Bacterial Vaginosis
Conditions
Brief summary
The purpose of this study is to compare the safety, tolerability, and acceptability of LACTIN-V (Active Ingredient: Lactobacillus crispatus CTV-05) with a matching placebo at three doses using pre-filled vaginal applicators in healthy pre-menopausal women. The study hypothesis is that LACTIN-V will be safe, tolerable, and acceptable at each dose and will not differ significantly from the placebo controls.
Detailed description
The purpose of this study is to demonstrate that LACTIN-V is safe, well tolerated, and acceptable to healthy pre-menopausal women when administered vaginally using pre-filled applicators at doses of 150 mg (5.0 x 10\^8 CFU), 300 mg (1.0 x 10\^9 CFU), or 600 mg (2.0 x 10\^9 CFU) daily for 5 consecutive days as compared to placebo applicators containing 150 mg, 300 mg, or 600 mg of a matching placebo formulation without Lactobacillus crispatus CTV-05. Safety will be assessed by: * Incidence and severity of adverse events through assessing symptoms, physical examination findings, and signs of irritation involving the external genitalia, cervix or vagina, including disruption of the epithelium and blood vessels as seen on pelvic examination and colposcopy. * Laboratory parameters including urinalysis, a complete blood count (CBC) with differential, and chemistry panels to assess systemic effects of the study product. Tolerability will be assessed by: * The proportion of participants who discontinue study product use due to overt adverse events * The proportion of participants who complete the full dosing schedule Acceptability will be assessed by: \- Self-administered questionnaires and focus group discussions about acceptability of the study product
Interventions
BIOLOGICALLow dose LACTIN-V applicator
Low dose LACTIN-V applicator (150 mg LACTIN-V, 5.0 x 10\^8 CFU), administered vaginally once a day for 5 consecutive days
BIOLOGICALMedium dose LACTIN-V applicator
Medium dose LACTIN-V applicator (300 mg LACTIN-V, 1.0 x 10\^9 CFU), administered vaginally once a day for 5 consecutive days
BIOLOGICALHigh dose LACTIN-V applicator
High dose LACTIN-V applicator (600 mg LACTIN-V, 2.0 x 10\^9 CFU), administered vaginally once a day for 5 consecutive days
OTHERLow dose Placebo applicator
Low dose Placebo applicator (150 mg Placebo), administered vaginally once a day for 5 consecutive days
OTHERMedium dose Placebo
Medium dose Placebo applicator (300 mg Placebo), administered vaginally once a day for 5 consecutive days
OTHERHigh dose Placebo applicator
High dose Placebo applicator (600 mg Placebo), administered vaginally once a day for 5 consecutive days
Sponsors
University of California, San Francisco
Osel, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy pre-menopausal women 18- 40 years of age at date of screening. * Regular menstrual cycles (21-35 days) or amenorrheic for at least 3 months (long acting progestin contraceptives). * Normal Pap smear collected at the screening visit. * Previous sexual experience including vaginal intercourse. * Previous experience of gynecological examinations. * Currently in a mutually monogamous sexual relationship or not sexually active. * Agree to be sexually abstinent thoughout the trial. * Agree to abstain from the use of any other intravaginal product thoughout the trial * Agree to use an adequate method of birth control for the duration of the study to avoid pregnancy.
Exclusion criteria
* Urogenital infection at screening or within the 21 days prior to screening (UTI, bacterial vaginosis, Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum or Herpes simplex). * History of recurrent genital herpes. * Diagnosis of N. gonorrhoeae, C. trachomatis, T. pallidum or T. vaginalis on two or more occasions during the six months prior to screening. * Pregnancy or within 2 months of last pregnancy. * Lactation. * Antibiotic or antifungal therapy within 30 days of enrollment visit. * Concurrent investigational drug use within 30 days or 10 half-lives of the drug, of enrollment visit or during the study. * Menopause. * IUD insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser within the last 3 months. * Use of a NuvaRing® within 3 days of the screening visit or during the course of the study. * New (less than 3 months)long-acting treatments (e.g. depot formulation including medroxyprogesterone acetate (DMPA) form of hormonal birth control). - - Diabetes or other significant disease or acute illness. * Known HIV infection or positive HIV test at screening. * Immunosuppressive drug within 60 days. * Previous participation in a L. crispatus CTV-05 clinical study. * Colposcopic findings at the enrollment visit involving significant deep disruption of the epithelium. * Abnormal results for the pap smear at the screening visit. * Known allergy to any component of LACTIN-V, other significant drug allergy or to latex (condoms). * Known drug or alcohol abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of LACTIN-V in Healthy Pre-menopausal Women. | 35 days | Safety was measured by comparing the number of women experiencing adverse events of grade 3 or higher during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of LACTIN-V in a Pre-filled Applicator. | 35 days | Tolerability was measured as proportion of women remaining in the study, and NOT prematurely exiting the trial due to an adverse event. |
| Acceptability of LACTIN-V in Pre-filled Applicators | 35 days | Acceptability and overall satisfaction with the study product was measured using the response to the following question: I would use the product again with the following response options (strongly agree, agree, neutral, disagree, strongly disagree) Acceptability is reported as the number of women in each group who strongly agreed or agreed with the statement that they would use the product again. |
Countries
United States
Participant flow
Recruitment details
Between November 2007 and January 2008, 12 participants were recruited through advertising in health centers, educational institutions, community bulletin boards and online forums.
