Recurrent Bacterial Vaginosis
Conditions
Brief summary
The purpose of this study is to test the effectiveness Secnidazole to treat recurrent BV. Secnidazole is approved for one-time use in acute BV. In this study, the drug will be used for recurrent BV, and given weekly for 18 weeks.
Detailed description
A single-center prospective pilot study with once-weekly oral secnidazole granule treatment of acute condition for two-weeks followed by prophylactic treatment of asymptomatic responders with once-weekly secnidazole for 16 weeks, followed by no therapy for 12 weeks. The final follow-up evaluation is at week 28. Eligible women with a current symptomatic bacterial vaginosis infection (\> or = 3 Amsel criteria) and a history of at least 2 previous episodes of bacterial vaginosis in the past year will be enrolled in the open-label treatment study. All women will be treated with 2g of secnidazole granules orally once-weekly for 2 weeks. At the second visit, 3-5 days after completion of treatment, women who have a resolution of bacterial vaginosis (asymptomatic and \< or = 2 Amsel criteria) will continue on once-weekly secnidazole for 16 weeks. Patients will be evaluated every 4 weeks for recurrence of bacterial vaginosis. This will include questions about symptoms as well as a pelvic examination for assessment of vaginal discharge (\> or = 3 Amsel criteria). We will also collect any information on other clinical evaluations for recurrence and the dates of diagnoses and types of treatments they may have received. Those who remain without recurrence during the 16-week suppressive phase will be followed for an additional 12 weeks off therapy, with assessment for recurrence at weeks 22 and 30. Throughout the study, data will be collected on participants' compliance and on the occurrence of adverse events.
Interventions
DRUGSecnidazole 2 GM Oral Granules
Once weekly 2g oral secnidazole for 18 weeks
Sponsors
Lupin Pharmaceuticals, Inc.
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Ability to consent in English * Current symptomatic bacterial vaginosis infection * History of at least 2 previous episodes of bacterial vaginosis in the past year
Exclusion criteria
* Current gynecologic infection or condition, including candida vaginitis, gonorrhea, chlamydia, trichomonas, desquamative inflammatory vaginitis, atrophic vaginitis. * Pre-existing heart conditions * Pre-existing neurological conditions * Currently Pregnant or breastfeeding * Women taking anticoagulants, lithium, metoclopramide, or disulfiram therapy * Hypersensitivity to secnidazole or other drugs in the same class.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Episode of Bacterial Vaginosis | 30 weeks | Overall failure rate as measured by the number of subjects with at least one episode of bacterial vaginosis in the 30 week follow-up period. |
| Probability of Failure at 210 Days | 210 days (30 weeks) | To assess the efficacy of secnidazole, we estimated failure rates and 95% exact confidence intervals for initial treatment, suppression therapy following initial resolution of BV symptoms, and overall. For the time-to-failure analysis, time was defined as the number of days since the second visit where clinical resolution of initial BV was confirmed. The non-parametric maximum likelihood estimate (NPMLE) of the survival curve was estimated using the interval package in R to account for the interval censored data. Results are presented using an Amsel criteria score of as well as for BV diagnosis. All analyses were conducted using R 4.2.2 (R Core Team, 2020) in RStudio (RStudio Team 2021). |
| The Number of Subjects That Failed Treatment in the Supressive Phase | 30 weeks | The probability of recurrence or treatment failure was calculated as time from the second visit in days. This timeframe is the suppressive therapy phase and was 30 weeks long. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Experienced Recurrence 30 Weeks After Start of Initial Treatment | week 30 | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
| Number of Subjects Who Experienced Recurrence 14 Weeks After Start of Initial Treatment | week 14 | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
| Number of Subjects Who Experienced Recurrence 18 Weeks After Start of Initial Treatment | week 18 | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
| Number of Subjects Who Experienced Recurrence 22 Weeks After Start of Initial Treatment | week 22 | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
| Number of Subjects Who Experienced Recurrence 3-5 Days After Initial Treatment (Initial Treatment Was 2 Weeks Long) | 3-5 days after initial treatment after initial treatment of 2 weeks | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
| Number of Subjects Who Experienced Recurrence 6 Weeks After Start of Initial Treatment | week 6 | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
| Number of Subjects Who Experienced Recurrence 10 Weeks After Start of Initial Treatment | week 10 | Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tolerance | 18 weeks | Subject tolerance with the study medication, based on questionnaire that asked if the participant took the medication as scheduled and asked about side effects. |
| Number of Adverse Events | 30 weeks | Number of adverse events that participants experienced |
| Number of Participant With Compliance | 18 weeks | Subject compliance with the study medication, based on questionnaire that asked if the participant took the medication as scheduled and asked about side effects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Secnidazole prescribed once-weekly secnidazole for 16 weeks as prophylactic treatment | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Secnidazole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 35.3 years STANDARD_DEVIATION 9.8 |
| Bacterial Vaginosis (BV) episodes in prior 12 months | 8.1 episodes STANDARD_DEVIATION 6.4 |
| Race/Ethnicity, Customized Black | 16 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 10 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Number of Subjects With at Least One Episode of Bacterial Vaginosis
Overall failure rate as measured by the number of subjects with at least one episode of bacterial vaginosis in the 30 week follow-up period.
