Brief Summary
606 participants with Clostridium Difficile Associated Diarrhea (CDAD) participated in this study and received either oral vancomycin or CB-183,315 (surotomycin) in a blinded fashion. Treatment lasted for 10 days and participants were followed up for at least 40 days and a maximum of 100 days. The purpose of this study was to evaluate how well surotomycin treats CDAD as compared to vancomycin.
Brief Title
Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-005)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Clostridium Difficile Infection
Eligibility Criteria
To be included in this study, participants must:
* Sign a consent form;
* Be \>= 18 and \< 90 years of age;
* Have diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
* Test positive for Clostridium difficile;
* If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.
Participants will not be allowed into the study if they:
* Have toxic megacolon and/or known small bowel ileus;
* Have received treatment with intravenous immune globulin (IVIG) within the past 30 days;
* Have received treatment with a fecal transplant within 7 days, and/or if the doctor anticipates to give the participant a fecal transplant during the study;
* Have received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
* Have received an investigational vaccine against C. difficile;
* Have received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
* Had more than 2 episodes of CDAD within 90 days;
* Had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
* Have history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
* Are unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
* Are unable to discontinue opiate treatment unless on a stable dose;
* Has known positive stool cultures for other enteropathogens including but not limited to Salmonella, Shigella, and Campylobacter;
* Had stool studies positive for pathogenic ova and/or parasites;
* Have an intolerance or hypersensitivity to daptomycin and/or vancomycin;
* Have life-threatening illness at the time of enrollment;
* Have poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
* Have received an investigational drug or participated in any experimental procedure within 1 month;
* Have human immunodeficiency virus (HIV), a cluster of differentiation 4 (CD4) \< 200 cells/mm3 within 6 months of start of study therapy;
* Anticipate that certain antibacterial therapy for a non-CDAD infection will be required for \> 7 days;
* Are unable to discontinue Saccharomyces or similar probiotic;
* Are on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
* Are unable to comply with the protocol requirements;
* Have any condition that, in the opinion of the Investigator, might interfere;
* Are not expected to live for less than 8 weeks.
* Sign a consent form;
* Be \>= 18 and \< 90 years of age;
* Have diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
* Test positive for Clostridium difficile;
* If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.
Participants will not be allowed into the study if they:
* Have toxic megacolon and/or known small bowel ileus;
* Have received treatment with intravenous immune globulin (IVIG) within the past 30 days;
* Have received treatment with a fecal transplant within 7 days, and/or if the doctor anticipates to give the participant a fecal transplant during the study;
* Have received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
* Have received an investigational vaccine against C. difficile;
* Have received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
* Had more than 2 episodes of CDAD within 90 days;
* Had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
* Have history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
* Are unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
* Are unable to discontinue opiate treatment unless on a stable dose;
* Has known positive stool cultures for other enteropathogens including but not limited to Salmonella, Shigella, and Campylobacter;
* Had stool studies positive for pathogenic ova and/or parasites;
* Have an intolerance or hypersensitivity to daptomycin and/or vancomycin;
* Have life-threatening illness at the time of enrollment;
* Have poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
* Have received an investigational drug or participated in any experimental procedure within 1 month;
* Have human immunodeficiency virus (HIV), a cluster of differentiation 4 (CD4) \< 200 cells/mm3 within 6 months of start of study therapy;
* Anticipate that certain antibacterial therapy for a non-CDAD infection will be required for \> 7 days;
* Are unable to discontinue Saccharomyces or similar probiotic;
* Are on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
* Are unable to comply with the protocol requirements;
* Have any condition that, in the opinion of the Investigator, might interfere;
* Are not expected to live for less than 8 weeks.
Inclusion Criteria
To be included in this study, participants must:
* Sign a consent form;
* Be \>= 18 and \< 90 years of age;
* Have diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
* Test positive for Clostridium difficile;
* If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.
Participants will not be allowed into the study if they:
* Have toxic megacolon and/or known small bowel ileus;
* Have received treatment with intravenous immune globulin (IVIG) within the past 30 days;
* Have received treatment with a fecal transplant within 7 days, and/or if the doctor anticipates to give the participant a fecal transplant during the study;
* Have received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
* Have received an investigational vaccine against C. difficile;
* Have received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
* Had more than 2 episodes of CDAD within 90 days;
* Had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
* Have history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
* Are unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
* Are unable to discontinue opiate treatment unless on a stable dose;
* Has known positive stool cultures for other enteropathogens including but not limited to Salmonella, Shigella, and Campylobacter;
* Had stool studies positive for pathogenic ova and/or parasites;
* Have an intolerance or hypersensitivity to daptomycin and/or vancomycin;
* Have life-threatening illness at the time of enrollment;
* Have poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
* Have received an investigational drug or participated in any experimental procedure within 1 month;
* Have human immunodeficiency virus (HIV), a cluster of differentiation 4 (CD4) \< 200 cells/mm3 within 6 months of start of study therapy;
* Anticipate that certain antibacterial therapy for a non-CDAD infection will be required for \> 7 days;
* Are unable to discontinue Saccharomyces or similar probiotic;
* Are on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
* Are unable to comply with the protocol requirements;
* Have any condition that, in the opinion of the Investigator, might interfere;
* Are not expected to live for less than 8 weeks.
