Clostridium Difficile InfectionPhase 2NCT01085591
Study of CB-183,315 in Participants With Clostridium Difficile Infection
A Phase 2 study testing CB-183,315 and Vancomycin in people with Clostridium Difficile Infection and Diarrhea, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 32 sites in 2 countries.
Trial summary
This is a randomized, double-blind, single-placebo, active-controlled, dose ranging parallel group design with 3 arms. Two dose regimens of CB-183,315 dosed twice daily will be compared with the active comparator oral vancomycin (125 milligrams (mg ) four times daily). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection, Diarrhea
- 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
- 210 participants
- Where
- 32 sitesin 2 countries
- Study dates
- 1 Apr 2010to 13 May 2011
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- A participant will not be enrolled if s/he meets any of the following criteria:
- Female and pregnant or lactating
- Toxic megacolon and/or known small bowel ileus
- Received treatment with intravenous (IV) immune globulin within 30 days prior to the first dose of study drug
- Antibacterial therapy specific for current CDI or that may be effective for CDI even if given for a different indication:
- Received more than 24 hours of oral vancomycin for the current episode of CDI prior to first dose of study drug.
Show all 39Show fewer
- Received more than 24 hours of oral/intravenous metronidazole OR any other therapy specific for the current episode of CDI immediately prior to first dose of study drug unless the participant received at least 3 days of such therapy, and is considered a treatment failure for CDI.
- Received more than 24 hours of oral/intravenous metronidazole for any other indication in the 3 days prior to first dose of study drug.
- Participants with more than 2 episodes of CDI within 90 days (that is, participants can be enrolled with their 1st recurrence/2nd episode)
- Major gastrointestinal (GI) surgery (that is, significant bowel resection including total colectomy with ileostomy) within 3 months of enrollment (this does not include appendectomy or cholecystectomy)
- History of prior inflammatory bowel disease: ulcerative colitis, Crohn's disease, or microscopic colitis
- Unable to stop loperamide, diphenoxylate, and cholestyramine during the duration of the study
- Unable to stop opiate treatment, unless on a stable dose as of onset of diarrhea and no change in dose planned for the duration of the study
- Known positive stool cultures for other enteropathogens, including but not limited to Salmonella, Shigella and Campylobacter
- Known stool studies positive for ova and/or parasites
- Known intolerance or hypersensitivity to daptomycin and/or vancomycin
- Poor concurrent medical risks with clinically significant co-morbid disease such that in the opinion of the Investigator the participant should not be enrolled
- Received an investigational drug or participated in any experimental procedure within 1 month prior to study entry
- Previously enrolled in this study
- Received an investigational vaccine against C. difficile
- Participants with known Hepatitis B or Hepatitis C who have alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal (ULN) and/or bilirubin > 1.5 times the ULN
- Human immunodeficiency virus positive, unless controlled (that is, on triple therapy) and with a CD4 > 200 cells per millimeter cubed (cellsmm˄3)
- Anticipated that systemic antibacterial therapy for a non-CDI infections will be required for >7 days after start of study therapy
- Concurrent therapy with daptomycin
- Unable to discontinue Saccharomyces or similar probiotic
- Known active IV drug or alcohol abuse
- Concurrent intensive chemotherapy, radiotherapy or biologic treatment for active malignancy (may only be enrolled after consultation with Medical Monitor)
- Unable to comply with the protocol requirements
- Any condition that, in the opinion of the Investigator, might interfere with study objectives
- Life expectancy is less than 6 weeks
- Additional Exclusions for Participants with Severe CDI
- In addition to the criteria listed above, a participant who meets the definition of severe CDI will not be enrolled if the participant meets any of the following criteria:
- Age > 80
- Hypotension, defined by sustained systolic blood pressure < 90 millimeters of mercury (mmHg), or need for vasopressors to maintain blood pressure
- Abdominal rebound tenderness on examination
- Acute kidney insufficiency defined by:
- oliguria (< 20 cubic centimeter [cc] urine output per hour over a 4 hour period not responsive to attempts to increase renal perfusion) or
- non-perfusion (for example, pre-renal) related azotemia with initial creatinine (Baseline) > 2.5 milligrams per deciliter (mg/dL) and blood urea nitrogen (BUN) > 40 mg/dL with no prior history of chronic kidney disease
- Unable to tolerate oral medications due to persistent vomiting 2. White blood cell (WBC) count > 30,000/mm˄3
Trial locations and contacts
32 sites in 2 countries.
