VALTREX(Valacyclovir) Once Daily for Viral Shedding In Subjects Newly Diagnosed With HSV-2

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00306293
• Collaborator: (none)
• Enrollment: 70
• Locations: 18
• Actual Duration (Months): 9.2
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Eligible subjects will be randomized to receive VALTREX 1g or placebo once daily for 60 days in a two-way crossover study with a washout period of 7 days in between.

Condition or Disease	Intervention/Treatment	Phase
Herpes Labialis	Drug: valacyclovir	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Valacyclovir 1g Once Daily on HSV-2 Viral Shedding in Subjects Newly Diagnosed With Genital Herpes Infection
• Actual Study Start Date: Feb 20, 2006
• Actual Primary Completion Date: Nov 27, 2006
• Actual Study Completion Date: Nov 27, 2006

Outcome Measures

Primary Outcome Measures

1. Mean Percent Days of Total Shedding (Clinical and Subclinical) as Determined by Type-specific Polymerase Chain Reaction (PCR) Assay for Herpes Simplex Virus Type 2 (HSV-2) [Up to 60 days in each treatment period (Up to 148 days)]

   Each participant's study day were classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab are positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Percent of days with HSV-2 shedding was defined for each participant as the percent of days with PCR data for which HSV-2 shedding was detected by a positive PCR result, i.e., the number of days with HSV-2 PCR shedding divided by total number of days with PCR data, multiplied by 100. Sum of the percent clinical and nonclinical shedding days was reported as total shedding. Mean percent of days with HSV-2 shedding was reported for each treatment group.

Secondary Outcome Measures

1. Mean Percent Days Subclinical Shedding (no Genital Lesions Present) [Up to 60 days in each treatment period (Up to 148 days)]

   The percent of days with subclinical HSV-2 shedding was defined as the percent of all days with PCR data for which subclinical HSV-2 shedding was detected (shedding in the absence of a genital lesion). Mean percent of days with subclinical HSV-2 shedding was reported for each treatment group. Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits.

2. Mean Percent Days Clinical Shedding (Presence of Genital Lesions) [Up to 60 days in each treatment period (Up to 148 days)]

   The percent of days with clinical HSV-2 shedding was defined as the percent of all days with PCR data for which clinical HSV-2 shedding was detected (shedding in the presence of a genital lesion). Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Mean percent of days with clinical HSV-2 shedding was reported for each treatment group.

3. Percentage of Participants With no Shedding [Up to 60 days in each treatment period (Up to 148 days)]

   The proportion of participants with no shedding was defined as the number of participants with no HSV-2 shedding detected by PCR divided by the total number of participants with PCR data in the Treatment Period. Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Mean percent of days with no shedding was reported for each treatment group.

4. Percentage of Participants With at Least One Genital Herpes Recurrence [Up to 60 days in each treatment period (Up to 148 days)]

   The proportion of participants with at least one genital herpes recurrence was defined as the number of participants with at least one investigator-confirmed genital herpes recurrence divided by the total number of participants with at least one clinic visit in the treatment period.

5. Median Time to First Genital Herpes Recurrence (Days) [Up to Day 68]

   Time to first genital herpes recurrence was evaluated using Kaplan-Meier estimates of investigator-confirmed genital herpes recurrences censoring the data from participants who prematurely discontinue the study at the time of discontinuation.

6. Number of Participants With Any Adverse Event (AE) and Serious Adverse Event (SAE) [Up to 148 days]

   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. SAE include adverse events that result in death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. No SAEs were reported in this study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is in overall general good health.

• If female, subject must be of:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal or surgically sterile); or

2. Childbearing potential, but must have a negative pregnancy test at randomization, and must be compliant with one of the following: Complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period of 1 week after study completion or premature discontinuation from the study (to account for elimination of the drug); Have a male partner who is confirmed to be sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; Use of contraceptive(s) with a documented failure rate of less than 1% per year, including but not limited to: implants of levonorgestrel, use of injectable progestogen, oral contraceptives (either combined or progestogen only), an intrauterine device (IUD) or spermicide plus a mechanical barrier (condom/diaphragm).

