Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01448616
• Collaborator: CONRAD (Other), Gilead Sciences (Industry)
• Enrollment: 73
• Location: 1
• Arms: 4
• Duration (Months): 40
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The investigators propose a randomized, double blind, placebo-controlled, cross-over trial to evaluate the effect of oral and topical (vaginal gel) tenofovir on genital herpes simplex virus (HSV) shedding among herpes simplex virus type-2 (HSV-2) seropositive, human immunodeficiency virus (HIV) seronegative women. The investigators hypothesize that tenofovir will reduce genital HSV shedding compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Herpes Simplex Type II	Drug: TDF; Drug: Placebo Vaginal Gel; Drug: Vaginal TFV Gel; Drug: Placebo Tablets	Phase 4

Detailed Description

The investigators propose a randomized, double-blind, placebo-controlled, cross-over study of 55 adult, healthy women who are HSV-2 seropositive and HIV-1 seronegative. Women will first participate in a run-in phase with twice daily swabbing. Following 4 weeks of swabbing, participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drug will be administered daily.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Tenofovir on Genital HSV Shedding: a Randomized, Double-blind, Placebo-controlled Clinical Trial
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Run-in Phase Women will first participate in a run-in phase with twice daily swabbing.
Experimental: Study Drug Phase: TDF Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.	Drug: TDF; Oral tenofovir will be administered as tablets. TDF (Viread®) tablets contain 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.; Other Names: Tenofovir disoproxil fumarate (TDF) oral tablets ; Drug: Placebo Vaginal Gel; Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible. The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects - negative or positive - on study endpoints.; Other Names: Placebo gel
Experimental: Study Drug Phase: Vaginal TFV Gel Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.	Drug: Vaginal TFV Gel; Tenofovir 1% gel (w/w) is a gel formulation of tenofovir. Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible.; Other Names: Tenofovir 1% Vaginal Gel ; Drug: Placebo Tablets; TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.; Other Names: Oral placebo
Placebo Comparator: Study Drug Phase: Double Placebo Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.	Drug: Placebo Vaginal Gel; Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible. The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects - negative or positive - on study endpoints.; Other Names: Placebo gel ; Drug: Placebo Tablets; TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.; Other Names: Oral placebo

Outcome Measures

Primary Outcome Measures

1. HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo [Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase]

   The within-person changes in rate of HSV shedding during study drug administration (treatment phase) compared with the rate of HSV shedding during lead-in observation phase in the same participants. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment. This is analyzed separately for each treatment arm and not compared between arms.

Secondary Outcome Measures

1. Within-person Changes in Log-copy Numbers of HSV [Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase]

   The within-person changes in mean log-copy numbers of HSV shed during treatment phase (oral TDF, vaginal TFV, or double placebo) compared with the lead-in (observation) phase in the same participants. Each treatment arm is analyzed separately without comparison between arms. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.

2. Genital Lesion Rate [Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase]

   The within person change in proportion of days with lesions between the lead-in (observational) and study drug (treatment) phase for each arm separately. No between arm comparisons were performed. We include intent to treat with all randomized participants as well as per protocol (persons receiving study drug for at least 30 days with 90% or better reported compliance per returned product counts). We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.

3. Asymptomatic Shedding (Shedding on Days Without Genital Lesions) [Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase]

   Within person changes in shedding on days without lesions between the lead-in (observational) phase and the study drug (treatment) phase. Each arm is evaluated separately and no inter arm comparisons are made. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women age 18-50

• HSV-2 seropositive by the University of Washington (UW) Western blot

• History of recurrent genital herpes, with more than 4 recurrences but less than 10 in the last year or, if currently on suppressive therapy, with more than 4 recurrences but less than 10 in the year prior to starting suppressive therapy

• HIV negative

• General good health

• Willing to not use antiviral therapy (other than the study drug) for the duration of the study

• Willing to obtain a swab from genital secretions twice daily for the duration of the study

• Willing to use effective birth control

• Able to provide written informed consent at screening and enrollment

Exclusion Criteria:

• HIV positive or at high risk for HIV acquisition (intravenous drug user or HIV+ sex partner)

• Hepatitis B (HepB) antigen (Ag) positive, or at high risk for HepB acquisition and not vaccinated

• Have a history of adverse reaction to tenofovir and/or adefovir

• Immunosuppressive medications, except for intranasal or topical (not high potency) steroids.

• Any kidney disease, or renal insufficiency, defined as serum creatinine >1.5 mg/dl. Participants with a prior history of a single episode of pyelonephritis will be eligible.

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times upper limit of normal

• Pregnancy, as confirmed by a urine pregnancy test, planning to become pregnant during the course of the trial, or breast-feeding.

