Vaginal Infection
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of terconazole/metronidazole gel in the treatment of vaginal infections
Interventions
Sponsors
Curatek Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A clinical diagnosis of vaginal infection that is confirmed by laboratory testing and: * Capable of providing written informed consent or assent * Currently not menstruating and not anticipating menses during treatment * If heterosexually active, subject must be post-menopausal for ≥ 1 year, surgically sterile, or practicing an acceptable form of birth control * Negative pregnancy test * Other criteria as identified in the protocol
Exclusion criteria
* Other infectious causes of vulvovaginitis * Subject has recently used, or is expected to require the concomitant use of prohibited medications/products * Nursing mother * Use of any investigational drug within 30 days of enrollment * History of hypersensitivity to any ingredient/component of the formulations * Other criteria as identified in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit | 7-14 days after beginning treatment | The percentage of participants with clinical cure of both bacterial vaginosis (BV) AND vulvovaginal candidiasis (VVC) was compared between the combination therapy and the two single entity treatments. Clinical cure of BV is defined as: discharge has returned to normal/physiologic, negative whiff test, and saline wet mount is \<20% clue cells. Clinical cure of VVC is defined as resolution of all signs and symptoms attributable to vulvovaginal candidiasis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cure of the BV Component of Mixed Infection | 7-14 days after beginning treatment | The percentage of participants with both BV and VVC who had clinical cure of bacterial vaginosis (BV) was compared between the combination therapy and the two single entity treatments. Clinical cure of BV was defined as: 1. discharge has returned to normal/physiologic, 2. the whiff test is negative for any amine fishy odor, 3. the saline wet mount is \<20% clue cells |
| Cure of the VVC Component of Mixed Infection | 7-14 days after beginning treatment | The percentage of participants with both BV and VVC who had clinical cure of VVC was compared between the combination therapy and the two single entity treatments.Clinical cure of VVC was defined as complete resolution of all signs and symptoms attributable to VVC |
| Microbiologic and Mycologic Cure | 7-14 days after beginning treatment | The percentage of participants with both microbiologic and mycologic cure was compared between the combination therapy and the two single entity treatments. Yeast cultures were performed and Gram stains of vaginal fluid were graded according to Nugent's criteria. Microbiologic cure requires normal Nugent gram stain score and mycologic cure requires negative yeast culture. |
| Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit | 7-14 days after beginning treatment | Subjects reported if symptoms completely resolved and the date of resolution. The percentage of participants reporting complete resolution of symptoms was compared between arms. |
| Number of Participants With Treatment Emergent Adverse Events | Any time during study participation (up to 30 days) | Adverse events were collected at study visits, from subject diaries and from spontaneous reports |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Terconazole Vaginal Gel One applicator full at bedtime
Terconazole | 83 |
| Metronidazole Vaginal Gel One applicator full at bedtime
Metronidazole | 84 |
| Terconazole/Metronidazole Vaginal Gel One applicator full at bedtime
Terconazole/metronidazole | 82 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 | 1 |
| Overall Study | Normal Gram stain or neg yeast culture | 66 | 64 | 67 |
| Overall Study | Positive for STD at Baseline | 7 | 11 | 7 |
Baseline characteristics
| Characteristic | Terconazole Vaginal Gel | Total | Terconazole/Metronidazole Vaginal Gel | Metronidazole Vaginal Gel |
|---|---|---|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 9.17 | 31.7 years STANDARD_DEVIATION 9.72 | 32.6 years STANDARD_DEVIATION 10.57 | 31.0 years STANDARD_DEVIATION 9.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 39 Participants | 9 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants | 210 Participants | 73 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants | 156 Participants | 50 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 84 Participants | 28 Participants | 26 Participants |
| Region of Enrollment United States | 83 participants | 249 participants | 82 participants | 84 participants |
| Sex: Female, Male Female | 83 Participants | 249 Participants | 82 Participants | 84 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 149 | 0 / 151 | 0 / 154 |
| other Total, other adverse events | 5 / 149 | 6 / 151 | 8 / 154 |
| serious Total, serious adverse events | 1 / 149 | 0 / 151 | 0 / 154 |
Outcome results
Primary
Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit
The percentage of participants with clinical cure of both bacterial vaginosis (BV) AND vulvovaginal candidiasis (VVC) was compared between the combination therapy and the two single entity treatments. Clinical cure of BV is defined as: discharge has returned to normal/physiologic, negative whiff test, and saline wet mount is \<20% clue cells. Clinical cure of VVC is defined as resolution of all signs and symptoms attributable to vulvovaginal candidiasis