• Subjects must be newly diagnosed with a first recognized episode of genital herpes as described in (a) or (b) below (See Appendix 3): a.HSV-2 seropositive at screen, with documented clinical signs and symptoms consistent with genital herpes at screen or within 4 months prior to randomization or b.HSV-2 seronegative at screen, AND HSV-2 culture positive or HSV-2 PCR positive with documented clinical signs and symptoms consistent with genital herpes at screen or within 4 months prior to randomization.

• Subject must be willing and able to provide written informed consent and comply with the protocol.

Exclusion Criteria:

• Subject is known or suspected to be immunocompromised (e.g., subjects receiving immunosuppressive therapy or chemotherapy for malignancy, or are seropositive for HIV).

• Subject received an investigational drug in the 30 days prior to the randomization visit.

• Subject is receiving systemic antiviral or immunomodulatory treatments.

• Subjects who have received systemic antiherpetic treatments (e.g., valacyclovir, acyclovir, ganciclovir, famciclovir) within 3 days of starting study drug, or immunomodulatory treatments in the 30 days before starting study drug.

• Subject has clinically significantly impaired renal function as defined by creatinine clearance less than 50ml/min (calculated using the Cockcroft-Gault formula).

• Subjects with a history or evidence of decompensated liver disease, or clinically significantly impaired hepatic function defined as an ALT (alanine transaminase) level

3 times the normal upper limit.

• Subject is known to be hypersensitive to valacyclovir, acyclovir, ganciclovir or famciclovir.

• Subject has malabsorption or vomiting syndrome or other gastrointestinal dysfunction that may impair drug pharmacokinetics.

• Female subject who is contemplating pregnancy within the duration of the study drug dosing period.

• Female subject who is pregnant and/or nursing.

• Subject with current alcohol or drug abuse.

• Subjects who have received suppressive (daily) therapy for genital herpes prior to randomization. Suppressive therapy is defined as daily antiherpetic therapy of at least 4 weeks duration.

• Subjects with a history of ocular HSV (herpes simplex virus) infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Anaheim	California	United States	92805
2	GSK Investigational Site	Carmichael	California	United States	95608
3	GSK Investigational Site	Fair Oaks	California	United States	95628
4	GSK Investigational Site	Sacramento	California	United States	95816
5	GSK Investigational Site	San Diego	California	United States	92123
6	GSK Investigational Site	Boynton Beach	Florida	United States	33437
7	GSK Investigational Site	Saint Petersburg	Florida	United States	33710
8	GSK Investigational Site	Indianapolis	Indiana	United States	46202
9	GSK Investigational Site	South Bend	Indiana	United States	46601
10	GSK Investigational Site	Portage	Michigan	United States	49024
11	GSK Investigational Site	New York	New York	United States	10029
12	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599
13	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
14	GSK Investigational Site	Tulsa	Oklahoma	United States	74104
15	GSK Investigational Site	Portland	Oregon	United States	97210
16	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19140
17	GSK Investigational Site	Memphis	Tennessee	United States	38104
18	GSK Investigational Site	Memphis	Tennessee	United States	38120

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00306293
• Other Study ID Numbers: VLX105832
• First Posted: Mar 23, 2006
• Last Update Posted: Mar 23, 2018
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Recurrent Genital Herpes
• Additional relevant MeSH terms: Herpes Simplex; Herpes Labialis; Valacyclovir

Study Results

Participant Flow

Recruitment Details	Seventy participants were enrolled at 14 centers in the United States. The study was conducted between 20 February 2006 and 28 November 2006.
Pre-assignment Detail	Out of the 70 participants 35 participants were randomized to the VALTREX 1 g First then Placebo treatment sequence (VAL-PBO) and 35 participants were randomized to the Placebo first then VALTREX 1 g treatment sequence (PBO-VAL).

