Trial Outcomes & Findings for Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding (NCT NCT01448616)

Last Updated: 2023-02-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

73 participants

Primary outcome timeframe

Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Results posted on

2023-02-16

Participant Flow

Participant milestones

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

Reasons for withdrawal

Reasons for withdrawal
Measure	Observational Group All enrolled participants completed 28 days of twice-daily genital swabbing for HSV DNA. Only women completing \>90% of requested swabs were randomized.	Oral TDF + Vaginal Placebo Gel Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application	Oral Placebo + Vaginal Tenofovir 1% Gel Participants received a matching oral placebo to study product and 40mg of TFV gel both to be used daily	Placebo Oral + Placebo Vaginal Gel This group received the matching placebos to both study products
Lead-In (Observational Phase) Collected no genital swabs	3	0	0	0
Lead-In (Observational Phase) Collected <90% of required swabs	6	0	0	0
Study Drug (Treatment Phase) Adverse Event	0	1	1	0
Study Drug (Treatment Phase) Never initiated study drug	0	0	1	2
Study Drug (Treatment Phase) Withdrawal by Subject	0	1	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral TDF + Vaginal Placebo Gel n=24 Participants Participants randomized to receive 300mg Tenofovir Disaproxil Fumarate (TDF) 1 tab daily + the universal placebo vaginal gel (4ml) to be used daily.	Oral Placebo + Vaginal TFV Gel n=27 Participants Participants randomized to receive matching oral placebo tab once daily + tenofovir (TFV) 1% vaginal gel (40mg in 4ml) to be used daily	Oral Placebo + Vaginal Placebo Gel n=13 Participants Participants received matching oral tab and placebo gel both to be used daily	Total n=64 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	27 Participants n=7 Participants	13 Participants n=5 Participants	64 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	39.1 years n=5 Participants	36.7 years n=7 Participants	41.0 years n=5 Participants	37.3 years n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	27 Participants n=7 Participants	13 Participants n=5 Participants	64 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	24 participants n=5 Participants	27 participants n=7 Participants	13 participants n=5 Participants	64 participants n=4 Participants

PRIMARY outcome

Timeframe: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Population: This is the intent-to-treat population (all randomized participants returning at least 1 swab in each phase of study)

Outcome measures

Outcome measures
Measure	Oral TDF + Vaginal Placebo Gel n=24 Participants 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.	Oral Placebo + Vaginal TFV Gel n=27 Participants 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.	Oral Placebo + Vaginal Placebo n=13 Participants 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.
HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo Lead-in Phase	22.9 percentage of swabs positive (%) Interval 20.6 to 25.2	13.8 percentage of swabs positive (%) Interval 12.1 to 15.7	21.3 percentage of swabs positive (%) Interval 18.4 to 24.5
HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo Treatment Phase	19.5 percentage of swabs positive (%) Interval 17.4 to 21.8	12.0 percentage of swabs positive (%) Interval 10.3 to 13.9	20.4 percentage of swabs positive (%) Interval 17.0 to 24.1

SECONDARY outcome

Timeframe: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

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

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.

Outcome measures

Outcome measures
Measure	Oral TDF + Vaginal Placebo Gel n=24 Participants 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.	Oral Placebo + Vaginal TFV Gel n=27 Participants 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.	Oral Placebo + Vaginal Placebo n=13 Participants 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.
Within-person Changes in Log-copy Numbers of HSV Lead-in Phase	4.02 log-copy number of HSV DNA shed Interval 3.21 to 5.29	4.47 log-copy number of HSV DNA shed Interval 2.92 to 6.24	3.71 log-copy number of HSV DNA shed Interval 2.78 to 5.54
Within-person Changes in Log-copy Numbers of HSV Treatment Phase	4.11 log-copy number of HSV DNA shed Interval 3.23 to 5.39	4.40 log-copy number of HSV DNA shed Interval 3.37 to 5.13	4.22 log-copy number of HSV DNA shed Interval 3.35 to 5.45

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Oral TDF + Vaginal Placebo Gel n=24 Participants 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.	Oral Placebo + Vaginal TFV Gel n=27 Participants 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.	Oral Placebo + Vaginal Placebo n=13 Participants 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.
Genital Lesion Rate Lead-in Phase	11.8 percentage of days with lesions (%) Interval 9.5 to 14.5	8.7 percentage of days with lesions (%) Interval 6.8 to 10.9	13.6 percentage of days with lesions (%) Interval 10.3 to 17.5
Genital Lesion Rate Treatment Phase	11.6 percentage of days with lesions (%) Interval 9.3 to 13.3	7.1 percentage of days with lesions (%) Interval 5.3 to 9.2	14.7 percentage of days with lesions (%) Interval 10.7 to 19.6

