A Phase 2b Trial of EPB-348 for the Treatment of Herpes Zoster

In cells infected with varicella-zoster virus, there is evidence to suggest that EPB-348
could offer clinically important advantages in the treatment of acute herpes zoster over
currently available therapies due to rapid absorption and conversion to the active moiety as
well as a longer intra-cellular half-life in infected cells. Clinically, these
characteristics could translate into once-daily dosing versus thrice-daily dosing as seen
with current therapy, leading to a higher rate of compliance and quality-of-life, especially
among elderly patients. The objective of EPB348-0201 is to determine the pharmacokinetics
and dosage of EPB-348 that best balances safety and efficacy among adult immunocompetent
patients with an acute episode of herpes zoster. This multi-center study will randomly
assign patients to either EPB-348 1000 mg once daily or EPB-348 2000 mg once daily or
valacyclovir 1000 mg three times daily.

Inclusion Criteria:

- Male and female adults at least 18 years of age

- Patients with signs and symptoms consistent with acute herpes zoster disease, namely,
a dermatomal vesicular rash which may be preceded by pain and parasthesias in the
days before vesicular eruption

- Herpes Zoster associated rash present for ≤ 72 hours

- Patients who are deemed to be immunocompetent based on history and physical exam

Exclusion Criteria:

- Females who are pregnant or nursing

- History or clinical manifestations of significant metabolic, hematological,
pulmonary, ischemic, or unstable heart disease, gastrointestinal, neurological,
psychiatric, renal, urological, endocrine, opthalmologic, or immune mediated disease
including HIV or HBsAg positivity

- Chronic genital herpes

- Patients who received cytotoxic or immunosuppressive drug therapy within 3 months
prior to study participation

- Previous vaccinations against Herpes Zoster

- Patients with > 50% of vesicles crusted at screen

- Patients who received topical or systemic antiviral medications or immunomodulatory
agents for herpes zoster viral infections or capsaicin within 4 weeks of study
participation

- Patients with a history of congenital, acquired, or corticosteroid induced
immunodeficiency, including malignancy, significantly impaired renal function
(creatinine clearance < 50 cc/min), and impaired hepatic function (ALT or AST levels
> 3 times the upper limit of normal)

- QTc > 500msec

- Patients with a history of intolerance or hypersensitivity to acyclovir, penciclovir,
valacyclovir, or famciclovir

- Patients with gastrointestinal dysfunction that might interfere with drug absorption

- Patients, considered by the investigator, for any reason, to be an unsuitable
candidate for receiving the study drug