Clostridium Difficile InfectionPhase 3NCT01598311

A Study of CB-183,315 in Participants With Clostridium Difficile Associated Diarrhea (MK-4261-006)

A Phase 3 study testing CB-183,315 and Vancomycin in people with Clostridium Difficile Infection, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

A total of 608 participants with Clostridium Difficile Associated Diarrhea (CDAD) will participate in this study; participants will receive either oral vancomycin or CB-183,315 in a blinded fashion. Treatment will last for 10 days and participants will be followed up for at least 40 days and a maximum of 100 days. Read more about this study

Who is it for?: Ages 18 to 89 years
Conditions the study is for: Clostridium Difficile Infection
What is being tested?: CB-183,315 and Vancomycin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 608 participants
Where: No sites listed yet
Study dates: 16 May 2012to 25 Aug 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 89 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

Show all 24Show fewer

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.

About this study

Official title: A Randomized, Double-Blinded, Active-Controlled Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea

Conditions: Clostridium Difficile Infection
Being tested: CB-183,315, Vancomycin, Placebo
Keywords: CDAD, Clostridium difficile Associated Diarrhea, CDI, Clostridium difficile Infection, Diarrhea
Medical subject headings: Clostridium Infections, Diarrhea

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CB-183,315Drug
Also called Surotomycin
CB-183,315 250 mg white coated tablet over-encapsulated in a size 00 opaque hard gelatin capsule.
VancomycinDrug
Vancomycin hydrochloride 125 mg capsule over-encapsulated in size 00 opaque hard gelatin capsule.
PlaceboDrug
Placebo size 00 opaque hard gelatin capsules.

Study groups in NCT01598311
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Vancomycin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Up to EOT (up to Day 10)

Secondary outcomes (2)

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.
Measured: Up to 30 days after EOT (up to Day 40)
Adjusted Percentage of Participants With Sustained Clinical Response at End of Study
The percentage of participants with sustained clinical response was determined for each arm. Sustained clinical response was declared when participants had a clinical outcome of cure at EOT, did not experience any CDAD recurrence, did not die, were not lost to follow-up, and did not have the end of study visit prior to Day 40. 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.
Measured: Up to 40 days after EOT (up to Day 50)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 May 201225 Aug 2015

First posted15 May 2012 (estimated)
Study start16 May 2012
Primary completion26 Jul 2015
Study completion25 Aug 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 608 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01598311
Sponsor's protocol ID: 4261-006
Other IDs: LCD-CDAD-11-06, MK-4261-006, 2012-000252-34
Status last verified: Aug 2022
First submitted: 10 May 2012
Last updated: 22 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 28961905
Cheknis A, Devaris D, Chesnel L, Dale SE, Nary J, Sambol SP, Citron DM, Goering RV, Johnson S. Characterization of Clostridioides difficile isolates recovered from two Phase 3 surotomycin treatment trials by restriction endonuclease analysis, PCR ribotyping and antimicrobial susceptibilities. J Antimicrob Chemother. 2020 Nov 1;75(11):3120-3125. doi: 10.1093/jac/dkaa297.
PubMed 32747931

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingObservational study
Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
Clostridioides Difficile Infection
Active, not recruitingPhase 2
Autologous Fecal Microbiota Transplantation (Auto-FMT) for Prophylaxis of Clostridium Difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
RecruitingEarly Phase 1
Prevention of Recurrence of Clostridioides Difficile Colitis With Ursodeoxycholic Acid (UCDA) as a Supplement to Standard Therapy
Clostridioides Difficile Infection

All Clostridium Difficile Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blinded, Active-Controlled Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea
ClinicalTrials.gov ID: NCT01598311
Acronym / sponsor ID: 4261-006
Conditions: Clostridium Difficile Infection
Keywords: CDAD, Clostridium difficile Associated Diarrhea, CDI, Clostridium difficile Infection, Diarrhea
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 608 participants (actual)
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: 16 May 2012 (actual)
Primary completion: 26 Jul 2015 (actual)
Study completion: 25 Aug 2015 (actual)
First posted: 15 May 2012 (estimated)
Results: Posted 27 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
CB-183,315	Experimental	Drug: CB-183,315, Drug: PlaceboParticipants took CB-183,315 250 mg twice daily (b.i.d.) and placebo capsules b.i.d. by mouth for 10 days.
Vancomycin	Active comparator	Drug: VancomycinParticipants took vancomycin 125 mg four times daily (q.i.d.) by mouth for 10 days.