• Serious medical conditions or active infections

• Any other conditions that in the judgment of the investigator would preclude successful completion of the clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Washington Virology Research Clinic	Seattle	Washington	United States	98104

Sponsors and Collaborators

• University of Washington
• CONRAD
• Gilead Sciences

Investigators

• Principal Investigator: Anna Wald, MD, MPH, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anna Wald, Professor, University of Washington
• ClinicalTrials.gov Identifier: NCT01448616
• Other Study ID Numbers: 41250-J
• First Posted: Oct 7, 2011
• Last Update Posted: Jan 12, 2016
• Last Verified: Dec 1, 2015

• Additional relevant MeSH terms: Herpes Simplex; Tenofovir

Study Results

Participant Flow

Arm/Group Title	Observational Group	Oral TDF + Vaginal Placebo Gel	Oral Placebo + Vaginal Tenofovir 1% Gel	Placebo Oral + Placebo Vaginal Gel
Arm/Group Description	All enrolled participants completed 28 days of twice-daily genital swabbing for HSV DNA. Only women completing >90% of requested swabs were randomized.	Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application	Participants received a matching oral placebo to study product and 40mg of TFV gel both to be used daily	This group received the matching placebos to both study products
Period Title: Lead-In (Observational Phase)
STARTED	73	0	0	0
COMPLETED	64	0	0	0
NOT COMPLETED	9	0	0	0
Period Title: Lead-In (Observational Phase)
STARTED	0	24	27	13
COMPLETED	0	22	23	9
NOT COMPLETED	0	2	4	4

Baseline Characteristics

Arm/Group Title	Oral TDF + Vaginal Placebo Gel	Oral Placebo + Vaginal TFV Gel	Oral Placebo + Vaginal Placebo Gel	Total
Arm/Group Description	Participants randomized to receive 300mg Tenofovir Disaproxil Fumarate (TDF) 1 tab daily + the universal placebo vaginal gel (4ml) to be used daily.	Participants randomized to receive matching oral placebo tab once daily + tenofovir (TFV) 1% vaginal gel (40mg in 4ml) to be used daily	Participants received matching oral tab and placebo gel both to be used daily	Total of all reporting groups
Overall Participants	24	27	13	64
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	24 100%	27 100%	13 100%	64 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	39.1	36.7	41.0	37.3
Sex: Female, Male (Count of Participants)
Female	24 100%	27 100%	13 100%	64 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	24 100%	27 100%	13 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo
Description	The within-person changes in rate of HSV shedding during study drug administration (treatment phase) compared with the rate of HSV shedding during lead-in observation phase in the same participants. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment. This is analyzed separately for each treatment arm and not compared between arms.
Time Frame	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Outcome Measure Data

Analysis Population Description

This includes intent to treat, ( all randomized participants) and per-protocol analyses (persons receiving 30 or more days of treatment with >90% compliance as recorded by returned product counts)

Arm/Group Title	Oral TDF + Vaginal Placebo Gel	Oral Placebo + Vaginal TFV Gel	Oral Placebo + Vaginal Placebo
Arm/Group Description	tenofovir disoproxil fumarate (TDF): Oral tenofovir will be administered as tablets. TDF (Viread®) tablets contain 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals. placebo gel: Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible. The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects - negative or positive - on study endpoints.	Tenofovir: Tenofovir 1% gel (w/w) is a gel formulation of tenofovir. Study participants are instructed to insert one dose (the entire contents of one applicator 40mg/4ml) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible. placebo tablets: TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.	placebo tablets: TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals. placebo gel: Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible. The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects - negative or positive - on study endpoints.
Measure Participants	24	27	13
Lead-in Phase	22.9	13.8	21.3
Treatment Phase	19.5	12.0	20.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral TDF + Vaginal Placebo Gel
	Comments	For per protocol analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	For per protocol analysis
	Method	Poisson GLME
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.60 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Placebo + Vaginal TFV Gel
	Comments	This is the per-protocol analysis including only persons who completed >30 days of study drug with 90% or better compliance by returned product count
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments	For per protocol analysis
	Method	Poisson GLME
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Placebo + Vaginal Placebo
	Comments	This is the per-protocol analysis including only persons who completed >30 days of study drug with 90% or better compliance by returned product count
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Poisson GLME
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Within-person Changes in Log-copy Numbers of HSV
Description	The within-person changes in mean log-copy numbers of HSV shed during treatment phase (oral TDF, vaginal TFV, or double placebo) compared with the lead-in (observation) phase in the same participants. Each treatment arm is analyzed separately without comparison between arms. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.
Time Frame	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Outcome Measure Data

Analysis Population Description

Analysis is within person changes such that the observational group contributed to analyses of those persons in each treatment randomization group

Arm/Group Title	Oral TDF + Vaginal Placebo Gel	Oral Placebo + Vaginal Tenofovir 1% Gel	Placebo Oral + Placebo Vaginal Gel
Arm/Group Description	Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application	Participants received a matching oral placebo to study product and 40mg of TFV gel both to be used daily	This group received the matching placebos to both study products
Measure Participants	24	27	13
Lead-in Phase	4.02	4.47	3.71
Treatment Phase	4.11	4.40	4.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral TDF + Vaginal Placebo Gel
	Comments	For per protocol analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Linear Mixed Effects Model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Placebo + Vaginal TFV Gel
	Comments	For per protocol analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Linear Mixed Effects Model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Placebo + Vaginal Placebo
	Comments	for Per protocol only
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Linear Mixed Effects Model
	Comments