* Sign a consent form;
* Be \>= 18 and \< 90 years of age;
* Have diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
* Test positive for Clostridium difficile;
* If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.
Participants will not be allowed into the study if they:
* Have toxic megacolon and/or known small bowel ileus;
* Have received treatment with intravenous immune globulin (IVIG) within the past 30 days;
* Have received treatment with a fecal transplant within 7 days, and/or if the doctor anticipates to give the participant a fecal transplant during the study;
* Have received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
* Have received an investigational vaccine against C. difficile;
* Have received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
* Had more than 2 episodes of CDAD within 90 days;
* Had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
* Have history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
* Are unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
* Are unable to discontinue opiate treatment unless on a stable dose;
* Has known positive stool cultures for other enteropathogens including but not limited to Salmonella, Shigella, and Campylobacter;
* Had stool studies positive for pathogenic ova and/or parasites;
* Have an intolerance or hypersensitivity to daptomycin and/or vancomycin;
* Have life-threatening illness at the time of enrollment;
* Have poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
* Have received an investigational drug or participated in any experimental procedure within 1 month;
* Have human immunodeficiency virus (HIV), a cluster of differentiation 4 (CD4) \< 200 cells/mm3 within 6 months of start of study therapy;
* Anticipate that certain antibacterial therapy for a non-CDAD infection will be required for \> 7 days;
* Are unable to discontinue Saccharomyces or similar probiotic;
* Are on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
* Are unable to comply with the protocol requirements;
* Have any condition that, in the opinion of the Investigator, might interfere;
* Are not expected to live for less than 8 weeks.
Gender
All
Gender Based
false
Keywords
CDAD
Clostridium difficile Associated Diarrhea
CDI
Clostridium difficile Infection
Diarrhea
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
90 Years
Minimum Age
18 Years
NCT Id
NCT01597505
Org Class
Industry
Org Full Name
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Org Study Id
4261-005
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-Blinded, Active-Controlled Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea
Primary Outcomes
Outcome 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.
Outcome Measure
Adjusted Percentage of Participants With a Clinical Outcome of Cure at the End of Treatment (EOT)
Outcome Time Frame
Up to 13 days
Outcome 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).
Outcome Measure
Percentage of Participants With at Least One Adverse Event (AE)
Outcome Time Frame
Up to Day 50
Outcome 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.
Outcome Measure
Percentage of Participants With at Least One Serious Adverse Event (SAE)
Outcome Time Frame
Up to Day 50
Outcome 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).
Outcome Measure
Percentage of Participants Who Discontinued Treatment Due to an AE
Outcome Time Frame
Up to Day 13
Secondary Ids
Secondary Id
LCD-CDAD-10-07
Secondary Id
MK-4261-005
Secondary Id
2012-000252-34
Secondary Outcomes
Outcome 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).
Outcome Time Frame
Up to Day 41
Outcome Measure
Number of Participants With Clinical Response Over Time
Outcome 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.
Outcome Time Frame
Up to Day 50
Outcome Measure
Adjusted Percentage of Participants With Sustained Clinical Response at the End of Study
Outcome 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.
Outcome Time Frame
Day 24
Outcome Measure
Adjusted Percentage of Participants With Sustained Clinical Response at Day 24
Outcome 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.
Outcome Time Frame
Up to Day 50
Outcome Measure
Adjusted Percentage of Participants With Recurrence of CDAD at End of Study
Outcome 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.
Outcome Time Frame
Up to Day 13
Outcome Measure
Time to Resolution of Diarrhea
Outcome 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.
Outcome Time Frame
Up to Day 50
Outcome Measure
Time to Reappearance of Diarrhea From End of Treatment to the End of Study
Outcome 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.
Outcome Time Frame
Up to Day 13
Outcome Measure
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
Outcome 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.
Outcome Time Frame
Up to Day 13
Outcome Measure
Adjusted Percentage of Participants Per Protocol 1 Population With a Clinical Response at the End of Treatment
Outcome 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.
Outcome Time Frame
Up to Day 50
Outcome Measure
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
Outcome 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.
Outcome Time Frame
Up to Day 50
Outcome Measure
Adjusted Percentage of Participants From the Per Protocol 2 Population With a Sustained Clinical Response at the End of Study
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
90
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Riska
Investigator Email
priska@montefiore.org
Investigator Phone
718-020-6494