Time frame: 7-14 days after beginning treatment
Population: mITT population (Baseline Nugent Gram stain score of 4 or more, and positive baseline yeast culture, and used at least one dose of study medication)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Terconazole Vaginal Gel | Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit | 31 Participants |
| Metronidazole Vaginal Gel | Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit | 29 Participants |
| Terconazole/Metronidazole Vaginal Gel | Clinical Cure of Mixed Infection (BV and VVC) as Assessed by the Investigator at the Test-of-cure Visit | 43 Participants |
p-value: 0.03Chi-squared, Corrected
p-value: 0.073Chi-squared, Corrected
Comparison: Stratified by race (black, white, or other race)p-value: 0.0204Cochran-Mantel-Haenszel
Comparison: Stratified by race (black, white, or other race)p-value: 0.0493Cochran-Mantel-Haenszel
Secondary
Cure of the BV Component of Mixed Infection
The percentage of participants with both BV and VVC who had clinical cure of bacterial vaginosis (BV) was compared between the combination therapy and the two single entity treatments. Clinical cure of BV was defined as: 1. discharge has returned to normal/physiologic, 2. the whiff test is negative for any amine fishy odor, 3. the saline wet mount is \<20% clue cells
Time frame: 7-14 days after beginning treatment
Population: mITT population (Baseline Nugent Gram stain score of 4 or more, and positive baseline yeast culture, and used at least one dose of study medication)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Terconazole Vaginal Gel | Cure of the BV Component of Mixed Infection | 38 Participants |
| Metronidazole Vaginal Gel | Cure of the BV Component of Mixed Infection | 46 Participants |
| Terconazole/Metronidazole Vaginal Gel | Cure of the BV Component of Mixed Infection | 54 Participants |
p-value: 0.015Chi-squared, Corrected
Comparison: Difference for Terconazole/metronidazole vaginal gel cures minus metronidazole vaginal gel curesp-value: 0.193Chi-squared, Corrected
Secondary
Cure of the VVC Component of Mixed Infection
The percentage of participants with both BV and VVC who had clinical cure of VVC was compared between the combination therapy and the two single entity treatments.Clinical cure of VVC was defined as complete resolution of all signs and symptoms attributable to VVC
Time frame: 7-14 days after beginning treatment
Population: mITT population (Baseline Nugent Gram stain score of 4 or more, and positive baseline yeast culture, and used at least one dose of study medication)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Terconazole Vaginal Gel | Cure of the VVC Component of Mixed Infection | 52 Participants |
| Metronidazole Vaginal Gel | Cure of the VVC Component of Mixed Infection | 37 Participants |
| Terconazole/Metronidazole Vaginal Gel | Cure of the VVC Component of Mixed Infection | 53 Participants |
p-value: 0.012Chi-squared, Corrected
p-value: 0.918Chi-squared, Corrected
Secondary
Microbiologic and Mycologic Cure
The percentage of participants with both microbiologic and mycologic cure was compared between the combination therapy and the two single entity treatments. Yeast cultures were performed and Gram stains of vaginal fluid were graded according to Nugent's criteria. Microbiologic cure requires normal Nugent gram stain score and mycologic cure requires negative yeast culture.
Time frame: 7-14 days after beginning treatment
Population: mITT population (Baseline Nugent Gram stain score of 4 or more, and positive baseline yeast culture, and used at least one dose of study medication)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Terconazole Vaginal Gel | Microbiologic and Mycologic Cure | 19 Participants |
| Metronidazole Vaginal Gel | Microbiologic and Mycologic Cure | 5 Participants |
| Terconazole/Metronidazole Vaginal Gel | Microbiologic and Mycologic Cure | 24 Participants |
Secondary
Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit
Subjects reported if symptoms completely resolved and the date of resolution. The percentage of participants reporting complete resolution of symptoms was compared between arms.
Time frame: 7-14 days after beginning treatment
Population: mITT population (Baseline Nugent Gram stain score of 4 or more, and positive baseline yeast culture, and used at least one dose of study medication)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Terconazole Vaginal Gel | Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit | 49 Participants |
| Metronidazole Vaginal Gel | Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit | 44 Participants |
| Terconazole/Metronidazole Vaginal Gel | Number of Participants Reporting Complete Resolution of Symptoms by Test of Cure Visit | 49 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events
Adverse events were collected at study visits, from subject diaries and from spontaneous reports
Time frame: Any time during study participation (up to 30 days)
Population: Safety population, defined as all subjects randomized to treatment and administered at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Terconazole Vaginal Gel | Number of Participants With Treatment Emergent Adverse Events | 44 Participants |
| Metronidazole Vaginal Gel | Number of Participants With Treatment Emergent Adverse Events | 40 Participants |
| Terconazole/Metronidazole Vaginal Gel | Number of Participants With Treatment Emergent Adverse Events | 44 Participants |