.1)
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 -1.8
Confidence Interval (2-Sided) 95%
-6.5 to 2.9
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
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD and 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 282 288
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
92.2
(88.5 to 94.8)
94.1
(90.8 to 96.3)
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 -1.9
Confidence Interval (2-Sided) 95%
-6.2 to 2.3
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
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD.
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 302 318
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
73.8
(68.6 to 78.5)
70.1
(64.9 to 74.9)
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 3.7
Confidence Interval (2-Sided) 95%
-3.4 to 10.7
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
All subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD and 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 282 288
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
68.8
(63.2 to 73.9)
67.7
(62.1 to 72.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cadazolid, Vancomycin
Comments [Not Specified]
Type of Statistical Test Other
Comments Sensitivity analysis
Method of Estimation Estimation Parameter Difference between 2 proportions
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-6.5 to 8.7
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 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 253 271
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15
(11.1 to 19.9)
21.4
(16.9 to 26.7)
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 [Not Specified]
 
Arm/Group Title Cadazolid Vancomycin
Hide Arm/Group Description 304 subjects received at least one dose of cadazolid and were included in the safety analysis. The median duration of treatment with cadazolid was 10 days. 322 subjects received at least one dose of vancomycin and were included in the safety analysis. The median duration of treatment with vancomycin was 10 days.
All-Cause Mortality
Cadazolid Vancomycin
Affected / at Risk (%) Affected / at Risk (%)
Total   7/304 (2.30%)      7/322 (2.17%)    
Show Serious Adverse Events Hide Serious Adverse Events
Cadazolid Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/304 (6.25%)      26/322 (8.07%)    
Blood and lymphatic system disorders     
Disseminated intravascular coagulation  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Thrombocytopenia  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Cardiac disorders     
Acute myocardial infarction  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Atrioventricular block second degree  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Cardiac failure  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Cardiac failure chronic  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Cardiac failure congestive  1  1/304 (0.33%)  1 1/322 (0.31%)  1
Cardio-respiratory arrest  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Myocardial infarction  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Gastrointestinal disorders     
Ascites  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Gastrointestinal haemorrhage  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Megacolon  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Pancreatitis  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Rectal stenosis  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Small intestinal obstruction  1  0/304 (0.00%)  0 1/322 (0.31%)  1
General disorders     
Oedema peripheral  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Hepatobiliary disorders     
Cholangitis  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Cholangitis acute  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Hypertransaminasaemia  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Infections and infestations     
Abdominal abscess  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Arthritis bacterial  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Cellulitis  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Cellulitis of male external genital organ  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Clostridium difficile infection  1  2/304 (0.66%)  2 8/322 (2.48%)  8
Endocarditis  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Perineal abscess  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Peritonitis bacterial  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Pneumonia  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Pseudomembranous colitis  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Sepsis  1  2/304 (0.66%)  2 2/322 (0.62%)  2
Septic shock  1  1/304 (0.33%)  1 1/322 (0.31%)  1
Sinusitis  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Urinary tract infection  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Urinary tract infection pseudomonal  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Injury, poisoning and procedural complications     
Anaemia postoperative  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Biliary anastomosis complication  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Diabetic ketoacidosis  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Hyperglycaemia  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic cancer  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Metastases to central nervous system  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Metastatic carcinoma of the bladder  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Chronic kidney disease  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Renal failure  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute chest syndrome  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Acute pulmonary oedema  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Pulmonary embolism  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Pulmonary oedema  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Respiratory failure  1  1/304 (0.33%)  1 1/322 (0.31%)  1
Skin and subcutaneous tissue disorders     
Skin ulcer  1  1/304 (0.33%)  1 0/322 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  2/304 (0.66%)  2 0/322 (0.00%)  0
Hypotension  1  0/304 (0.00%)  0 1/322 (0.31%)  1
Peripheral vascular disorder  1  0/304 (0.00%)  0 1/322 (0.31%)  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   33/304 (10.86%)      49/322 (15.22%)    
Gastrointestinal disorders     
Abdominal pain  1  14/304 (4.61%)  16 22/322 (6.83%)  24
Nausea  1  12/304 (3.95%)  13 24/322 (7.45%)  27
Nervous system disorders     
Headache  1  14/304 (4.61%)  17 25/322 (7.76%)  28
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
Layout table for Results Point of Contact information
Name/Title: Clinical Trial disclosure Desk
Organization: Actelion Pharmaceuticals Ltd
Phone: 0041615656565
EMail: clinical-trials-disclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01987895     History of Changes
Other Study ID Numbers: AC-061A301
First Submitted: November 7, 2013
First Posted: November 20, 2013
Results First Submitted: February 23, 2018
Results First Posted: May 4, 2018
Last Update Posted: May 4, 2018