SECONDARY outcome

Timeframe: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Oral TDF + Vaginal Placebo Gel n=24 Participants 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.	Oral Placebo + Vaginal TFV Gel n=27 Participants 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.	Oral Placebo + Vaginal Placebo n=13 Participants 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.
Asymptomatic Shedding (Shedding on Days Without Genital Lesions) Lead-in Phase	17.5 % days with asymptomatic shedding Interval 15.4 to 19.9	7.6 % days with asymptomatic shedding Interval 6.2 to 9.1	14.4 % days with asymptomatic shedding Interval 11.7 to 17.4
Asymptomatic Shedding (Shedding on Days Without Genital Lesions) Treatment Phase	13.7 % days with asymptomatic shedding Interval 11.8 to 15.8	8.2 % days with asymptomatic shedding Interval 6.8 to 9.9	12.1 % days with asymptomatic shedding Interval 9.2 to 15.5

Adverse Events

Observational Group

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Oral TDF + Vaginal Placebo Gel

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Oral Placebo + Vaginal Tenofovir 1% Gel

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo Oral + Placebo Vaginal Gel

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Observational Group n=73 participants at risk All enrolled participants completed 28 days of twice-daily genital swabbing for HSV DNA. Only women completing \>90% of requested swabs were randomized.	Oral TDF + Vaginal Placebo Gel n=24 participants at risk Women received daily TDF tablets at 300mg + "universal" placebo gel for daily application	Oral Placebo + Vaginal Tenofovir 1% Gel n=27 participants at risk Participants received a matching oral placebo to study product and 40mg of TFV gel both to be used daily	Placebo Oral + Placebo Vaginal Gel n=13 participants at risk This group received the matching placebos to both study products
Gastrointestinal disorders Diarrhea	0.00% 0/73 • 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. 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.	20.8% 5/24 • 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. 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.	0.00% 0/27 • 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. 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.	0.00% 0/13 • 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. 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.
Nervous system disorders Headache	0.00% 0/73 • 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. 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.	12.5% 3/24 • 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. 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.	14.8% 4/27 • 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. 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.	0.00% 0/13 • 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. 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.
Gastrointestinal disorders Nausea	0.00% 0/73 • 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. 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.	12.5% 3/24 • 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. 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.	0.00% 0/27 • 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. 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.	0.00% 0/13 • 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. 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.
Infections and infestations Candida Intertrigo	0.00% 0/73 • 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. 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.	0.00% 0/24 • 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. 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.	0.00% 0/27 • 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. 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.	7.7% 1/13 • 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. 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.
Reproductive system and breast disorders Vulvovaginitis	2.7% 2/73 • 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. 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.	4.2% 1/24 • 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. 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.	7.4% 2/27 • 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. 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.	7.7% 1/13 • 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. 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.
Reproductive system and breast disorders Vulvovaginal pruritis	1.4% 1/73 • 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. 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.	4.2% 1/24 • 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. 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.	3.7% 1/27 • 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. 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.	15.4% 2/13 • 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. 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.
Reproductive system and breast disorders Vulvovaginal burning	0.00% 0/73 • 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. 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.	0.00% 0/24 • 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. 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.	7.4% 2/27 • 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. 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.	0.00% 0/13 • 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. 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.
Skin and subcutaneous tissue disorders Skin Irritation	0.00% 0/73 • 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. 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.	0.00% 0/24 • 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. 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.	0.00% 0/27 • 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. 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.	7.7% 1/13 • 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. 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.
Gastrointestinal disorders Abdominal Pain	0.00% 0/73 • 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. 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.	12.5% 3/24 • 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. 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.	0.00% 0/27 • 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. 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.	0.00% 0/13 • 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. 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.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Viral Illness	11.0% 8/73 • 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. 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.	16.7% 4/24 • 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. 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.	7.4% 2/27 • 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. 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.	0.00% 0/13 • 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. 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.

Additional Information

Rachel Bender Ignacio, MD MPH

University of Washington

Phone: 2065204340

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place