Safety Study of Lactobacillus Administered Vaginally to Healthy Women

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase I Study of the Safety of LACTIN-V Administered Vaginally to Healthy Women

Conditions
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Bacterial Vaginosis

Intervention / Treatment
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* Biological: Low dose LACTIN-V applicator
* Biological: Medium dose LACTIN-V applicator
* Biological: High dose LACTIN-V applicator
* Other: Low dose Placebo applicator
* Other: Medium dose Placebo
* Other: High dose Placebo applicator


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose LACTIN-V applicator<br>Low dose LACTIN-V applicator (150 mg LACTIN-V, 5.0 x 10^8 CFU), administered vaginally once a day for 5 consecutive days | Biological: Low dose LACTIN-V applicator<br>* Low dose LACTIN-V applicator (150 mg LACTIN-V, 5.0 x 10^8 CFU), administered vaginally once a day for 5 consecutive days<br>* Other names: Lactobacillus crispatus CTV-05;|
| Experimental: Medium dose LACTIN-V applicator<br>Medium dose LACTIN-V applicator (300 mg LACTIN-V, 1.0 x 10^9 CFU), administered vaginally once a day for 5 consecutive days | Biological: Medium dose LACTIN-V applicator<br>* Medium dose LACTIN-V applicator (300 mg LACTIN-V, 1.0 x 10^9 CFU), administered vaginally once a day for 5 consecutive days<br>* Other names: Lactobacillus crispatus CTV-05;|
| Experimental: High dose LACTIN-V applicator<br>High dose LACTIN-V applicator (600 mg LACTIN-V, 2.0 x 10^9 CFU), administered vaginally once a day for 5 consecutive days | Biological: High dose LACTIN-V applicator<br>* High dose LACTIN-V applicator (600 mg LACTIN-V, 2.0 x 10^9 CFU), administered vaginally once a day for 5 consecutive days<br>* Other names: Lactobacillus crispatus CTV-05;|
| Placebo Comparator: Low dose Placebo applicator<br>Low dose Placebo applicator (150 mg Placebo), administered vaginally once a day for 5 consecutive days | Other: Low dose Placebo applicator<br>* Low dose Placebo applicator (150 mg Placebo), administered vaginally once a day for 5 consecutive days<br>* Other names: Control substance;|
| Placebo Comparator: Medium dose Placebo applicator<br>Medium dose Placebo applicator (300 mg Placebo), administered vaginally once a day for 5 consecutive days | Other: Medium dose Placebo<br>* Medium dose Placebo applicator (300 mg Placebo), administered vaginally once a day for 5 consecutive days<br>* Other names: Control substance;|
| Placebo Comparator: High dose Placebo applicator<br>High dose Placebo applicator (600 mg Placebo), administered vaginally once a day for 5 consecutive days | Other: High dose Placebo applicator<br>* High dose Placebo applicator (600 mg Placebo), administered vaginally once a day for 5 consecutive days<br>* Other names: Control substance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 35 days | 
| 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. | 35 days |