Bacterial Vaginosis
Conditions
Keywords
Bacterial vaginosis, Candida albicans, Double-Blind, Gardnerella vaginalis, Phase II, Placebo, Randomized, Suppression, TOL-463 insert
Brief summary
A Phase II randomized, double-blind, placebo-controlled study screening approximately 600 adult females, aged 18-55, with a goal to enroll approximately 250 participants to achieve 200 evaluable participants at the test of cure (TOC) visit. The study is designed to determine the clinical efficacy of an investigational product (IP), TOL-463 Insert, in suppressing Recurrent Bacterial Vaginosis (RBV) when administered to women who have a history of RBV and have been successfully cleared of their current Bacterial Vaginosis (BV) infection administering 500 mg of oral metronidazole, twice a day for 7 days or another CDC-recommended BV treatment. Patient participation will be approximately 100 days while the study is conducted at 4 sites within the United States. The primary objective of the study is to evaluate the clinical efficacy of a twice-weekly application of TOL-463 vaginal insert in suppression of BV in women with a history of RBV following successful induction with oral metronidazole or a CDC-recommended BV treatment.
Detailed description
This is a Phase II randomized, double-blind, placebo-controlled study screening approximately 600 adult females, aged 18-55, with a goal to enroll approximately 250 participants to achieve 200 evaluable participants at the test of cure (TOC) visit. The study is designed to determine the clinical efficacy of an investigational product (IP), TOL-463 Insert, in suppressing Recurrent Bacterial Vaginosis (RBV) when administered to women who have a history of RBV and have been successfully cleared of their current Bacterial Vaginosis (BV) infection administering 500 mg of oral metronidazole, twice a day for 7 days or another CDC-recommended BV treatment. Patient participation will be approximately 100 days while the study is conducted at 4 sites within the United States. The primary objective of the study is to evaluate the clinical efficacy of a twice-weekly application of TOL-463 vaginal insert in suppression of BV in women with a history of RBV following successful induction with oral metronidazole or a CDC-recommended BV treatment. Secondary objectives of the study are: 1) to evaluate the time to BV recurrence as defined by clinical criteria, 2) to evaluate the incidence of vaginal symptoms over study participation, 3) to evaluate acceptability of a twice-weekly application of TOL-463 vaginal insert in suppression of BV, and 4) to evaluate the safety of TOL-463 vaginal insert compared to placebo, including the incidence of secondary vulvovaginal candidiasis (VVC). The null hypothesis for the comparison is that there is no difference in cure rates between treatments, with a two-sided alternative.
Interventions
OTHERPlacebo
Placebo vaginal inserts.
DRUGTOL-463
TOL-463 is a non-azole vaginal anti-infective drug candidate designed as a dual-indication therapy for BV and VVC.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Screening Visit(s) Inclusion Criteria: 1. Women with a current Bacterial Vaginosis (BV) infection and a history of at least two previous episodes of BV by documentation or self-report in the past year. Screening (V0) diagnosis is based on the presence of \> / = 3 Amsel criteria\*; * Homogeneous vaginal discharge; positive potassium hydroxide (KOH) whiff test; vaginal pH of \> 4.5; and \> / = 20% clue cells. 2. Willing and able to provide written informed consent; 3. Age 18-55 years of age at the time of V0; 4. General good health based on medical history, targeted physical examination, and pelvic examination; 5. For participants 21 years of age or older, Pap test performed within the past 3 years, with the most recent result being normal or Atypical Squamous Cells of Undetermined Significance (ASCUS) Human Papillomavirus (HPV) negative or Pap smear collected at V0\*; \*Consistent with current Pap screening guidelines, a Pap smear must be performed at V0, for women who meet the following criteria and cannot provide documentation or self-report of a normal or ASCUS HPV negative Pap smear, conducted within the prior 3 years: (a) has not had a hysterectomy or (b) has had a hysterectomy and has a history of cervical intraepithelial neoplasia grade 2 plus (CIN2plus) in the past 20 years. Note: If a Pap smear is conducted at V0, the results are not required prior to enrollment. 6. Have a negative urine pregnancy test at V0, if of childbearing potential; 7. Must be of non-childbearing potential\* or must be using an effective method of birth control\*\* and must be willing to continue the method through the end of Investigational Product (IP) administration; \*Defined as post-menopausal or status post bilateral tubal ligation, or status post bilateral oophorectomy or status post hysterectomy. \*\*Acceptable methods are defined as: 1. Intrauterine Devices (IUDs) or hormonal contraceptives for at least 22 days prior to screening. Note: Intravaginal contraceptive rings (e.g., NuvaRing) are not acceptable forms of birth control for this study. 