3. Secondary Outcome

Title	Genital Lesion Rate
Description	The within person change in proportion of days with lesions between the lead-in (observational) and study drug (treatment) phase for each arm separately. No between arm comparisons were performed. We include intent to treat with all randomized participants as well as per protocol (persons receiving study drug for at least 30 days with 90% or better reported compliance per returned product counts). We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.
Time Frame	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral TDF + Vaginal Placebo Gel	Oral Placebo + Vaginal Tenofovir 1% Gel	Placebo Oral + Placebo Vaginal Gel
Arm/Group Description	Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application	Participants received a matching oral placebo to study product and 40mg/4ml of TFV gel both to be used daily	This group received the matching placebos to both study products
Measure Participants	24	27	13
Lead-in Phase	11.8	8.7	13.6
Treatment Phase	11.6	7.1	14.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral TDF + Vaginal Placebo Gel
	Comments	Per protocol analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	Poisson GLME
	Comments

4. Secondary Outcome

Title	Asymptomatic Shedding (Shedding on Days Without Genital Lesions)
Description	Within person changes in shedding on days without lesions between the lead-in (observational) phase and the study drug (treatment) phase. Each arm is evaluated separately and no inter arm comparisons are made. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.
Time Frame	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Outcome Measure Data

Analysis Population Description

All randomized participants are included in ITT analysis. Per protocol analysis includes persons receiving 30 or more days of study drug with >90% adherence as documented by returned product counts.

Arm/Group Title	Oral TDF + Vaginal Placebo Gel	Oral Placebo + Vaginal Tenofovir 1% Gel	Placebo Oral + Placebo Vaginal Gel
Arm/Group Description	Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application	Participants received a matching oral placebo to study product and 40mg of TFV gel both to be used daily	This group received the matching placebos to both study products
Measure Participants	24	27	13
Lead-in Phase	17.5	7.6	14.4
Treatment Phase	13.7	8.2	12.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral TDF + Vaginal Placebo Gel
	Comments	per protocol only here
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	Poisson GLME
	Comments

Adverse Events

Time Frame	Adverse Events were collected during the course of the lead-in phase (4 weeks) and the treatment (study drug) phase (5 weeks) and final AEs were recorded at a post-treatment follow up telephone visit 2 weeks after completing the study products.
Adverse Event Reporting Description	Unscheduled study visits were conducted as needed to evaluate potential adverse events. Adverse events were systematically collected in daily participant diaries and queried at each biweekly study visit.
Arm/Group Title	Observational Group		Oral TDF + Vaginal Placebo Gel		Oral Placebo + Vaginal Tenofovir 1% Gel		Placebo Oral + Placebo Vaginal Gel
Arm/Group Description	All enrolled participants completed 28 days of twice-daily genital swabbing for HSV DNA. Only women completing >90% of requested swabs were randomized.		Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application		Participants received a matching oral placebo to study product and 40mg of TFV gel both to be used daily		This group received the matching placebos to both study products
All Cause Mortality
	Observational Group		Oral TDF + Vaginal Placebo Gel		Oral Placebo + Vaginal Tenofovir 1% Gel		Placebo Oral + Placebo Vaginal Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Observational Group		Oral TDF + Vaginal Placebo Gel		Oral Placebo + Vaginal Tenofovir 1% Gel		Placebo Oral + Placebo Vaginal Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		0/24 (0%)		0/27 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Observational Group		Oral TDF + Vaginal Placebo Gel		Oral Placebo + Vaginal Tenofovir 1% Gel		Placebo Oral + Placebo Vaginal Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/73 (15.1%)		12/24 (50%)		11/27 (40.7%)		3/13 (23.1%)
Gastrointestinal disorders
Diarrhea	0/73 (0%)		5/24 (20.8%)		0/27 (0%)		0/13 (0%)
Nausea	0/73 (0%)		3/24 (12.5%)		0/27 (0%)		0/13 (0%)
Abdominal Pain	0/73 (0%)		3/24 (12.5%)		0/27 (0%)		0/13 (0%)
Infections and infestations
Candida Intertrigo	0/73 (0%)		0/24 (0%)		0/27 (0%)		1/13 (7.7%)
Nervous system disorders
Headache	0/73 (0%)		3/24 (12.5%)		4/27 (14.8%)		0/13 (0%)
Reproductive system and breast disorders
Vulvovaginitis	2/73 (2.7%)		1/24 (4.2%)		2/27 (7.4%)		1/13 (7.7%)
Vulvovaginal pruritis	1/73 (1.4%)		1/24 (4.2%)		1/27 (3.7%)		2/13 (15.4%)
Vulvovaginal burning	0/73 (0%)		0/24 (0%)		2/27 (7.4%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Viral Illness	8/73 (11%)		4/24 (16.7%)		2/27 (7.4%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Skin Irritation	0/73 (0%)		0/24 (0%)		0/27 (0%)		1/13 (7.7%)

Limitations/Caveats

The study was not powered to detect differences in lesion rate; the study was appropriately powered to detect a 50% decrease in viral shedding only, and therefore may have been underpowered to detect significant findings for secondary outcomes.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.