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Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-005)

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ClinicalTrials.gov Identifier: NCT01597505
Recruitment Status : Completed
First Posted : May 14, 2012
Results First Posted : February 28, 2018
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Clostridium Difficile Infection
Interventions Drug: Surotomycin
Drug: Vancomycin
Drug: Placebo
Enrollment 606
Recruitment Details Males and females aged 18 years or older with diarrhea at risk for Clostridium Difficile Associated Diarrhea (CDAD) were enrolled in this study
Pre-assignment Details  
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description 250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days 125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Period Title: Overall Study
Started 308 [1] 298 [1]
Treated 305 [2] 286
Completed 264 265
Not Completed 44 33
Reason Not Completed
Physician Decision             5             0
Adverse Event             19             7
Lost to Follow-up             4             2
Withdrawal by Subject             10             18
Other             5             6
Missing             1             0
[1]
Randomized participants
[2]
One participant was instead randomized to vancomycin
Arm/Group Title Surotomycin Vancomycin Total
Hide Arm/Group Description 250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days 125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days Total of all reporting groups
Overall Number of Baseline Participants 308 298 606
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 308 participants 298 participants 606 participants
61.5  (17.5) 61.8  (18.4) 61.6  (17.9)
Age, Customized   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
< 75 years old Number Analyzed 290 participants 280 participants 570 participants
211 200 411
>= 75 years old Number Analyzed 290 participants 280 participants 570 participants
79 80 159
[1]
Measure Description: Number of participants <75 or >=75 years old at First Dose
[2]
Measure Analysis Population Description: Randomized participants with Confirmed CDAD
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 298 participants 606 participants
Female
185
  60.1%
175
  58.7%
360
  59.4%
Male
123
  39.9%
123
  41.3%
246
  40.6%
Previous episodes of CDAD   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
0 Previous Episodes Number Analyzed 286 participants 275 participants 561 participants
237 224 461
>= 1 Previous Episodes Number Analyzed 286 participants 275 participants 561 participants
49 51 100
[1]
Measure Description: Number of participants with previous episodes of CDAD
[2]
Measure Analysis Population Description: Randomized participants with Confirmed CDAD evaluated for previous episodes of CDAD
BI/NAP1/027 Strain   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
With BI/NAP1/027 Strain Number Analyzed 255 participants 246 participants 501 participants
59 67 126
Without BI/NAP1/027 Strain Number Analyzed 255 participants 246 participants 501 participants
196 179 375
[1]
Measure Description: Number of participants with the BI/NAP1/027 Strain
[2]
Measure Analysis Population Description: Randomized participants with Confirmed CDAD evaluated for BI/NAP1/027 Strain
1.Primary Outcome
Title Adjusted Percentage of Participants With a Clinical Outcome of Cure at the End of Treatment (EOT)
Hide Description A clinical outcome of cure at EOT was determined by resolution of diarrhea, defined as ≤ 2 loose stools per 24-hour period for at least 2 consecutive days and the lack of need for additional antibiotics to treat the current CDAD episode after completion of the study treatment period. Participants requiring a collection device were considered to have resolution of diarrhea when the volume of stool (over a 24-hour period) was decreased by 75% as compared to baseline or the participant was no longer passing liquid stool. The estimated adjusted percentage was a weighted average across all strata, constructed using Mehrotra-Railkar continuity-corrected minimum risk (MRc) stratum weights.
Time Frame Up to 13 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Microbiological Modified Intent-To-Treat (mMITT) population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 290 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
79.0
(73.9 to 83.2)
83.6
(78.8 to 87.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Non-Inferiority
Comments Surotomycin minus Vancomycin. For surotomycin to be non-inferior to vancomycin the lower bound of a 2-sided 95% CI for the difference between treatment groups had to be ≥ -10%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-11.0 to 1.9
Estimation Comments The 95% confidence interval (CI) were stratified Wilson intervals for the treatment group percentages and a stratified Newcombe interval for the treatment difference, constructed using the MRc stratum weights.