32 sites in 2 countries
United States22 sites
Tufts University School of Medicine
Boston, Massachusetts
Mercury Street Medical Group - Research Group
Butte, Montana
Metropolitan Gastroentrology Group
Chevy Chase, Maryland
University of Chicago
Chicago, Illinois
Remington Davis Inc.
Columbus, Ohio
Atlanta Institute for Medical Research, Inc
Decatur, Georgia
Henry Ford Health System
Detroit, Michigan
MeritCare Clinical Research
Fargo, North Dakota
Idaho Falls Infectious Disease, PLLC
Idaho City, Idaho
University of Kansas Medical Center
Kansas City, Kansas
Study site
Keego Harbor, Michigan, 48320
Gastrointestinal Specialists of Georgia PC
Marietta, Georgia
Wellstar Infectious Disease
Marietta, Georgia
University of Minnesota
Minneapolis, Minnesota
Ochsner Clinic Foundation
New Orleans, Louisiana
DiGiovanna Institute for Medical Education and Research
North Massapequa, New York
William Beaumont Hospital
Royal Oak, Michigan
Central Florida Internists
Saint Cloud, Florida
Missouri Baptist Medical Center
St Louis, Missouri
Providence Hospital Clinical Research Center
Washington D.C., District of Columbia
Washington Hospital Center
Washington D.C., District of Columbia
Wake Forest University Health Sciences
Winston-Salem, North Carolina
Canada10 sites
University of Calgary, Foothills Medical Center
Calgary, Alberta
Centre de Sante et des Services Sociaux de Chicoutimi
Chicoutimi, Quebec
St. Joseph Healthcare
Hamilton, Ontario
Queen's University
Kingston, Ontario
Maisonneuve Rosemont Hospital
Montreal, Quebec
SMBD- Jewish General Hospital G-139
Montreal, Quebec
Centre Hospitalier Universitaire de Québec
Québec, Quebec
Centre Hospitalier Universitaire de Sherbrooke
Sherbrook, Quebec
Mount Sinai Hospital
Toronto, Ontario
Centre hopitalier regional de Trois-Rivieres
Trois-Rivières, Quebec
About this study
Official title: A Randomized, Double-Blinded, Active-Controlled, Dose Ranging Study of CB-183,315 in Patients With Clostridium Difficile Infection.
This is a randomized, double-blind, single-placebo, active-controlled, dose ranging parallel group design with 3 arms. Two dose regimens of CB-183,315 dosed twice daily will be compared with the active comparator oral vancomycin (125 milligrams (mg ) four times daily). Participants with diarrhea at risk for Clostridium difficile infection (CDI) [for example, received prior or concomitant antibiotic(s)] will be identified and tested for C. difficile toxin in stool using an enzyme immunoassay (EIA), or polymerase chain reaction (PCR) per the usual standard of care. Eligible participants will be consented, undergo baseline evaluations, and will be randomized in a blinded fashion to one of 3 treatment arms.
Participants will be randomized to receive either 125 mg CB-183,315 twice daily alternating with placebo tablets twice daily, 250 mg CB-183,315 twice daily alternating with placebo tablets twice daily or 125 mg oral vancomycin four times dailyover a period of 10 days in a 1:1:1 fashion.
- Conditions
- Clostridium Difficile Infection, Diarrhea
- Being tested
- CB-183,315, Placebo, Vancomycin
- Keywords
- 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
PlaceboDrug
VancomycinDrug
| Study group | Role | What they receive |
|---|---|---|
| CB-183,315, 125 mg | Experimental | 125 milligrams (mg) CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days. Receives: Drug: CB-183,315; Drug: Placebo |
| CB-183,315, 250 mg | Experimental | 250 mg CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days. Receives: Drug: CB-183,315; Drug: Placebo |
| Vancomycin, 125 mg | Active comparator | 125 mg vancomycin administered orally four times a day for 10 days. Receives: Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Clinical Response Outcome of Clostridium Difficile Infection Cure at the End of Study Treatment
The number of participants with an Investigator-assessed clinical response of cure is presented. The information to assess clinical response was collected at any time up to and including Day 19.
