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