2.Primary Outcome
Title Percentage of Participants With at Least One Adverse Event (AE)
Hide Description An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. AEs may be new events or may be pre-existing conditions that have become aggravated or have worsened in severity or frequency; or may be clinically significant changes from baseline in physical examination, laboratory tests, or other diagnostic investigation (e.g. laboratory results, x-ray findings).
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 305 286
Measure Type: Number
Unit of Measure: Percentage of participants
48.5 55.2
3.Primary Outcome
Title Percentage of Participants With at Least One Serious Adverse Event (SAE)
Hide Description A SAE is any adverse experience occurring at any dose that results in any of the following outcomes: death; a life-threatening experience, referring to a situation in which the participant was at risk of death at the time of the event, requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is considered to be an important medical event.
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 305 286
Measure Type: Number
Unit of Measure: Percentage of participants
14.4 12.9
4.Primary Outcome
Title Percentage of Participants Who Discontinued Treatment Due to an AE
Hide Description An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. AEs may be new events or may be pre-existing conditions that have become aggravated or have worsened in severity or frequency; or may be clinically significant changes from baseline in physical examination, laboratory tests, or other diagnostic investigation (e.g. laboratory results, x-ray findings).
Time Frame Up to Day 13
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of study drug
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 305 286
Measure Type: Number
Unit of Measure: Percentage of participants
5.6 2.8
5.Secondary Outcome
Title Number of Participants With Clinical Response Over Time
Hide Description Clinical response over time as measured by those without treatment failure, recurrence, death, or lost to follow-up, measured as the number of participants without failure events (survivors) through the end of therapy (reported for Day 14) and from end of therapy to Day 40 (reported for Day 41).
Time Frame Up to Day 41
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mMITT population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 290 280
Measure Type: Count of Participants
Unit of Measure: Participants
Day 14
227
  78.3%
231
  82.5%
Day 41
147
  50.7%
151
  53.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Stratified log-rank test p-value
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.832
Comments Log-rank test of equality of survival times, stratified by age group (< 75, >= 75 years) and number of CDAD episodes (0, >= 1). Significance cut-off = 0.05
Method Log Rank
Comments [Not Specified]
6.Secondary Outcome
Title Adjusted Percentage of Participants With Sustained Clinical Response at the End of Study
Hide Description Sustained clinical response at the end of study was achieved by participants who had a clinical outcome of cure at the end of treatment (Days 40-50) and did not experience a recurrence of CDAD, did not die, were not lost to follow-up, and did not have end of study visit prior to Day 40. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mMITT population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 290 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
60.6
(55.0 to 66.0)
61.4
(55.9 to 66.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-8.8 to 7.1
Estimation Comments The 95% CI was stratified Wilson intervals for group percentages and a stratified Newcombe interval for the difference, using the MRc stratum weights. Stratified by age group and number of CDAD episodes.
7.Secondary Outcome
Title Adjusted Percentage of Participants With Sustained Clinical Response at Day 24
Hide Description Sustained clinical response at Day 24 was defined as participants who had a clinical outcome of cure at Day 24, who did not experience a recurrence of CDAD, did not die, were not lost to follow-up. Only the first failure event was counted per participant. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Day 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mMITT population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 290 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
66.6
(61.1 to 71.8)
66.1
(60.5 to 71.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-7.2 to 8.3
Estimation Comments The 95% CI was stratified Wilson intervals for group percentages and a stratified Newcombe interval for the difference, using the MRc stratum weights. Stratified by age group and number of CDAD episodes.