Arm/Group Title	VALTREX 1 g First Then Placebo	Placebo First Then VALTREX 1 g
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in first period followed by matching placebo 2 caplets, OD, orally, for 60 days in period second period. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in first period followed by VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in second period. The two treatment periods were separated by washout period of seven days.
Period Title: Period 1 (Day 1 to Day 60)
STARTED	35	35
COMPLETED	27	27
NOT COMPLETED	8	8
Period Title: Period 1 (Day 1 to Day 60)
STARTED	27	27
COMPLETED	27	27
NOT COMPLETED	0	0
Period Title: Period 1 (Day 1 to Day 60)
STARTED	27	27
COMPLETED	24	26
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets) and matching placebo 2 caplets, orally, OD, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Overall Participants	70
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	30.9 (9.64)
Sex: Female, Male (Count of Participants)
Female	49 70%
Male	21 30%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	28 40%
American Indian or Alaska Native	2 2.9%
Asian - East Asian Heritage	2 2.9%
White - Arabic/North African Heritage	1 1.4%
White - White/Caucasian/European Heritage	36 51.4%
Mixed Race	1 1.4%

Outcome Measures

1. Primary Outcome

Title	Mean Percent Days of Total Shedding (Clinical and Subclinical) as Determined by Type-specific Polymerase Chain Reaction (PCR) Assay for Herpes Simplex Virus Type 2 (HSV-2)
Description	Each participant's study day were classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab are positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Percent of days with HSV-2 shedding was defined for each participant as the percent of days with PCR data for which HSV-2 shedding was detected by a positive PCR result, i.e., the number of days with HSV-2 PCR shedding divided by total number of days with PCR data, multiplied by 100. Sum of the percent clinical and nonclinical shedding days was reported as total shedding. Mean percent of days with HSV-2 shedding was reported for each treatment group.
Time Frame	Up to 60 days in each treatment period (Up to 148 days)

Outcome Measure Data

Analysis Population Description

Intent to Treat Crossover population comprised of all participants in the Intent to Treat population who had at least one PCR swabbing result in each Treatment Period. Intent to Treat population comprised of all participants who received at least one dose of investigational product.

Arm/Group Title	VALTREX 1 g, OD	Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Measure Participants	52	52
Mean (Standard Deviation) [Percent of days]	2.9 (5.6)	13.5 (16.9)

2. Secondary Outcome

Title	Mean Percent Days Subclinical Shedding (no Genital Lesions Present)
Description	The percent of days with subclinical HSV-2 shedding was defined as the percent of all days with PCR data for which subclinical HSV-2 shedding was detected (shedding in the absence of a genital lesion). Mean percent of days with subclinical HSV-2 shedding was reported for each treatment group. Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits.
Time Frame	Up to 60 days in each treatment period (Up to 148 days)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Crossover

Arm/Group Title	VALTREX 1 g, OD	Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Measure Participants	52	52
Mean (Standard Deviation) [Percentage of days]	2.4 (4.8)	11 (15.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VALTREX 1 g, OD, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments
Method of Estimation	Estimation Parameter	Percent change from Placebo
	Estimated Value	-78
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percent change in days with Subclinical HSV-2 Viral Shedding after VALTREX 1g treatment from the placebo

3. Secondary Outcome

Title	Mean Percent Days Clinical Shedding (Presence of Genital Lesions)
Description	The percent of days with clinical HSV-2 shedding was defined as the percent of all days with PCR data for which clinical HSV-2 shedding was detected (shedding in the presence of a genital lesion). Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Mean percent of days with clinical HSV-2 shedding was reported for each treatment group.
Time Frame	Up to 60 days in each treatment period (Up to 148 days)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Crossover

Arm/Group Title	VALTREX 1 g, OD	Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Measure Participants	52	52
Mean (Standard Deviation) [Percentage of Days]	0.6 (1.7)	2.4 (4.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VALTREX 1 g, OD, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Wilcoxon Rank Sum
	Comments
Method of Estimation	Estimation Parameter	Percent change from Baseline
	Estimated Value	-77
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percent change in 'percentage of days with clinical HSV-2 viral shedding', after VALTREX 1g treatment from the placebo

