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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Herpes Zoster

Intervention / Treatment
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* Drug: EPB-348
* Drug: Valacyclovir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPB-348 1000 mg<br>EPB-348 1000 mg dosed once daily for seven days | Drug: EPB-348<br>* Treated over seven days<br>* Other names: Valomaciclovir Stearate;|
| Experimental: EPB-348 2000 mg<br>EPB-348 2000 mg dosed once daily for seven days | Drug: EPB-348<br>* Treated over seven days<br>* Other names: Valomaciclovir Stearate;|
| Experimental: EPB-348 3000 mg<br>EPB-348 3000 mg dosed once daily for seven days | Drug: EPB-348<br>* Treated over seven days<br>* Other names: Valomaciclovir Stearate;|
| Active Comparator: Valacyclovir<br>Valacyclovir 1000 mg dosed three times daily for seven days | Drug: Valacyclovir<br>* Treated over seven days<br>* Other names: Valtrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the time-to-crusting of vesicles on patients in each of the EPB-348 dosing arms versus the valacyclovir dosing arm. |  | Daily assessment during the seven days of treament then weekly until Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EPB348, Valomaciclovir Stearate, Valacyclovir, Herpes Zoster, Shingles