8.Secondary Outcome
Title Adjusted Percentage of Participants With Recurrence of CDAD at End of Study
Hide Description Participants with recurrences were defined as those who were cured at the end of therapy and had a recurrence or were lost to follow-up, died or had a Day 40 -50 contact prior to Day 40. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mMITT population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 290 280
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
17.7
(13.8 to 22.4)
21.2
(16.9 to 26.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-10.0 to 3.0
Estimation Comments The 95% CI was stratified Wilson intervals for group percentages and a stratified Newcombe interval for the difference, using the MRc stratum weights. Stratified by age group and number of CDAD episodes.
9.Secondary Outcome
Title Time to Resolution of Diarrhea
Hide Description Time to resolution of diarrhea with =< 2 unformed bowel movements (UBM) per 24-hour period was calculated as the date/time of last UBM minus the date/time of the first dose of study drug.
Time Frame Up to Day 13
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mMITT population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 290 280
Median (95% Confidence Interval)
Unit of Measure: Days
2.8
(2.2 to 3.3)
3.0
(2.2 to 3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Stratified Log-Rank p-Value
Type of Statistical Test Superiority
Comments Surotomycin was superior to vancomycin if the p-value was less than 0.05
Statistical Test of Hypothesis P-Value 0.431
Comments Log-rank test of equality of survival times, stratified by age group (< 75, >= 75 years) and number of CDAD episodes (0, >= 1). Significance cut-off = 0.05
Method Log Rank
Comments [Not Specified]
10.Secondary Outcome
Title Time to Reappearance of Diarrhea From End of Treatment to the End of Study
Hide Description Time to reappearance of diarrhea with >= 3 UBM per 24-hour period was calculated as the last date/time of study drug dose to the date/time of first reappearance of 3 or more UBMs among participants who were cured at end of treatment.
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The mMITT population consisting of all randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized; and were cured at end of treatment.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg; and Placebo over encapsulated tablet administered orally, twice daily for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 229 234
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The median value was not achieved
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Stratified Log-Rank p-Value
Type of Statistical Test Superiority
Comments Surotomycin was superior to vancomycin if the p-value was less than 0.05
Statistical Test of Hypothesis P-Value 0.011
Comments Log-rank test of equality of survival times, stratified by age group (< 75, >= 75 years) and number of CDAD episodes (0, >= 1). Significance cut-off = 0.05
Method Log Rank
Comments [Not Specified]
11.Secondary Outcome
Title Adjusted Percentage of Participants With a Clinical Response at the End of Treatment for Infections Deemed to be Caused by the C. Difficile BI/NAP1/027 Strain at Baseline
Hide Description Clinical response corresponded to a clinical outcome of cure at the end of treatment, and was achieved by participants with infections deemed to be caused by the C. difficile BI/NAP1/027 strain at baseline, who did not fail treatment, did not die, or were not lost to follow-up at the end of treatment. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Up to Day 13
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized; and with infections deemed to be caused by the C. difficile BI/NAP1/027 strain at baseline.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 59 67
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
88.5
(75.8 to 92.4)
86.3
(76.2 to 92.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-10.7 to 14.8
Estimation Comments Treatment group percentages were stratified by age group (< 75, ≥ 75) and number of previous CDAD episodes (0, ≥ 1). The 95% CIs were stratified Wilson intervals for the treatment group percentages.
12.Secondary Outcome
Title Adjusted Percentage of Participants Per Protocol 1 Population With a Clinical Response at the End of Treatment
Hide Description Clinical response corresponded to a clinical outcome of cure at the end of treatment, and was achieved by participants who did not fail treatment, did not die, or were not lost to follow-up at the end of treatment. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Up to Day 13
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed is the Per Protocol 1 (PP1) population composed of participants from the mMITT population, according to the actual treatment they received; without any protocol deviations from enrollment through 2 days after end of treatment, which could affect the efficacy conclusions.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 252 243
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
89.1
(84.5 to 92.2)
91.5
(87.2 to 94.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-7.8 to 3.0
Estimation Comments Treatment group proportions were stratified by age group (< 75, ≥ 75) and number of previous CDAD episodes (0, ≥1). The 95% CIs were stratified Wilson intervals for the treatment group proportions.
