VALTREX(Valacyclovir) Once Daily for Viral Shedding In Su... | NCT00306293

Name	Type	Description	Arm Group Labels	Other Names
valacyclovir	Drug	valacyclovir

Measure	Description	Time Frame
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)	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.	Up to 60 days in each treatment period (Up to 148 days)

Measure	Description	Time Frame
Mean Percent Days Subclinical Shedding (no Genital Lesions Present)	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.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Anaheim	California	92805	United States
GSK Investigational Site

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

ID	Type	URL	Comment
VLX105832	Statistical Analysis Plan	View IPD

ID	Title	Description
FG000	VALTREX 1 g First Then Placebo	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.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

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.

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.

Posted

Mean

Standard Deviation

Percent of days

Up to 60 days in each treatment period (Up to 148 days)

ID	Title	Description
OG000	VALTREX 1 g, OD	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.
OG001	Placebo	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.

Units	Counts
Participants	OG00052 OG00152

Title

Denominators

Categories

Title	Measurements
	OG0002.9± 5.6 OG00113.5± 16.9

Secondary

Mean Percent Days Subclinical Shedding (no Genital Lesions Present)

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.

Intent-to-Treat Crossover

Posted

Mean

Standard Deviation

Percentage of days

Up to 60 days in each treatment period (Up to 148 days)

ID	Title	Description
OG000	VALTREX 1 g, OD	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.
OG001	Placebo	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.

Secondary

Mean Percent Days Clinical Shedding (Presence of Genital Lesions)

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.

Intent-to-Treat Crossover

Posted

Mean

Standard Deviation

Percentage of Days

Up to 60 days in each treatment period (Up to 148 days)

ID	Title	Description
OG000	VALTREX 1 g, OD	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.
OG001	Placebo	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.

Secondary

Percentage of Participants With no Shedding

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.

Intent-to-Treat Crossover

Posted

Number

Percentage of participants

Up to 60 days in each treatment period (Up to 148 days)

ID	Title	Description
OG000	VALTREX 1 g, OD	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.
OG001	Placebo	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.

Secondary

Percentage of Participants With at Least One Genital Herpes Recurrence

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.

Intent-to-Treat Crossover

Posted

Number

Percetage of participants

Up to 60 days in each treatment period (Up to 148 days)

ID	Title	Description
OG000	VALTREX 1 g, OD	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.
OG001	Placebo	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.

Units	Counts
Participants

Secondary

Median Time to First Genital Herpes Recurrence (Days)

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.

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.

Posted

Median

Full Range

Days

Up to Day 68

ID	Title	Description
OG000	VALTREX 1 g First Then Placebo	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.
OG001	Placebo First Then VALTREX 1 g	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.

Units	Counts

Secondary

Number of Participants With Any Adverse Event (AE) and Serious Adverse Event (SAE)

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.

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

Posted

Count of Participants

Participants

Up to 148 days

ID	Title	Description
OG000	VALTREX 1 g, OD	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.
OG001	Placebo	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.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fungal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected62 at risk EG0016 affected62 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected62 at risk EG0011 affected62 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected62 at risk EG0011 affected62 at risk
Vaginitis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected62 at risk EG0011 affected62 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected62 at risk EG0010 affected62 at risk
Ear infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected62 at risk EG0010 affected62 at risk
Folliculitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0011 affected62 at risk
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0011 affected62 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected62 at risk EG0010 affected62 at risk
Vulvovaginitis trichomonal	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0012 affected62 at risk
Anogenital warts	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Cervicitis human papilloma virus	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Hordeolum	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Labyrinthitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Onychomycosis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Pelvic inflammatory disease	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Sialoadenitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0012 affected62 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Tendon injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0012 affected62 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Dental caries	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0012 affected62 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0012 affected62 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0012 affected62 at risk
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0011 affected62 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected62 at risk EG0010 affected62 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Blood pressure increased	Investigations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Smear cervix abnormal	Investigations	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0012 affected62 at risk
Sleep disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Stress	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Pollakiuria	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Urinary tract disorder	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Vulvovaginal discomfort	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Vulvovaginal dryness	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0001 affected62 at risk EG0010 affected62 at risk
Abnormal sensation in eye	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected62 at risk EG0011 affected62 at risk

ID	Term
D006560	Herpes Labialis
D006558	Herpes Genitalis

ID	Term
D006561	Herpes Simplex
D006566	Herpesviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections
D017193	Skin Diseases, Viral
D008047	Lip Diseases
D009059	Mouth Diseases
D009057	Stomatognathic Diseases
D012874	Skin Diseases, Infectious
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D003141	Communicable Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases
D005832	Genital Diseases, Male
D052801	Male Urogenital Diseases

ID	Term
D000212	Acyclovir
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	VALTREX 1 g, OD	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.	0	62	0	62	19	62
EG001	Placebo	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.	0	62	0	62	26	62