Who may qualify

Ages: 18 to 89 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (24 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CB-183,315Also: SurotomycinCB-183,315 250 mg white coated tablet over-encapsulated in a size 00 opaque hard gelatin capsule.	Drug	CB-183,315
VancomycinVancomycin hydrochloride 125 mg capsule over-encapsulated in size 00 opaque hard gelatin capsule.	Drug	Vancomycin
PlaceboPlacebo size 00 opaque hard gelatin capsules.	Drug	CB-183,315

Primary outcome

Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT)
Time frame: Up to 3 days after EOT (up to Day 13)
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.
Percentage of Participants Experiencing an Adverse Event (AE)
Time frame: Up to 30 days after EOT (up to Day 40)
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.
Percentage of Participants Discontinuing From Study Treatment Due to an AE
Time frame: Up to EOT (up to Day 10)
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.

2 secondary outcomes

Number of Clinical Failure Events up to Day 40
Time frame: Up to 30 days after EOT (up to Day 40)
Adjusted Percentage of Participants With Sustained Clinical Response at End of Study
Time frame: Up to 40 days after EOT (up to Day 50)

Results and safety

Results posted to the registry on 27 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CB-183,315	303	256
Vancomycin	305	244

Primary outcome: Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT)

Time frame: Up to 3 days after EOT (up to Day 13). Number (95% Confidence Interval). Unit: Adjusted percentage of participants

Measure	CB-183,315 n = 285	Vancomycin n = 292
Value	83.4 (78.7 to 87.2)	82.1 (77.2 to 85.9)

CB-183,315 vs Vancomycin: Mean Difference (Final Values): 1.4 (95% CI -4.9 to 7.6)

Population analysed: The analysis population consists of all randomized and treated participants with a confirmed CDAD diagnosis (mMITT population).

Primary outcome: Percentage of Participants Experiencing an Adverse Event (AE)

Time frame: Up to 30 days after EOT (up to Day 40). Number. Unit: Percentage of Participants

Measure	CB-183,315 n = 294	Vancomycin n = 301
Value	52.4	60.1

Population analysed: The analysis population consists of all randomized and treated participants (Safety Population).

Primary outcome: Percentage of Participants Discontinuing From Study Treatment Due to an AE

Time frame: Up to EOT (up to Day 10). Number. Unit: Percentage of Participants

Measure	CB-183,315 n = 294	Vancomycin n = 301
Value	3.7	3.0

Population analysed: The analysis population consists of all randomized and treated participants (Safety Population).

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: All AEs were collected up to Day 13; only serious AEs (SAEs) and drug-related AEs were collected up to Day 50.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CB-183,315	33 of 294 (11.2%)	53 of 294 (18%)	9 of 294
Vancomycin	39 of 301 (13%)	72 of 301 (23.9%)	11 of 301

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28961905Daley 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.
Derived from this study: PubMed 32747931Cheknis A, Devaris D, Chesnel L, Dale SE, Nary J, Sambol SP, Citron DM, Goering RV, Johnson S. Characterization of Clostridioides difficile isolates recovered from two Phase 3 surotomycin treatment trials by restriction endonuclease analysis, PCR ribotyping and antimicrobial susceptibilities. J Antimicrob Chemother. 2020 Nov 1;75(11):3120-3125. doi: 10.1093/jac/dkaa297.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Clostridium Difficile Infection

Not yet recruitingObservational study
Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
Clostridioides Difficile Infection
Active, not recruitingPhase 2
Autologous Fecal Microbiota Transplantation (Auto-FMT) for Prophylaxis of Clostridium Difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
RecruitingEarly Phase 1
Prevention of Recurrence of Clostridioides Difficile Colitis With Ursodeoxycholic Acid (UCDA) as a Supplement to Standard Therapy
Clostridioides Difficile Infection

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CB-183,315 and Vancomycin in people with Clostridium Difficile Infection, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adjusted Percentage of Participants Meeting Clinical Response Criteria for Cure at End of Treatment (EOT) (time frame: Up to 3 days after EOT (up to Day 13)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01598311, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.