4. Secondary Outcome

Title	Percentage of Participants With no Shedding
Description	The proportion of participants with no shedding was defined as the number of participants with no HSV-2 shedding detected by PCR divided by the total number of participants with PCR data in the Treatment Period. Each participant's study day was classified as either 'shedding' (positive HSV-2 result), 'no shedding' (negative HSV-2 result), or 'unknown' (swabbing not done or assay result not available) confirmed by PCR. If either the daily genital swab or a lesion swab was positive, the day was classified as 'shedding'. Study shedding day was classified as either 'clinical' (investigator-confirmed presence of genital lesions) or 'subclinical' (no genital lesions) by the investigator during recurrence visits. Mean percent of days with no shedding was reported for each treatment group.
Time Frame	Up to 60 days in each treatment period (Up to 148 days)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Crossover

Arm/Group Title	VALTREX 1 g, OD	Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Measure Participants	52	52
Number [Percentage of participants]	60 85.7%	29 NaN

5. Secondary Outcome

Title	Percentage of Participants With at Least One Genital Herpes Recurrence
Description	The proportion of participants with at least one genital herpes recurrence was defined as the number of participants with at least one investigator-confirmed genital herpes recurrence divided by the total number of participants with at least one clinic visit in the treatment period.
Time Frame	Up to 60 days in each treatment period (Up to 148 days)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Crossover

Arm/Group Title	VALTREX 1 g, OD	Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Measure Participants	52	52
Number [Percetage of participants]	21 30%	48 NaN

6. Secondary Outcome

Title	Median Time to First Genital Herpes Recurrence (Days)
Description	Time to first genital herpes recurrence was evaluated using Kaplan-Meier estimates of investigator-confirmed genital herpes recurrences censoring the data from participants who prematurely discontinue the study at the time of discontinuation.
Time Frame	Up to Day 68

Outcome Measure Data

Analysis Population Description

First Period Efficacy Population included participants in the Intent to Treat Exposed Population and was used for efficacy analyses restricted to the First Treatment Period.

Arm/Group Title	VALTREX 1 g First Then Placebo	Placebo First Then VALTREX 1 g
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in first period followed by matching placebo 2 caplets, OD, orally, for 60 days in period second period. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in first period followed by VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in second period. The two treatment periods were separated by washout period of seven days.
Measure Participants	33	35
Median (Full Range) [Days]	NA	61

7. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious Adverse Event (SAE)
Description	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. SAE include adverse events that result in death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. No SAEs were reported in this study.
Time Frame	Up to 148 days

Outcome Measure Data

Analysis Population Description

Intent to treat exposed population comprised of all participants who received at least one dose of investigational product.

Arm/Group Title	VALTREX 1 g, OD	Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.	Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
Measure Participants	62	62
Any AE	19 27.1%	26 NaN
Any SAE	0 0%	0 NaN