2. Consistent use of a barrier method, including diaphragms or condoms, for at least 13 days prior to screening. 3. Abstinence from vaginal sexual intercourse for at least 13 days prior to screening. 4. Exclusively same-sex relationship. 5. Monogamous relationship with vasectomized partner. 8. Willing and able to cooperate to the extent and degree required by this protocol at the discretion of the investigator; Enrollment Visit Inclusion Criteria: In addition to confirming all relevant Screening Visit Inclusion Criteria, women must meet all of the following criteria to be eligible for enrollment in the study. 1. Willing and able to provide Enrollment written informed consent; 2. After completion of metronidazole induction therapy or another CDC-recommended BV treatment, no clinical evidence of BV\* and absence of symptoms of BV\*\* at Visit 1, Enrollment (V1); * As defined by \< / = 2 of 4 Amsel criteria. \*\*Defined as absence of vaginal discharge and odor consistent with BV. 3. Must have a negative urine pregnancy test at V1, if of childbearing potential; 4. Willing to refrain from any intravaginal products/medications\* other than the IP throughout the course of the trial; \*For example: douches, antifungal or antibacterial preparations, lubricants, contraceptive creams, gels, foams, sponges, spermicides. 5. Must agree to abstain from receptive oral, anal, and vaginal sexual intercourse one hour prior to IP administration and for 24 hours after; 6. Willing to refrain from using tampons or menstrual cups for 24 hours after IP administration; 7. Must be of non-childbearing potential\* OR must be using an effective method of birth control\*\* and must be willing to continue the method through the end of IP administration; \*Defined as post-menopausal or status post bilateral tubal ligation, or status post bilateral oophorectomy or status post hysterectomy. * Acceptable methods are defined as: 1. IUDs or hormonal contraceptives for at least 30 days prior to using IP. Note: Intravaginal contraceptive rings (e.g., NuvaRing) are not acceptable forms of birth control for this study. 2. Consistent use of a barrier method, including diaphragms or condoms, for at least 21 days prior to using IP. 3. Abstinence from vaginal sexual intercourse for at least 21 days prior to using IP. 4. Exclusively same-sex relationship. 5. Monogamous relationship with vasectomized partner.
Exclusion criteria
Screening Visit(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Recurrent Bacterial Vaginosis (RBV) by Visit 4, as Defined by Presence of at Least 3 Amsel Criteria | Day 1 through Day 91 | Recurrent bacterial vaginosis (RBV) was defined as the presence of at least three out of the following four Amsel criteria: positive KOH whiff test, homogeneous discharge characteristic of BV, clue cells comprising at least 20% of vaginal squamous epithelial cells, and vaginal pH \> 4.5. Participants who had post-baseline efficacy results but were lost to follow-up before study completion were considered treatment failures and counted toward the number of participants with recurrence of BV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Bacterial Vaginosis (BV) Recurrence, as Defined by Presence of at Least 3 Amsel Criteria | Day 1 through Day 91 | Recurrent bacterial vaginosis (RBV) was defined as the presence of at least three out of the following four Amsel criteria: positive KOH whiff test, homogeneous discharge characteristic of BV, clue cells comprising at least 20% of vaginal squamous epithelial cells, and vaginal pH \> 4.5. Participants who had post-baseline efficacy results but were lost to follow-up before study completion were censored in secondary time-to-event analyses. Participants with off-study diagnosis of BV were excluded from secondary time-to-event analyses. The median time to BV recurrence was calculated as the first event time at which the Kaplan-Meier estimator drops to or below 0.5. |
| Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Assessed at Visit 1 (Day 1), Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) and Visit 4 (Window: Days 85-91). | The BV symptoms evaluated for efficacy at each clinic visit included abnormal vaginal discharge and vaginal odor. Both symptoms were assessed by a clinician as either consistent with BV, not consistent with BV, or absent. Only symptoms deemed consistent with BV were reported as BV symptoms. |
| Number of Participants With Culture Confirmed Secondary VVC Following Initiation of Study Treatment | Day 1 through Day 91 | Assessment of vulvovaginal candidiasis (VVC) was performed by pelvic examination at baseline and at each follow-up visit. If clinical diagnosis of VVC was determined at any visit, then a confirmatory Candida culture was performed. |
| Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Assessed at study completion (the visit at which the participant was diagnosed with BV, or Visit 4 for participants remaining BV suppressed). This may occur at Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) or Visit 4 (Window: Days 85-91). | The satisfaction questionnaire contained five questions assessing participant satisfaction with the study treatment. For questions regarding ease of use, frequency of use, and overall satisfaction, participants could respond on a scale ranging from Extremely dissatisfied to Extremely satisfied. Participants who responded with Somewhat satisfied through Extremely satisfied were considered Satisfied with those categories. For the question regarding convenience of use, participants could respond on a scale ranging from Extremely inconvenient to Extremely convenient. Participants who responded with Somewhat convenient through Extremely convenient were considered Satisfied with study treatment convenience. For the question of whether the participant would use the study treatment again, participants who responded with Yes were considered Satisfied with the study treatment. |
| Number of Participants With Adverse Events (AEs) Considered Product-related Following Initiation of Study Treatment | Day 1 through Day 91 | Safety was monitored throughout the study, including via participant reporting. Study clinicians assessed whether or not reported adverse events (AEs) were related to study treatment. |
| Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Assessed at Visit 1 (Day 1), Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) and Visit 4 (Window: Days 85-91). | The BV symptoms evaluated for efficacy at each clinic visit included abnormal vaginal discharge and vaginal odor. Both symptoms were assessed by a clinician as either consistent with BV, not consistent with BV, or absent. Only symptoms deemed consistent with BV were reported as BV symptoms. |
Countries
United States
Participant flow
Recruitment details
Participants were adult females 18-55 years of age with a history of recurrent bacterial vaginosis. Participants were recruited from United States health clinics and enrolled between 09SEP2019 and 20SEP2021
Participants by arm
| Arm | Count |
|---|---|
| TOL-463 Vaginal Insert TOL-463 Vaginal Insert administered vaginally as a single 2 gram unit dose twice a week with a minimum of a two-day duration in between doses for twelve weeks with the aid of a disposable applicator. | 40 |
| Placebo Placebo administered vaginally as a single 2 gram (g) unit dose twice a week with a minimum of a two-day duration in between doses for twelve weeks with the aid of a disposable applicator. | 41 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | COVID-19 Shelter in Place Order | 3 | 5 |
| Overall Study | Lost to Follow-up | 10 | 5 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | TOL-463 Vaginal Insert | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 7.3 | 33.5 years STANDARD_DEVIATION 7.5 | 34.0 years STANDARD_DEVIATION 7.8 |
| Culture Confirmed Vulvovaginal Candidiasis (VVC) Status at Baseline Negative | 36 Participants | 71 Participants | 35 Participants |
| Culture Confirmed Vulvovaginal Candidiasis (VVC) Status at Baseline Positive | 4 Participants | 9 Participants | 5 Participants |
| Culture Confirmed Vulvovaginal Candidiasis (VVC) Status at Baseline Unknown | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 9 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 72 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of BV Occurrences in Past 12 Months Prior to Screening | 5.3 occurrences STANDARD_DEVIATION 2.5 | 5.1 occurrences STANDARD_DEVIATION 2.6 | 4.9 occurrences STANDARD_DEVIATION 2.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 51 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) White | 5 Participants | 16 Participants | 11 Participants |
| Region of Enrollment United States | 40 participants | 81 participants | 41 participants |
| Sex: Female, Male Female | 40 Participants | 81 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 41 |
| other Total, other adverse events | 13 / 40 | 9 / 41 |
| serious Total, serious adverse events | 0 / 40 | 0 / 41 |
Outcome results
Primary
Proportion of Participants With Recurrent Bacterial Vaginosis (RBV) by Visit 4, as Defined by Presence of at Least 3 Amsel Criteria
Recurrent bacterial vaginosis (RBV) was defined as the presence of at least three out of the following four Amsel criteria: positive KOH whiff test, homogeneous discharge characteristic of BV, clue cells comprising at least 20% of vaginal squamous epithelial cells, and vaginal pH \> 4.5. Participants who had post-baseline efficacy results but were lost to follow-up before study completion were considered treatment failures and counted toward the number of participants with recurrence of BV.
