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

A Randomized, Double-blind, Active-controlled, Multi-center, Parallel-group Dose-ranging Study Assessing the Safety and Efficacy of EPB-348 Versus Valacyclovir Among Immunocompetent Patients With an Acute Episode of Herpes Zoster

The purpose of this study 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.

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