BACTERIAL VAGINOSIS, Signs and Symptoms to be Evaluated and Recorded Include, Vaginal Discharge Color, Odor, and Consistency, Vulvovaginal Inflammation (Objective) Absent, Mild, Moderate, or Severe, Vulvovaginal Itching and Irritation (Subjective) Absent, Mild, Moderate, or Severe
Conditions
Brief summary
A multi-center, double-blind, randomized, placebo controlled, parallel-group study, comparing Clindamycin phosphate vaginal cream 2% (Watson Laboratories, Inc.) to Clindesse® (Ther-Rx™, Clindamyin Phosphate Vaginal Cream 2%) and both active treatments to a placebo control in the treatment of bacterial vaginosis in non-pregnant women.
Detailed description
The study treatment period will be 1 day. Subject participation is 22-30 days. Expected study duration is 10 to 12 months. The study will enroll in up to 30 clinical sites. Test Product: One single-dose, pre-filled disposable applicator delivering approximately 5 g of cream containing approximately 100 mg of clindamycin phosphate vaginal cream 2% (Watson Laboratories, Inc.) Reference Product: One single-dose, pre-filled disposable applicator delivering approximately 5 g of cream containing approximately 100 mg of Clindesse® (clindamycin phosphate vaginal cream 2% ) (Ther-Rx™) Placebo Control: One single-dose, pre-filled disposable applicator delivering approximately 5 g of cream containing vehicle of the test product (Watson Laboratories, Inc.) Dose and Mode A single applicator of investigational product cream will be administered of Administration once intravaginally at any time of the day. The subject participation is 22-30 days (drug administration for 1 day).
Interventions
DRUGclindamycin phosphate vaginal cream 2%
OTHERplacebo
vehicle used as placebo
Sponsors
Watson Laboratories, Inc.
Actavis Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must be willing and able to understand and comply with the requirements of the protocol, including attendance at the required study visits and must provide the written informed consent prior to any study related procedure being performed. 2. Healthy non-pregnant female aged ≥ 18 years with no known medical conditions that, in the investigator's opinion, may interfere with study participation or may interfere with the evaluation of bacterial vaginosis. 3. Female subjects of childbearing potential (excluding women who are surgically sterilized or postmenopausal for at least 1 year), in addition to having a negative urine pregnancy test must be willing to use an acceptable form of birth control during the study from the day of the first dose administration to the Visit 2 Test-of-cure. For the purpose of this study the following are considered acceptable methods of birth control: * Oral or injectable contraceptives * Contraceptive patches * Depo-Provera® (stabilized for at least 3 months); Implanon™ (contraceptive implant), or abstinence with one of the above-listed methods of birth control should the Subject become sexually active. * A sterile sexual partner is NOT considered an adequate form of birth control. * Willing to refrain from sexual intercourse on study days 1-7 and for 48 hours prior to Visit 2 Test-of-cure. 4. Willing to refrain from using any vaginal product (e.g., spermicide, tampon, douche, diaphragm, or condom) other than study product, on study Days 1-7, for 48 hours prior to the first dose of study product, and for 48 hours prior to Visit 2 Test-of-cure. 5. Diagnosis of bacterial vaginosis, defined as the presence of all of the following: * Clinical diagnosis of bacterial vaginosis (e.g., thin, homogenous vaginal discharge associated with minimal or absent pruritus or inflammation AND * Saline wet mount of vaginal discharge demonstrating the proportion of clue cell to be ≥ 20% of the total epithelial cells AND * Vaginal pH \> 4.5, using pH paper that measures from 4.0-6.0 AND * Positive whiff test after addition of a drop of 10% KOH to vaginal discharge) * Gram stain Nugent score ≥ 4 on first day of dosing (study day 1) (per Table 1 below). * Table 1: Nugent Scoring System (0-10) for Gram-stained Vaginal Smears (a) * Score (b) Lactobacillus morphotypes Gardnerella and Bacteroides spp. morphotypes Curved gram-variable rods * 0 4+ 0 0 * 1 3+ 1+ 1+ or 2+ * 2 2+ 2+ 3+ or 4+ * 3 1+ 3+ * 4 0 4+ Source: Nugent, R. P., M. A. Krohn, and S. L. Hillier. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J. Clin. Microbial. 1991; 29: 297-301. * Morphotypes are scored as the average number seen per oil immersion field. Note that less weight is given to curved gram-variable rods. Total score = lactobacilli + G. vaginalis and Bacteroides spp/ + curved rods. * 0, No morphotypes present; 1, \<1 morphotype present; 2, 1 to 4 morphotypes present; 3, 5 to 30 morphotypes present; 4, 30 or more morphotypes present.