Time frame: Day 1 through Day 91
Population: The modified intent-to-treat (mITT) population includes all randomized participants with negative STI results at screening and, for participants 21 years and older, either a normal or atypical squamous cells of undetermined significance (ASCUS) HPV-negative Pap test performed at screening or within the past 3 years. This analysis includes all participants in the mITT population except those with no post-baseline efficacy data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TOL-463 Vaginal Insert | Proportion of Participants With Recurrent Bacterial Vaginosis (RBV) by Visit 4, as Defined by Presence of at Least 3 Amsel Criteria | 0.581 proportion of participants |
| Placebo | Proportion of Participants With Recurrent Bacterial Vaginosis (RBV) by Visit 4, as Defined by Presence of at Least 3 Amsel Criteria | 0.697 proportion of participants |
Secondary
Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses
The satisfaction questionnaire contained five questions assessing participant satisfaction with the study treatment. For questions regarding ease of use, frequency of use, and overall satisfaction, participants could respond on a scale ranging from Extremely dissatisfied to Extremely satisfied. Participants who responded with Somewhat satisfied through Extremely satisfied were considered Satisfied with those categories. For the question regarding convenience of use, participants could respond on a scale ranging from Extremely inconvenient to Extremely convenient. Participants who responded with Somewhat convenient through Extremely convenient were considered Satisfied with study treatment convenience. For the question of whether the participant would use the study treatment again, participants who responded with Yes were considered Satisfied with the study treatment.
Time frame: Assessed at study completion (the visit at which the participant was diagnosed with BV, or Visit 4 for participants remaining BV suppressed). This may occur at Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) or Visit 4 (Window: Days 85-91).
Population: The modified intent-to-treat (mITT) population includes all randomized participants with negative STI results at screening and, for participants 21 years and older, either a normal or atypical squamous cells of undetermined significance (ASCUS) HPV-negative Pap test performed at screening or within the past 3 years. This analysis includes all participants in the mITT population who completed the satisfaction questionnaire.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Ease of use | Satisfied | 25 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Ease of use | Not Satisfied | 2 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Frequency of use | Satisfied | 25 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Frequency of use | Not Satisfied | 2 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Convenience of use | Satisfied | 26 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Convenience of use | Not Satisfied | 1 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Overall satisfaction | Satisfied | 26 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Overall satisfaction | Not Satisfied | 1 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Would use study treatment again | Satisfied | 25 Participants |
| TOL-463 Vaginal Insert | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Would use study treatment again | Not Satisfied | 2 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Overall satisfaction | Not Satisfied | 8 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Ease of use | Satisfied | 28 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Convenience of use | Not Satisfied | 4 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Ease of use | Not Satisfied | 5 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Would use study treatment again | Not Satisfied | 7 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Frequency of use | Satisfied | 33 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Overall satisfaction | Satisfied | 25 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Frequency of use | Not Satisfied | 0 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Would use study treatment again | Satisfied | 26 Participants |
| Placebo | Number of Participants Satisfied With the Study Treatment as Assessed by Satisfaction Questionnaire Responses | Convenience of use | Satisfied | 29 Participants |
Secondary
Number of Participants With Adverse Events (AEs) Considered Product-related Following Initiation of Study Treatment
Safety was monitored throughout the study, including via participant reporting. Study clinicians assessed whether or not reported adverse events (AEs) were related to study treatment.
Time frame: Day 1 through Day 91
Population: The Safety population includes all randomized participants who received at least one dose of study treatment. Participants with any evidence of dosing according to memory aid or study IP packaging return were included in the Safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TOL-463 Vaginal Insert | Number of Participants With Adverse Events (AEs) Considered Product-related Following Initiation of Study Treatment | 11 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) Considered Product-related Following Initiation of Study Treatment | 10 Participants |
Secondary
Number of Participants With Culture Confirmed Secondary VVC Following Initiation of Study Treatment
Assessment of vulvovaginal candidiasis (VVC) was performed by pelvic examination at baseline and at each follow-up visit. If clinical diagnosis of VVC was determined at any visit, then a confirmatory Candida culture was performed.
