Clinical trial NCT01085591 (phase 2, status: completed)
Conditions: clostridium difficile infection, diarrhea
ICD codes: A05.2, A04.71, A04.72, B96.7, K59.1, R19.7, P78.3, K58.0, K58.9
Drugs: cb-183,315, placebo, vancomycin
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)C2=C(N)C=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O
Eligibility criteria:

        To be eligible for enrollment, a participant must meet all of the following criteria prior
        to any study related procedures:

          -  Informed Consent obtained and signed

          -  Age ≥ 18 years

          -  If female, participant is non-lactating, and is either:

               -  Not of childbearing potential, defined as postmenopausal for at least 1 year or
                  surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or
                  hysterectomy

               -  Of childbearing potential and is practicing the barrier method of birth control
                  along with one of the following methods: oral or parenteral contraceptives for 3
                  months prior to study drug administration, a vasectomized partner, or abstinence
                  from sexual intercourse

          -  Established non-severe or severe CDI (after Data Monitoring Committee [DMC] review)
             with a positive stool test for toxin A and/or B within 72 hours prior to first dose of
             study drug.

        Exclusion Criteria:

        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.

               -  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