Exclusion criteria
1. Female subjects who are pregnant, nursing or planning to become pregnant during study participation. 2. Menstruating when diagnosis of bacterial vaginosis is determined at Baseline visit. 3. Primary or secondary immunodeficiency. 4. Severe liver disease. 5. History of regional enteritis, ulcerative colitis, or a history of antibiotic-associated colitis. 6. Evidence of any vulvovaginitis other than bacterial vaginosis. (e.g., candidiasis, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex). 7. Subjects with visible signs of HPV infection, i.e. visible warts. 8. Subject with another vaginal or vulvar condition, which would confound the interpretation of clinical response. 9. Subject will be under treatment during the study period for cervical intraepithelial neoplasia (CIN) or cervical carcinoma. 10. History of hypersensitivity to clindamycin, lincomycin, or any of the components of the vaginal creams. 11. Use within 2 weeks prior to baseline of 1) topical or systemic antibiotics or 2) topical or systemic antifungal. 12. Use of spermicides, tampons, douches, diaphragms, condoms within 48 hours of the baseline visit. 13. Concurrent use of systemic corticosteroids or systemic antibiotics. 14. Unwilling or unable to comply with the protocol requirements. 15. Subjects who have participated in an investigational drug study (i.e., subjects have been treated with an investigational drug) within 30 days prior to baseline will be excluded from study participation. Subjects who are participating in non-treatment studies such as observational studies or registry studies can be considered for inclusion. 16. Subjects who have been previously enrolled in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Both a Clinical and a Bacteriological Cure (Nugent Score <4), Evaluated at Visit 2 Test-of-cure (Study Day 22-30). | 22 to 30 days | Clinical Cure is defined as resolution of clinical signs and symptoms from entry visit as follows: 1. The original discharge characteristic of bacterial vaginosis has returned to a normal physiological vaginal discharge which varies in appearance and consistency depending on the menstrual cycle, 2. The whiff test is negative for any amine (fishy) odor, 3. The saline wet mount is negative for clue cells, 4. Vaginal fluid pH is \< 4.7, using pH paper that measures from 3.6 to 6.1. A Bacteriological cure is defined as a Nugent score \< 4. The system used a 0-4 scale (Nugent Scoring System 0-10 for Gram-Stained Vaginal Smears) for evaluation of vaginal flora, based on the weighted sum of the following 3 bacterial morphotypes scores calculated from slide examination under oil immersion field: 1. Lactobacillus: large gram positive rods, 2. Gardnerella / Bacteroides spp: Small gram variable coccobacilli/small Gram negative rods, 3. Mobiluncus spp.: thin, curved Gram variable rods |
Countries
Dominican Republic, Puerto Rico, United States
Participant flow
Pre-assignment details
The populations for this study included the Safety Population, the Per-Protocol (PP) Population, and the Modified Intent-to-treat (mITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Generic Clindamycin Phosphate Vaginal Cream 2% One single-dose, pre-filled, disposable applicator of investigational product was to be administered intravaginally at home. | 233 |
| Clindesse (Clindamycin Phosphate Vaginal Cream 2%) One single-dose, pre-filled, disposable applicator of investigational product was to be administered intravaginally at home. | 236 |
| Vehicle Cream One single-dose, pre-filled, disposable applicator of investigational product was to be administered intravaginally at home. | 122 |
| Total | 591 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 5 |
| Overall Study | Lost to Follow-up | 11 | 9 | 5 |
| Overall Study | Negative Nugent score at baseline | 6 | 2 | 2 |
| Overall Study | Other | 25 | 21 | 8 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Prohibited medication | 2 | 8 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 2 |
Baseline characteristics
| Characteristic | Generic Clindamycin Phosphate Vaginal Cream 2% | Total | Vehicle Cream | Clindesse (Clindamycin Phosphate Vaginal Cream 2%) |
|---|---|---|---|---|
| Age, Continuous | 34.5 years STANDARD_DEVIATION 9.66 | 35.1 years STANDARD_DEVIATION 9.98 | 35.1 years STANDARD_DEVIATION 10.17 | 35.8 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 120 Participants | 26 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 188 Participants | 471 Participants | 96 Participants | 187 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 | 4 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 16 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 94 Participants | 255 Participants | 55 Participants | 106 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 126 Participants | 304 Participants | 58 Participants | 120 Participants |
| Region of Enrollment United States | 233 participants | 591 participants | 122 participants | 236 participants |
| Sex: Female, Male Female | 233 Participants | 591 Participants | 122 Participants | 236 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 / 233 | 0 / 236 | 0 / 122 |
| other Total, other adverse events | 65 / 233 | 79 / 236 | 45 / 122 |
| serious Total, serious adverse events | 0 / 233 | 0 / 236 | 0 / 122 |
Outcome results
Primary
Number of Participants With Both a Clinical and a Bacteriological Cure (Nugent Score <4), Evaluated at Visit 2 Test-of-cure (Study Day 22-30).
Clinical Cure is defined as resolution of clinical signs and symptoms from entry visit as follows: 1. The original discharge characteristic of bacterial vaginosis has returned to a normal physiological vaginal discharge which varies in appearance and consistency depending on the menstrual cycle, 2. The whiff test is negative for any amine (fishy) odor, 3. The saline wet mount is negative for clue cells, 4. Vaginal fluid pH is \< 4.7, using pH paper that measures from 3.6 to 6.1. A Bacteriological cure is defined as a Nugent score \< 4. The system used a 0-4 scale (Nugent Scoring System 0-10 for Gram-Stained Vaginal Smears) for evaluation of vaginal flora, based on the weighted sum of the following 3 bacterial morphotypes scores calculated from slide examination under oil immersion field: 1. Lactobacillus: large gram positive rods, 2. Gardnerella / Bacteroides spp: Small gram variable coccobacilli/small Gram negative rods, 3. Mobiluncus spp.: thin, curved Gram variable rods
Time frame: 22 to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test Product | Number of Participants With Both a Clinical and a Bacteriological Cure (Nugent Score <4), Evaluated at Visit 2 Test-of-cure (Study Day 22-30). | 36 Participants |
| Reference Product | Number of Participants With Both a Clinical and a Bacteriological Cure (Nugent Score <4), Evaluated at Visit 2 Test-of-cure (Study Day 22-30). | 34 Participants |
| Placebo | Number of Participants With Both a Clinical and a Bacteriological Cure (Nugent Score <4), Evaluated at Visit 2 Test-of-cure (Study Day 22-30). | 9 Participants |