Time frame: Day 1 through Day 91
Population: The Safety population includes all randomized participants who received at least one dose of study treatment. Participants with any evidence of dosing according to memory aid or study IP packaging return were included in the Safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TOL-463 Vaginal Insert | Number of Participants With Culture Confirmed Secondary VVC Following Initiation of Study Treatment | 0 Participants |
| Placebo | Number of Participants With Culture Confirmed Secondary VVC Following Initiation of Study Treatment | 3 Participants |
Secondary
Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge
The BV symptoms evaluated for efficacy at each clinic visit included abnormal vaginal discharge and vaginal odor. Both symptoms were assessed by a clinician as either consistent with BV, not consistent with BV, or absent. Only symptoms deemed consistent with BV were reported as BV symptoms.
Time frame: Assessed at Visit 1 (Day 1), Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) and Visit 4 (Window: Days 85-91).
Population: The modified intent-to-treat (mITT) population includes all randomized participants with negative STI results at screening and, for participants 21 years and older, either a normal or atypical squamous cells of undetermined significance (ASCUS) HPV-negative Pap test performed at screening or within the past 3 years. This analysis includes all participants in the mITT population with data available from the corresponding visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 1 | 0.025 proportion of participants |
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 2 | 0.091 proportion of participants |
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 3 | 0.056 proportion of participants |
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 4 | 0.000 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 4 | 0.000 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 1 | 0.000 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 3 | 0.063 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Abnormal Vaginal Discharge | Visit 2 | 0.114 proportion of participants |
Secondary
Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor
The BV symptoms evaluated for efficacy at each clinic visit included abnormal vaginal discharge and vaginal odor. Both symptoms were assessed by a clinician as either consistent with BV, not consistent with BV, or absent. Only symptoms deemed consistent with BV were reported as BV symptoms.
Time frame: Assessed at Visit 1 (Day 1), Visit 2 (Window: Days 29-35), Visit 3 (Window: Days 57-63) and Visit 4 (Window: Days 85-91).
Population: The modified intent-to-treat (mITT) population includes all randomized participants with negative STI results at screening and, for participants 21 years and older, either a normal or atypical squamous cells of undetermined significance (ASCUS) HPV-negative Pap test performed at screening or within the past 3 years. This analysis includes all participants in the mITT population with data available from the corresponding visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 1 | 0.025 proportion of participants |
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 2 | 0.152 proportion of participants |
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 3 | 0.056 proportion of participants |
| TOL-463 Vaginal Insert | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 4 | 0.000 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 4 | 0.100 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 1 | 0.024 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 3 | 0.125 proportion of participants |
| Placebo | Proportion of Participants Reporting Bacterial Vaginosis (BV) Symptoms - Vaginal Odor | Visit 2 | 0.143 proportion of participants |
Secondary
Time to Bacterial Vaginosis (BV) Recurrence, as Defined by Presence of at Least 3 Amsel Criteria
Recurrent bacterial vaginosis (RBV) was defined as the presence of at least three out of the following four Amsel criteria: positive KOH whiff test, homogeneous discharge characteristic of BV, clue cells comprising at least 20% of vaginal squamous epithelial cells, and vaginal pH \> 4.5. Participants who had post-baseline efficacy results but were lost to follow-up before study completion were censored in secondary time-to-event analyses. Participants with off-study diagnosis of BV were excluded from secondary time-to-event analyses. The median time to BV recurrence was calculated as the first event time at which the Kaplan-Meier estimator drops to or below 0.5.
Time frame: Day 1 through Day 91
Population: The modified intent-to-treat (mITT) population includes all randomized participants with negative STI results at screening and, for participants 21 years and older, either a normal or atypical squamous cells of undetermined significance (ASCUS) HPV-negative Pap test performed at screening or within the past 3 years. This analysis includes all participants in the mITT population, excluding those with no post-baseline efficacy data available and those diagnosed with BV off-study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TOL-463 Vaginal Insert | Time to Bacterial Vaginosis (BV) Recurrence, as Defined by Presence of at Least 3 Amsel Criteria | NA days |
| Placebo | Time to Bacterial Vaginosis (BV) Recurrence, as Defined by Presence of at Least 3 Amsel Criteria | 46 days |