13.Secondary Outcome
Title Adjusted Percentage of Participants With a Sustained Clinical Response at the End of Study for Infections Deemed to be Caused by the C. Difficile BI/NAP1/027 Strain at Baseline
Hide Description Sustained clinical response at the end of study was achieved by participants with infections deemed to be caused by the C. difficile BI/NAP1/027 strain at baseline, who had a clinical outcome of cure at the end of treatment (Day 13) and did not experience a recurrence of CDAD, did not die, were not lost to follow-up, and did not have end of study visit prior to Day 40. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had a confirmed diagnosis of CDAD regardless of whether they received any amount of study drug, based on the treatment to which they were randomized; and with infections deemed to be caused by the C. difficile BI/NAP1/027 strain at baseline
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 59 67
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
66.1
(53.6 to 76.7)
51.5
(40.5 to 63.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value 14.6
Confidence Interval (2-Sided) 95%
-2.7 to 30.7
Estimation Comments Treatment group percentages were stratified by age group (< 75, ≥ 75) and number of previous CDAD episodes (0, ≥ 1). The 95% CIs were stratified Wilson intervals for the treatment group percentages.
14.Secondary Outcome
Title Adjusted Percentage of Participants From the Per Protocol 2 Population With a Sustained Clinical Response at the End of Study
Hide Description Sustained clinical response at the end of study was achieved by participants who had a clinical outcome of cure at the end of treatment (Days 40-50) and did not experience a recurrence of CDAD, did not die, were not lost to follow-up, and did not have end of study visit prior to Day 40. Only the first failure event per participant was counted. The estimated adjusted percentage was a weighted average across all strata, constructed using MRc stratum weights.
Time Frame Up to Day 50
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol 2 (PP2) population composed of cures and failures from the PP1 population. Additionally, to be included in the PP2 population, PP1 participants who were cured at end of treatment must not have had any protocol deviations which could affect the assessment of recurrence and have had follow-up contact through at least Day 40.
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description:
250 mg Surotomycin over encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg for 10 days
125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Overall Number of Participants Analyzed 233 227
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
70.8
(64.8 to 76.2)
66.5
(60.6 to 72.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surotomycin, Vancomycin
Comments Difference in percentage of participants
Type of Statistical Test Superiority
Comments Surotomycin - Vancomycin. For surotomycin to be considered superior to vancomycin the lower bound of the 2-sided 95% CI had to be > 0%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
-4.2 to 12.7
Estimation Comments Treatment group proportions were stratified by age group (< 75, ≥ 75) and number of previous CDAD episodes (0, ≥1). The 95% CIs were stratified Wilson intervals for the treatment group proportions.
Time Frame All AEs were collected up to Day 13; only SAEs and drug related AEs were collected thereafter 30 days after end of treatment (up to Day 50)
Adverse Event Reporting Description All randomized participants who received any amount of study drug.
