Study of CB-183,315 in Participants With Clostridium Difficile Infection

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