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Clostridium Difficile InfectionPhase 3NCT01597505

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

A Phase 3 study testing Surotomycin 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
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Clostridium Difficile Infection
What is being tested?
Surotomycin and Vancomycin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
606 participants
Where
No sites listed yet
Study dates
16 May 2012to 20 Mar 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 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

About this study

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

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.

Being tested
Surotomycin, 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.

  • SurotomycinDrug

    Also called CB-183,315

    250 mg Surotomycin over-encapsulated tablet administered orally, twice daily for a daily total dose of 500 mg, for 10 days

  • VancomycinDrug

    125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days

  • PlaceboDrug

    Placebo for Surotomycin over-encapsulated tablet administered orally, twice daily for 10 days

Study groups in NCT01597505
Study groupRoleWhat they receive
SurotomycinExperimental250 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
Receives: Drug: Surotomycin; Drug: Placebo
VancomycinActive comparator125 mg Vancomycin over-encapsulated capsule administered orally, four times daily for a daily total dose of 500 mg, for 10 days
Receives: Drug: Vancomycin

What is being measured

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

  1. Adjusted Percentage of Participants With a Clinical Outcome of Cure at the End of Treatment (EOT)

    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.

    Measured: Up to 13 days

  2. Percentage of Participants With at Least One 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. 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).

    Measured: Up to Day 50

  3. Percentage of Participants With at Least One Serious Adverse Event (SAE)

    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.

    Measured: Up to Day 50

  4. Percentage of Participants Who Discontinued 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. 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).

    Measured: Up to Day 13

Secondary outcomes (10)
  1. Number of Participants With Clinical Response Over Time

    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).

    Measured: Up to Day 41

  2. Adjusted Percentage of Participants With Sustained Clinical Response at the End of Study

    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.

    Measured: Up to Day 50

  3. Adjusted Percentage of Participants With Sustained Clinical Response at Day 24

    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.

    Measured: Day 24

  4. Adjusted Percentage of Participants With Recurrence of CDAD at End of Study

    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.

    Measured: Up to Day 50

  5. Time to Resolution of Diarrhea

    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.

    Measured: Up to Day 13

  6. Time to Reappearance of Diarrhea From End of Treatment to the End of Study

    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.

    Measured: Up to Day 50

  7. 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

    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.

    Measured: Up to Day 13

  8. Adjusted Percentage of Participants Per Protocol 1 Population With a Clinical Response at the End of Treatment

    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.

    Measured: Up to Day 13

  9. 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

    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.

    Measured: Up to Day 50

  10. Adjusted Percentage of Participants From the Per Protocol 2 Population With a Sustained Clinical Response at the End of Study

    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.

    Measured: 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.

  1. First posted14 May 2012 (estimated)
  2. Study start16 May 2012
  3. Primary completion20 Mar 2015
  4. Study completion20 Mar 2015

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
606 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01597505
Sponsor's protocol ID
4261-005
Other IDs
LCD-CDAD-10-07, MK-4261-005, 2012-000252-34
Status last verified
Jul 2019
First submitted
10 May 2012
Last updated
23 Jul 2019
Data monitoring committee
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Boix V, Fedorak RN, Mullane KM, Pesant Y, Stoutenburgh U, Jin M, Adedoyin A, Chesnel L, Guris D, Larson KB, Murata Y. Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection. Open Forum Infect Dis. 2017 Jan 19;4(1):ofw275. doi: 10.1093/ofid/ofw275. eCollection 2017 Winter.

    PubMed 28480267
  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Surotomycin 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?

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 23 Jul 2019. 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 28 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 With a Clinical Outcome of Cure at the End of Treatment (EOT) (time frame: Up to 13 days). The study lists 4 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 NCT01597505, 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 23 Jul 2019.

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