Pre-assignment details
All 12 enrolled participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Applicator Low dose LACTIN-V applicator (150 mg LACTIN-V, 5.0 x 10\^8 CFU) and Placebo applicator (150 mg Placebo), randomized 3:1 | 3 |
| Medium Dose Applicator Medium dose LACTIN-V applicator (300 mg LACTIN-V, 1.0 x 10\^9 CFU) and Placebo applicator (300 mg), randomized 3:1 | 3 |
| High Dose Applicator High dose LACTIN-V applicator (600 mg LACTIN-V, 2.0 x 10\^9 CFU) and Placebo applicator (600 mg Placebo), randomized 3:1 | 3 |
| Placebo Control Substance Low Dose Placebo control substance Low Dose contained a nutrient matrix of 150 mg per dose. | 1 |
| Placebo Control Substance Medium Dose Placebo control substance Medium Dose contained a nutrient matrix of 300 mg per dose. | 1 |
| Placebo Control Substance High Dose Placebo control substance High Dose contained a nutrient matrix of 600 mg per dose. | 1 |
| Total | 12 |
Baseline characteristics
| Characteristic | Medium Dose Applicator | High Dose Applicator | Placebo Control Substance Low Dose | Low Dose Applicator | Placebo Control Substance Medium Dose | Placebo Control Substance High Dose | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 12 Participants |
| Age, Continuous | 29.1 years STANDARD_DEVIATION 7 | 29.1 years STANDARD_DEVIATION 7 | 29.1 years STANDARD_DEVIATION 7 | 29.1 years STANDARD_DEVIATION 7 | 29.1 years STANDARD_DEVIATION 7 | 29.1 years STANDARD_DEVIATION 7 | 29.1 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 3 participants | 3 participants | 1 participants | 3 participants | 1 participants | 1 participants | 12 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 1 / 1 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 1 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Safety of LACTIN-V in Healthy Pre-menopausal Women.
Safety was measured by comparing the number of women experiencing adverse events of grade 3 or higher during the study.
Time frame: 35 days
Population: The analysis was per protocol. Number of participants for descriptive analysis only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Applicator | Safety of LACTIN-V in Healthy Pre-menopausal Women. | 0 participants |
| Medium Dose Applicator | Safety of LACTIN-V in Healthy Pre-menopausal Women. | 0 participants |
| High Dose Applicator | Safety of LACTIN-V in Healthy Pre-menopausal Women. | 0 participants |
| Placebo Control Substance Low Dose | Safety of LACTIN-V in Healthy Pre-menopausal Women. | 0 participants |
| Placebo Control Substance Medium Dose | Safety of LACTIN-V in Healthy Pre-menopausal Women. | 0 participants |
| Placebo Control Substance High Dose | Safety of LACTIN-V in Healthy Pre-menopausal Women. | 0 participants |
Secondary
Acceptability of LACTIN-V in Pre-filled Applicators
Acceptability and overall satisfaction with the study product was measured using the response to the following question: I would use the product again with the following response options (strongly agree, agree, neutral, disagree, strongly disagree) Acceptability is reported as the number of women in each group who strongly agreed or agreed with the statement that they would use the product again.
Time frame: 35 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Applicator | Acceptability of LACTIN-V in Pre-filled Applicators | 3 participants |
| Medium Dose Applicator | Acceptability of LACTIN-V in Pre-filled Applicators | 3 participants |
| High Dose Applicator | Acceptability of LACTIN-V in Pre-filled Applicators | 2 participants |
| Placebo Control Substance Low Dose | Acceptability of LACTIN-V in Pre-filled Applicators | 1 participants |
| Placebo Control Substance Medium Dose | Acceptability of LACTIN-V in Pre-filled Applicators | 0 participants |
| Placebo Control Substance High Dose | Acceptability of LACTIN-V in Pre-filled Applicators | 1 participants |
Secondary
Tolerability of LACTIN-V in a Pre-filled Applicator.
Tolerability was measured as proportion of women remaining in the study, and NOT prematurely exiting the trial due to an adverse event.
Time frame: 35 days
Population: Analysis per Protocol. Number of participants for descriptive analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Applicator | Tolerability of LACTIN-V in a Pre-filled Applicator. | 3 participants |
| Medium Dose Applicator | Tolerability of LACTIN-V in a Pre-filled Applicator. | 3 participants |
| High Dose Applicator | Tolerability of LACTIN-V in a Pre-filled Applicator. | 3 participants |
| Placebo Control Substance Low Dose | Tolerability of LACTIN-V in a Pre-filled Applicator. | 1 participants |
| Placebo Control Substance Medium Dose | Tolerability of LACTIN-V in a Pre-filled Applicator. | 1 participants |
| Placebo Control Substance High Dose | Tolerability of LACTIN-V in a Pre-filled Applicator. | 1 participants |