Adverse Events

Time Frame	AE and SAE were collected from randomization visit (Day 1) until the recurrence visit (Day 148)
Adverse Event Reporting Description	Intent-to-Treat Exposed population was used to collect the AEs and SAEs.
Arm/Group Title	VALTREX 1 g, OD		Placebo
Arm/Group Description	Participants received VALTREX 1 g (2 x500 mg caplets), OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.		Participants received matching placebo 2 caplets, OD, orally, for 60 days in a two-way crossover design either in sequence VAL-PBO or PBO-VAL. The two treatment periods were separated by washout period of seven days.
All Cause Mortality
	VALTREX 1 g, OD		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)
Serious Adverse Events
	VALTREX 1 g, OD		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	VALTREX 1 g, OD		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/62 (30.6%)		26/62 (41.9%)
Eye disorders
Abnormal sensation in eye	0/62 (0%)		1/62 (1.6%)
Gastrointestinal disorders
Diarrhoea	1/62 (1.6%)		2/62 (3.2%)
Abdominal pain	0/62 (0%)		1/62 (1.6%)
Dental caries	0/62 (0%)		1/62 (1.6%)
Paraesthesia oral	0/62 (0%)		1/62 (1.6%)
Toothache	0/62 (0%)		1/62 (1.6%)
Infections and infestations
Fungal infection	3/62 (4.8%)		6/62 (9.7%)
Upper respiratory tract infection	3/62 (4.8%)		1/62 (1.6%)
Sinusitis	2/62 (3.2%)		1/62 (1.6%)
Vaginitis bacterial	2/62 (3.2%)		1/62 (1.6%)
Bronchitis	2/62 (3.2%)		0/62 (0%)
Ear infection	2/62 (3.2%)		0/62 (0%)
Folliculitis	1/62 (1.6%)		1/62 (1.6%)
Urinary tract infection	1/62 (1.6%)		1/62 (1.6%)
Vulvovaginal mycotic infection	2/62 (3.2%)		0/62 (0%)
Vulvovaginitis trichomonal	0/62 (0%)		2/62 (3.2%)
Anogenital warts	0/62 (0%)		1/62 (1.6%)
Cervicitis human papilloma virus	0/62 (0%)		1/62 (1.6%)
Hordeolum	0/62 (0%)		1/62 (1.6%)
Labyrinthitis	1/62 (1.6%)		0/62 (0%)
Onychomycosis	1/62 (1.6%)		0/62 (0%)
Pelvic inflammatory disease	0/62 (0%)		1/62 (1.6%)
Sialoadenitis	0/62 (0%)		1/62 (1.6%)
Injury, poisoning and procedural complications
Contusion	0/62 (0%)		2/62 (3.2%)
Concussion	0/62 (0%)		1/62 (1.6%)
Fall	0/62 (0%)		1/62 (1.6%)
Muscle strain	0/62 (0%)		1/62 (1.6%)
Procedural pain	0/62 (0%)		1/62 (1.6%)
Tendon injury	1/62 (1.6%)		0/62 (0%)
Investigations
Alanine aminotransferase increased	1/62 (1.6%)		0/62 (0%)
Aspartate aminotransferase increased	1/62 (1.6%)		0/62 (0%)
Blood pressure increased	1/62 (1.6%)		0/62 (0%)
Smear cervix abnormal	1/62 (1.6%)		0/62 (0%)
Metabolism and nutrition disorders
Anorexia	0/62 (0%)		1/62 (1.6%)
Hypercholesterolaemia	0/62 (0%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/62 (0%)		2/62 (3.2%)
Pain in extremity	0/62 (0%)		2/62 (3.2%)
Back pain	0/62 (0%)		1/62 (1.6%)
Musculoskeletal pain	0/62 (0%)		1/62 (1.6%)
Neck pain	0/62 (0%)		1/62 (1.6%)
Nervous system disorders
Headache	1/62 (1.6%)		2/62 (3.2%)
Migraine	0/62 (0%)		1/62 (1.6%)
Paraesthesia	0/62 (0%)		1/62 (1.6%)
Psychiatric disorders
Depression	0/62 (0%)		2/62 (3.2%)
Sleep disorder	0/62 (0%)		1/62 (1.6%)
Stress	0/62 (0%)		1/62 (1.6%)
Renal and urinary disorders
Pollakiuria	1/62 (1.6%)		0/62 (0%)
Urinary tract disorder	0/62 (0%)		1/62 (1.6%)
Reproductive system and breast disorders
Vulvovaginal discomfort	0/62 (0%)		1/62 (1.6%)
Vulvovaginal dryness	1/62 (1.6%)		0/62 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	1/62 (1.6%)		1/62 (1.6%)
Sinus congestion	2/62 (3.2%)		0/62 (0%)
Cough	0/62 (0%)		1/62 (1.6%)
Skin and subcutaneous tissue disorders
Rash	0/62 (0%)		1/62 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.