A Study of CB-183,315 in Participants With Clostridium Di... | NCT01598311

NCT01598311

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description
LCD-CDAD-11-06	Other Identifier	Cubist Protocol Number
MK-4261-006	Other Identifier	Merck Protocol Number
2012-000252-34	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CB-183,315	Experimental	Participants took CB-183,315 250 mg twice daily (b.i.d.) and placebo capsules b.i.d. by mouth for 10 days.	Drug: CB-183,315 Drug: Placebo
Vancomycin	Active Comparator	Participants took vancomycin 125 mg four times daily (q.i.d.) by mouth for 10 days.	Drug: Vancomycin

Name	Type	Description	Arm Group Labels	Other Names
CB-183,315	Drug	CB-183,315 250 mg white coated tablet over-encapsulated in a size 00 opaque hard gelatin capsule.	CB-183,315

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT)	The percentage of participants considered "cured" (i.e., ≤2 loose stools per 24 hour period for at least 2 consecutive days and no need for additional antibiotics during the 3 days following EOT) was determined in the mMITT population. A CDAD diagnosis was defined as: 1) diarrhea with a minimum of 3 unformed bowel movements (UBM) or >200 mL volume of stool for participants with a collection device (e.g., rectal tube or colostomy bag) over 24 hours; and 2) a positive result for Clostridium difficile toxin by enzyme immunoassay (EIA), polymerase chain reaction (PCR), or a cell culture cytotoxin neutralization assay. Percentages were first stratified according to age (<75 or ≥75 years) and number of previous CDAD episodes (0 or ≥1) and constructed using Mehrotra-Railkar continuity-corrected minimum-risk stratum weights, and the weighted averages were then derived across strata in order to calculate the adjusted percentage.	Up to 3 days after EOT (up to Day 13)
Percentage of Participants Experiencing an Adverse Event (AE)	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.	Up to 30 days after EOT (up to Day 40)
Percentage of Participants Discontinuing From Study Treatment Due to an AE	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.	Up to EOT (up to Day 10)

Secondary Outcomes

Measure	Description	Time Frame
Number of Clinical Failure Events up to Day 40	The total number of clinical failure events, which included treatment failure, CDAD recurrence, death, or being lost to follow-up, occurring during each time period was determined in each arm.	Up to 30 days after EOT (up to Day 40)
Adjusted Percentage of Participants With Sustained Clinical Response at End of Study

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is able to read and sign a consent form;
Is from ≥18 to <90 years of age;
Has diarrhea, at least 3 times during one day, or 200 mL or liquid stool if using a rectal device;
Tests positive for Clostridium difficile;
If female, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study.

Exclusion Criteria:

Has toxic megacolon and/or known small bowel ileus;
Has received treatment with intravenous immune globulin (IVIG) within the past 30 days;
Has 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;
Has received a certain amount of antibacterial therapy specific for current CDAD, unless it is not working;
Has received an investigational vaccine against Clostridium difficile;
Has received an investigational product containing monoclonal antibodies against toxin A or B within 180 days;
Has more than 2 episodes of CDAD within 90 days;
Has had major gastrointestinal (GI) surgery (i.e. significant bowel resection) within 3 months (this does not include appendectomy or cholecystectomy);
Has a history of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis;
Is unable to discontinue loperamide, diphenoxylate/atropine, or cholestyramine during the duration of the study;
Is 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;
Has had stool studies positive for pathogenic ova and/or parasites;
Has an intolerance or hypersensitivity to daptomycin and/or vancomycin;
Has a life-threatening illness at the time of enrollment;
Has poor concurrent medical risks that in the opinion of the Investigator the participant should not enroll;
Has received an investigational drug or participated in any experimental procedure within 1 month;
Has human immunodeficiency virus (HIV), a cluster of differentiation (CD) 4 count <200 cells/mm^3 within 6 months of start of study therapy;
Anticipates that certain antibacterial therapy for a non-CDAD infection will be required for >7 days;
Is unable to discontinue Saccharomyces or similar probiotic;
Is on a concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy;
Is unable to comply with the protocol requirements;
Has any condition that, in the opinion of the Investigator, might interfere;
Is not expected to live for less than 8 weeks.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
28961905	Result	Daley P, Louie T, Lutz JE, Khanna S, Stoutenburgh U, Jin M, Adedoyin A, Chesnel L, Guris D, Larson KB, Murata Y. Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial. J Antimicrob Chemother. 2017 Dec 1;72(12):3462-3470. doi: 10.1093/jac/dkx299.
32747931

ID	Title	Description
FG000	CB-183,315	Participants took CB-183,315 250 mg twice daily (b.i.d.) and placebo b.i.d. by mouth for 10 days.
FG001	Vancomycin	Participants took vancomycin 125 mg four times daily (q.i.d.) by mouth for 10 days.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED	Randomized	FG000303 subjects FG001305 subjects
Treated	Safety Population	FG000294 subjects FG001301 subjects
Treated and Confirmed CDAD	mMITT Population	FG000285 subjects FG001292 subjects
COMPLETED		FG000256 subjects FG001244 subjects
NOT COMPLETED		FG00047 subjects FG00161 subjects

Type	Comment	Reasons
Physician Decision		FG0004 subjects FG0015 subjects
Adverse Event		FG0009 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	CB-183,315	Participants took CB-183,315 250 mg b.i.d. and placebo b.i.d. by mouth for 10 days.
BG001	Vancomycin	Participants took vancomycin 125 mg q.i.d. by mouth for 10 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT)	The percentage of participants considered "cured" (i.e., ≤2 loose stools per 24 hour period for at least 2 consecutive days and no need for additional antibiotics during the 3 days following EOT) was determined in the mMITT population. A CDAD diagnosis was defined as: 1) diarrhea with a minimum of 3 unformed bowel movements (UBM) or >200 mL volume of stool for participants with a collection device (e.g., rectal tube or colostomy bag) over 24 hours; and 2) a positive result for Clostridium difficile toxin by enzyme immunoassay (EIA), polymerase chain reaction (PCR), or a cell culture cytotoxin neutralization assay. Percentages were first stratified according to age (<75 or ≥75 years) and number of previous CDAD episodes (0 or ≥1) and constructed using Mehrotra-Railkar continuity-corrected minimum-risk stratum weights, and the weighted averages were then derived across strata in order to calculate the adjusted percentage.	The analysis population consists of all randomized and treated participants with a confirmed CDAD diagnosis (mMITT population).	Posted		Number	95% Confidence Interval	Adjusted percentage of participants		Up to 3 days after EOT (up to Day 13)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CB-183,315	Participants took CB-183,315 250 mg b.i.d. and placebo b.i.d. by mouth for 10 days.

ID	Term
D003015	Clostridium Infections
D003967	Diarrhea

ID	Term
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
D006020	Glycopeptides
D006001	Glycoconjugates
D002241	Carbohydrates
D010455	Peptides

ID	Title	Description
OG000	CB-183,315	Participants took CB-183,315 250 mg b.i.d. and placebo b.i.d. by mouth for 10 days.
OG001	Vancomycin	Participants took vancomycin 125 mg q.i.d. by mouth for 10 days.