Time frame: 30 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects With at Least One Episode of Bacterial Vaginosis | 8 Participants |
Primary
Probability of Failure at 210 Days
To assess the efficacy of secnidazole, we estimated failure rates and 95% exact confidence intervals for initial treatment, suppression therapy following initial resolution of BV symptoms, and overall. For the time-to-failure analysis, time was defined as the number of days since the second visit where clinical resolution of initial BV was confirmed. The non-parametric maximum likelihood estimate (NPMLE) of the survival curve was estimated using the interval package in R to account for the interval censored data. Results are presented using an Amsel criteria score of as well as for BV diagnosis. All analyses were conducted using R 4.2.2 (R Core Team, 2020) in RStudio (RStudio Team 2021).
Time frame: 210 days (30 weeks)
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Probability of Failure at 210 Days | 0.7051 Probability |
Primary
The Number of Subjects That Failed Treatment in the Supressive Phase
The probability of recurrence or treatment failure was calculated as time from the second visit in days. This timeframe is the suppressive therapy phase and was 30 weeks long.
Time frame: 30 weeks
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | The Number of Subjects That Failed Treatment in the Supressive Phase | 3 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 10 Weeks After Start of Initial Treatment
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: week 10
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 10 Weeks After Start of Initial Treatment | 0 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 14 Weeks After Start of Initial Treatment
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: week 14
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 14 Weeks After Start of Initial Treatment | 1 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 18 Weeks After Start of Initial Treatment
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: week 18
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 18 Weeks After Start of Initial Treatment | 1 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 22 Weeks After Start of Initial Treatment
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: week 22
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 22 Weeks After Start of Initial Treatment | 2 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 30 Weeks After Start of Initial Treatment
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: week 30
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 30 Weeks After Start of Initial Treatment | 3 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 3-5 Days After Initial Treatment (Initial Treatment Was 2 Weeks Long)
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: 3-5 days after initial treatment after initial treatment of 2 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 3-5 Days After Initial Treatment (Initial Treatment Was 2 Weeks Long) | 5 Participants |
Secondary
Number of Subjects Who Experienced Recurrence 6 Weeks After Start of Initial Treatment
Recurrence was measured using the Amsel criteria. The Amsel criteria are: 1) Homogenous white discharge, 2) pH \> 4.5, 3) amine odor (whiff) test, 4) clue cells on microscopy
Time frame: week 6
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Subjects Who Experienced Recurrence 6 Weeks After Start of Initial Treatment | 0 Participants |
Other Pre-specified
Number of Adverse Events
Number of adverse events that participants experienced
Time frame: 30 weeks
Population: Analysis only includes participants who experienced an AE.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Number of Adverse Events | 41 adverse events |
Other Pre-specified
Number of Participants With Tolerance
Subject tolerance with the study medication, based on questionnaire that asked if the participant took the medication as scheduled and asked about side effects.
Time frame: 18 weeks
Population: This number of participants includes all subjects, including lost to follow up and withdraws. Only one subject reported intolerance of the medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participants With Tolerance | 24 Participants |
Other Pre-specified
Number of Participant With Compliance
Subject compliance with the study medication, based on questionnaire that asked if the participant took the medication as scheduled and asked about side effects.
Time frame: 18 weeks
Population: The calculation only includes participants who began the suppression portion of the study and participants who were not withdrawn or lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participant With Compliance | 15 Participants |