 
Arm/Group Title Surotomycin Vancomycin
Hide Arm/Group Description 250 mg Surotomycin over-encapsulated tablet administered orally, twice daily for a daily total dose of 500 for 10 days 125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
All-Cause Mortality
Surotomycin Vancomycin
Affected / at Risk (%) Affected / at Risk (%)
Total   18/305 (5.90%)      9/286 (3.15%)    
Show Serious Adverse Events Hide Serious Adverse Events
Surotomycin Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/305 (14.43%)      37/286 (12.94%)    
Blood and lymphatic system disorders     
Anaemia  1  3/305 (0.98%)  3 0/286 (0.00%)  0
Febrile neutropenia  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Leukopenia  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Cardiac disorders     
Angina pectoris  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Atrial fibrillation  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Cardiac arrest  1  3/305 (0.98%)  4 1/286 (0.35%)  1
Cardiac failure  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Cardiac failure congestive  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Cardio-respiratory arrest  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Ventricular fibrillation  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Ventricular tachycardia  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Gastrointestinal disorders     
Abdominal wall haematoma  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Ascites  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Diarrhoea  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Duodenal ulcer haemorrhage  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Ileus  1  2/305 (0.66%)  2 0/286 (0.00%)  0
Inguinal hernia, obstructive  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Intestinal ischaemia  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Irritable bowel syndrome  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Jejunal ulcer perforation  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Megacolon  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Nausea  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Oesophagitis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Pancreatitis  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Vomiting  1  0/305 (0.00%)  0 1/286 (0.35%)  1
General disorders     
Death  1  1/305 (0.33%)  1 1/286 (0.35%)  1
Pyrexia  1  1/305 (0.33%)  1 1/286 (0.35%)  1
Sudden cardiac death  1  2/305 (0.66%)  2 1/286 (0.35%)  1
Hepatobiliary disorders     
Hepatorenal syndrome  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Infections and infestations     
Abscess  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Arthritis bacterial  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Bronchitis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Bronchopneumonia  1  1/305 (0.33%)  1 1/286 (0.35%)  1
Cellulitis  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Device related sepsis  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Escherichia sepsis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Escherichia urinary tract infection  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Fungal peritonitis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Gastroenteritis  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Gastroenteritis viral  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Lobar pneumonia  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Peritonitis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Peritonitis bacterial  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Pneumonia  1  3/305 (0.98%)  3 1/286 (0.35%)  1
Pseudomembranous colitis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Sepsis  1  2/305 (0.66%)  2 0/286 (0.00%)  0
Septic shock  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Strongyloidiasis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Urinary tract infection  1  1/305 (0.33%)  1 2/286 (0.70%)  2
Urosepsis  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Fall  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Hip fracture  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Lumbar vertebral fracture  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  1/305 (0.33%)  1 3/286 (1.05%)  3
Hypoglycaemia  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Hypokalaemia  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Systemic lupus erythematosus  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Lung neoplasm malignant  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Plasma cell myeloma  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Nervous system disorders     
Hypoxic-ischaemic encephalopathy  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Syncope  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Tonic convulsion  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Psychiatric disorders     
Suicidal ideation  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Renal and urinary disorders     
Hydronephrosis  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Renal failure  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Renal failure acute  1  1/305 (0.33%)  1 2/286 (0.70%)  2
Renal failure chronic  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Chronic obstructive pulmonary disease  1  1/305 (0.33%)  1 3/286 (1.05%)  3
Dyspnoea exertional  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Lung disorder  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Pneumonia aspiration  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Pulmonary embolism  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Respiratory failure  1  1/305 (0.33%)  1 2/286 (0.70%)  2
Vascular disorders     
Deep vein thrombosis  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Hypertensive emergency  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Hypotension  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Peripheral vascular disorder  1  0/305 (0.00%)  0 1/286 (0.35%)  1
Shock haemorrhagic  1  1/305 (0.33%)  1 0/286 (0.00%)  0
Venous thrombosis limb  1  1/305 (0.33%)  1 0/286 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0
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%
Surotomycin Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/305 (12.46%)      38/286 (13.29%)    
Gastrointestinal disorders     
Abdominal pain  1  16/305 (5.25%)  20 6/286 (2.10%)  6
Nausea  1  20/305 (6.56%)  23 21/286 (7.34%)  21
Nervous system disorders     
Headache  1  12/305 (3.93%)  13 18/286 (6.29%)  21
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01597505     History of Changes
Other Study ID Numbers: 4261-005
LCD-CDAD-10-07 ( Other Identifier: Cubist Study Number )
MK-4261-005 ( Other Identifier: Merck Protocol Number )
2012-000252-34 ( EudraCT Number )
First Submitted: May 10, 2012
First Posted: May 14, 2012
Results First Submitted: January 18, 2018
Results First Posted: February 28, 2018
Last Update Posted: September 11, 2018