A Study Comparing Daily Treatment With Valaciclovir To Placebo For Suppression Of Herpes Simplex Virus HSV-2 Genital Herpes In Newly Diagnosed Patients. VALTREX® Tablet is a Trademark of the GlaxoSmithKline Group of Companies.

Study Overview
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Brief Summary
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Genital herpes (GH) is a commonly occurring sexually transmitted disease caused by herpes simplex virus (HSV). There are two types of HSV, type 1 (HSV-1) and type 2 (HSV-2); both can cause GH, although the latter is much more likely to produce frequent recurrences of GH lesions. Evidence suggests that there are advantages to using suppressive vs. episodic treatment, which include increased intervals between the pain and discomfort of genital herpes recurrences. Therefore, this study will collect safety and efficacy data on suppressive therapy with valaciclovir in subjects newly diagnosed with HSV-2 genital herpes.

Official Title
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An International, Randomized, Double-Blind, Placebo-Controlled, Multicenter, 6-Month Study of the Efficacy and Safety of Valtrex 1g QD vs. Placebo for the Suppression of HSV-2 Genital Herpes in Newly Diagnosed Immunocompetent Patients

Conditions
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Herpes Genitalis

Intervention / Treatment
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* Drug: Valaciclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: In overall general good health. Females can enter and participate in this study if they are of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or if of childbearing potential, has a negative pregnancy test (urine) at screening and agrees to use GSK stipulated contraceptive methods. Must be newly diagnosed with a first recognized episode of GH at the time of the Screening Visit or within 3 months prior to the Screening Visit. Exclusion criteria: Known or suspected to be immunocompromised (e.g., subjects receiving immunosuppressive therapy or chemotherapy for malignancy, or are seropositive for HIV). Received an investigational drug in the 30 days prior to the study. Receiving systemic antiviral or immunomodulatory treatments. Must not have received systemic antiviral treatments (e.g., valaciclovir, Famvir (famciclovir), acyclovir, lysine) within 3 days of starting study drug or immunomodulatory treatments in the 30 days before starting study drug. Clinically significant impaired renal function as defined by a creatinine clearance <30 ml/min, calculated using the Cockcroft-Gault formula. Clinically significant impaired hepatic function defined as an ALT (alanine transaminase) level > 5 times the normal upper limit. Subjects with active liver disease. Known to be hypersensitive to acyclovir, famciclovir, ganciclovir or any component of valaciclovir formulations. Known resistance to acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir or valganciclovir. Subjects with malabsorption or vomiting syndrome or other gastrointestinal dysfunction that might impair drug pharmacokinetics. Women contemplating pregnancy within the duration of the study drug dosing period. Women who are pregnant and/or nursing mothers Current history of alcohol or drug abuse. Received suppressive (daily) therapy for genital herpes prior to enrollment.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valaciclovir<br>Participants received double blinded treatment of oral dose of Valacyclovir 1 g given as 2 x 500 mg caplets QD for 6 months (24 weeks). | Drug: Valaciclovir<br>* 1g once daily<br>|
| Placebo Comparator: Placebo<br>Participants received double blinded treatment of oral dose of matching placebo to Valacyclovir 1 gram (g) given as 2 x 500 milligram (mg) caplets once daily (QD) for 6 months (24 weeks). | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Time to First GH Recurrence | Diary cards were issued to the participants during randomization visit for recording GH recurrences. HSV recurrences since the last visit was assessed after review of the diary card and discussion with the participant. The percentage of participants with time to first GH recurrence was based on Kaplan-Meier estimates. Confidence intervals for differences in proportions was calculated using the standard error for the Kaplan-Meier estimate derived using Greenwood's formula. | Day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of GH Recurrences Per Month Within the 6-month Study Period | Mean number of GH recurrence reaching macular/papular stage per month was reported. Diary cards were issued to the participants during randomization visit for the recording GH recurrences. HSV recurrences since the last visit was assessed after review of the diary card and discussion with the participant. | Up to Day 168 | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as any untoward medical occurrence that, at any dose results in death, was life-threatening, required hospitalization or prolongation of hospitalization, results in disability/incapacity, was a congenital anomaly/birth defect or medically significant. | Upto Day 168 | 
| Percentage of Participants With Time to First Oral Herpes Simplex Virus (HSV) Outbreak Within 6-months | Diary cards were issued to the participants during randomization visit for recording HSV outbreak within 6-momths. HSV outbreak was assessed after review of the diary card and discussion with the participant. The percentage of participants who had first oral HSV outbreak at 6-months was reported. | Day 168 | 
| Number of Isolates With Resistance to Acyclovir (ACV) | Culture samples were tested for AVC-susceptibility by the analytical laboratory. Re-testing of the ACV resistant isolates was carried out to check if the half maximal inhibitory concentration (IC-50s) for all the ACV resistant isolates were within the expected errors of 2.0 microgram per milliliters (mcg/ml) cut-off for the plaque reduction assay. Those isolates that confirm to be resistant in repeat assays were considered as resistant to ACV. | Day 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VALTREX®, valaciclovir, genital herpes, HSV-2, suppression