Measured: Baseline (Day 0) through Study Day 19
Number of Participants With a Clinical Response Outcome of Failure or Unable to Evaluate at the End of Study Treatment
The number of participants with investigator assessed clinical response of failure or unable to evaluate is presented. Clinical response was determined by the participant's condition on the second day following the last dose of study medication, unless considered a treatment failure. Treatment failures were assessed whenever they occurred and were carried forward to the end-of-treatment (EOT). The information to assess clinical response was collected at any time up to and including Day 19.
Measured: Baseline (Day 0) through Study Day 19
Secondary outcomes (4)
Number of Participants With a Recurrence of Clostridium Difficile Infection Through the 4-week Follow-up Period
The number of participants with a recurrence of CDI is presented along with the number of participants without a recurrence and who were unable to be evaluated. Participants with a favorable outcome at the EOT (cure) were evaluated for recurrence of CDI. Only subjects deemed a cure at EOT were assessed for recurrence. This is the denominator used for all percentages. If diarrheal symptoms returned, participants were asked to indicate the number of unformed bowel movements (UBM) they had and have an additional C. difficile toxin test. The information to assess recurrence in participants who were deemed a cure at EOT was collected at any time during the 4-week Follow-up Period (FUP).
Measured: Study Day 10 up to Study Day 40
Number of Participants With a Clinical Response Outcome at the End of Study Treatment With and Without Infection Caused by C. Difficile BI/NAP1/027 Strain at Baseline
The number of participants with investigator assessed clinical response of cure, failure or unable to evaluate is presented and shown separately for participants with and without infection caused by C. difficile BI/NAP1/027 strain as determined at baseline. Clinical response was determined by the participant's condition on the second day following the last dose of study medication, unless considered a treatment failure. Treatment failures were assessed whenever they occurred and were carried forward to the EOT. The information to assess clinical response for infection caused by C. difficile BI/NAP1/027 strain at Baseline was collected at any time up to and including Day 12. Strain at Baseline=SAB
Measured: Baseline (Day 0) through Study Day 12
Number of Participants With a Recurrence of Clostridium Difficile Infection at the End of Study Treatment With and Without Infection Caused by C. Difficile BI/NAP1/027 Strain at Baseline
The number of participants with and without infection caused by C. difficile BI/NAP1/027 strain as determined at baseline with a recurrence of CDI is presented along with the number of participants without a recurrence and who were unable to be evaluated. Participants with a favorable outcome at the EOT (cure) were evaluated for recurrence of CDI. If diarrheal symptoms returned, participants were asked to indicate the number of UBM they had and have an additional C. difficile toxin test. The information to assess recurrence in participants who were deemed a cure at EOT was collected at any time during the 4-week FUP. Strain at Baseline=SAB.
Measured: Study Day 10 up to Study Day 40
Median Time to Resolution of Diarrhea
The median time to resolution of diarrhea is presented for evaluable participants in each treatment group. The time in days from the start of treatment (time of first dose of study drug) to resolution (time of the last UBM on the day before the first of 2 consecutive days of < 4 UBMs and sustained through the second day following the last dose of study drug).
Measured: Baseline (Day 0) through Study Day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2010 (estimated)
- Study start1 Apr 2010
- Primary completion13 Apr 2011
- Study completion13 May 2011
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 (1)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01085591
- Sponsor's protocol ID
- 4261-007
- Other IDs
- LCD-DR-09-03
- Status last verified
- Aug 2018
- First submitted
- 9 Mar 2010
- Last updated
- 11 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Lee CH, Patino H, Stevens C, Rege S, Chesnel L, Louie T, Mullane KM. Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother. 2016 Oct;71(10):2964-71. doi: 10.1093/jac/dkw246. Epub 2016 Jul 17.
PubMed 27432604
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded, Active-Controlled, Dose Ranging Study of CB-183,315 in Patients With Clostridium Difficile Infection.
- ClinicalTrials.gov ID
- NCT01085591
- Acronym / sponsor ID
- 4261-007
- Conditions
- Clostridium Difficile Infection, Diarrhea
- Keywords
- CDI, Clostridium difficile Infection, Diarrhea
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 1 Apr 2010 (actual)
- Primary completion
- 13 Apr 2011 (actual)
- Study completion
- 13 May 2011 (actual)
- First posted
- 12 Mar 2010 (estimated)
- Results
- Posted 16 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, single-placebo, active-controlled, dose ranging parallel group design with 3 arms. Two dose regimens of CB-183,315 dosed twice daily will be compared with the active comparator oral vancomycin (125 milligrams (mg ) four times daily). Participants with diarrhea at risk for Clostridium difficile infection (CDI) [for example, received prior or concomitant antibiotic(s)] will be identified and tested for C. difficile toxin in stool using an enzyme immunoassay (EIA), or polymerase chain reaction (PCR) per the usual standard of care. Eligible participants will be consented, undergo baseline evaluations, and will be randomized in a blinded fashion to one of 3 treatment arms.
Participants will be randomized to receive either 125 mg CB-183,315 twice daily alternating with placebo tablets twice daily, 250 mg CB-183,315 twice daily alternating with placebo tablets twice daily or 125 mg oral vancomycin four times dailyover a period of 10 days in a 1:1:1 fashion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CB-183,315, 125 mg | Experimental | Drug: CB-183,315, Drug: Placebo125 milligrams (mg) CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days. |
| CB-183,315, 250 mg | Experimental | Drug: CB-183,315, Drug: Placebo250 mg CB 183,315 administered orally twice daily, alternating with twice daily oral administration of placebo tablets, for 10 days. |
| Vancomycin, 125 mg | Active comparator | Drug: Vancomycin125 mg vancomycin administered orally four times a day for 10 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (39 listed)
- Female and pregnant or lactating
- Toxic megacolon and/or known small bowel ileus
- Received treatment with intravenous (IV) immune globulin within 30 days prior to the first dose of study drug
- Antibacterial therapy specific for current CDI or that may be effective for CDI even if given for a different indication:
- Participants with more than 2 episodes of CDI within 90 days (that is, participants can be enrolled with their 1st recurrence/2nd episode)
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-183,315 | Drug | CB-183,315, 125 mg, CB-183,315, 250 mg |
| Placebo | Drug | CB-183,315, 125 mg, CB-183,315, 250 mg |
| Vancomycin | Drug | Vancomycin, 125 mg |
Primary outcome
Number of Participants With a Clinical Response Outcome of Clostridium Difficile Infection Cure at the End of Study Treatment
Time frame: Baseline (Day 0) through Study Day 19
The number of participants with an Investigator-assessed clinical response of cure is presented. The information to assess clinical response was collected at any time up to and including Day 19.
Number of Participants With a Clinical Response Outcome of Failure or Unable to Evaluate at the End of Study Treatment
Time frame: Baseline (Day 0) through Study Day 19
The number of participants with investigator assessed clinical response of failure or unable to evaluate is presented. Clinical response was determined by the participant's condition on the second day following the last dose of study medication, unless considered a treatment failure. Treatment failures were assessed whenever they occurred and were carried forward to the end-of-treatment (EOT). The information to assess clinical response was collected at any time up to and including Day 19.
4 secondary outcomes
Number of Participants With a Recurrence of Clostridium Difficile Infection Through the 4-week Follow-up Period
Time frame: Study Day 10 up to Study Day 40
Number of Participants With a Clinical Response Outcome at the End of Study Treatment With and Without Infection Caused by C. Difficile BI/NAP1/027 Strain at Baseline
Time frame: Baseline (Day 0) through Study Day 12
Number of Participants With a Recurrence of Clostridium Difficile Infection at the End of Study Treatment With and Without Infection Caused by C. Difficile BI/NAP1/027 Strain at Baseline
Time frame: Study Day 10 up to Study Day 40
Median Time to Resolution of Diarrhea
Time frame: Baseline (Day 0) through Study Day 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27432604Lee CH, Patino H, Stevens C, Rege S, Chesnel L, Louie T, Mullane KM. Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother. 2016 Oct;71(10):2964-71. doi: 10.1093/jac/dkw246. Epub 2016 Jul 17.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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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.
The record lists no contact. Use the official record to reach the sponsor.
32 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CB-183,315 and Vancomycin in people with Clostridium Difficile Infection and Diarrhea, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 32 sites in 2 countries.
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 0 inclusion and 39 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 11 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Jun 2015). 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?
Number of Participants With a Clinical Response Outcome of Clostridium Difficile Infection Cure at the End of Study Treatment (time frame: Baseline (Day 0) through Study Day 19). The study lists 2 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 NCT01085591, which also lists 1 linked publication.
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 11 Sep 2018.