Bacterial Vaginosis (BV)
Conditions
Keywords
Bacterial vaginosis, Lactobacillus gasseri, Lactobacillus rhamnosus, Probiotics, Multicenter study
Brief summary
This is a mutilcenter, randomized, double-blind, Metronidazole controlled phase lIa clinical study to evaluate the safety and tolerability of dual - live lactobacilli-containing vaginal capsules for the treatment of Bacterial Vaginosis.
Detailed description
This phase of research adopts a mutilcenter, randomized, double-blind, Metronidazole controlled, dose-escalation, and multiple administration design. From May 2021 to July 2022, 60 subjects with BV were planned to be enrolled in multiple hospitals across the country. The test drug, a dual live bacteria formulation, was set up in three dose groups (1×10⁷ CFU/capsule, 1×10⁸ CFU/capsule, and 1×10⁹ CFU/capsule), with metronidazole tablets as the positive control in each group. Each group was planned to include 20 subjects, who were randomly assigned to the test group or the control group in a 3:1 ratio. A randomization table was generated using SAS 9.4, with each group randomized independently and enrolled in ascending order of dose according to the principle of dose escalation. Only after the current dose group completed the safety observation on Day 9 and confirmed to be safe and tolerable, could enrollment in the higher dose group be initiated.
Interventions
DRUGLive double combined lactobacillus capsule for vaginal use（1*10^7CFU/capsule）+Metronidazole placebo
Live double combined lactobacillus capsule for vaginal use（1\*10\^7CFU/capsule）+Metronidazole placebo, double-blind, double-dummy administration regimen
DRUGLow-dose group: Live double combined lactobacillus capsule placebo+Metronidazole
Low-dose group:Live double combined lactobacillus capsule placebo+Metronidazole, double-blind, double-dummy administration regimen.
DRUGLive double combined lactobacillus capsule for vaginal use（1*10^8CFU/capsule）+Metronidazole placebo
Live double combined lactobacillus capsule for vaginal use（1\*10\^8CFU/capsule）+Metronidazole placebo, double-blind, double-dummy administration regimen
DRUGMedium-dose group: Live double combined lactobacillus capsule placebo+Metronidazole
Medium-dose group: Live double combined lactobacillus capsule placebo+Metronidazole, double-blind, double-dummy administration regimen
DRUGLive double combined lactobacillus capsule for vaginal use（1*10^9CFU/capsule）+Metronidazole placebo
Live double combined lactobacillus capsule for vaginal use（1\*10\^9CFU/capsule）+Metronidazole placebo, double-blind, double-dummy administration regimen.
DRUGHigh-dose group: Live double combined lactobacillus capsule placebo+Metronidazole
High-dose group: Live double combined lactobacillus capsule placebo+Metronidazole, double-blind, double-dummy administration regimen.
Sponsors
Guangdong Longchuangji Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This trial employs a block randomization method, with each dose group being randomized separately. The randomization numbers and their corresponding treatment assignments are generated using SAS software (version 9.4). The randomization list (i.e., the blinding codes) is sealed in duplicate, with one copy stored by the sponsor and the other by the lead study unit. The randomization number serves as the blinded drug code for drug allocation. After subjects are screened and deemed eligible, researchers dispense the drugs sequentially in ascending order of the drug codes. On-site drug blinding is conducted by personnel from the statistical unit and the sponsor, who are otherwise unrelated to the trial. The predetermined randomization numbers (drug codes) are either written or affixed onto drug labels. A record of the blinding procedure is maintained and archived.
Intervention model description
This phase of the study will adopt a multicenter, randomized, double-blind, double-dummy, metronidazole-controlled, dose-escalation, and multiple-dose design. The investigational drug, a combination of Lactobacillus gasseri and Lactobacillus rhamnosus, will be administered in three dose groups: 1×10⁷ CFU/capsule, 1×10⁸ CFU/capsule, and 1×10⁹ CFU/capsule. Each dose group will use metronidazole tablets as the positive control. Each group is planned to enroll 20 subjects, who will be randomly assigned to either the investigational group or the control group in a 3:1 ratio. A randomization list will be generated using SAS 9.4, with separate randomization for each group. Subjects will be enrolled in ascending order of dose. Enrollment into the next higher dose group will only be initiated after the current dose group has completed the Day 9 safety observation and confirmed safety and tolerability.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Female, aged 18-50 years (inclusive), with prior sexual experience, willing to undergo vaginal drug administration, and agreeing to refrain from using intravaginal products (such as contraceptive creams, gels, foams, sponges, lubricants, douches, tampons, etc.) not specified in the study throughout the entire trial period. 2. Having a regular menstrual cycle (21-35 days). 3. Clinical diagnosis of bacterial vaginosis (BV), defined as meeting at least three of the Amsel criteria, with clue cells exceeding 20% of the total vaginal epithelial cells, and a Nugent score ≥ 7. 4. Able to understand and voluntarily sign the informed consent form.
Exclusion criteria
1. Individuals with a history of allergies or known hypersensitivity to any known component of the investigational product. 2. Known current diagnosis of pelvic inflammatory disease, cervicitis, or acute urogenital infection. 3. Diagnosis of vulvovaginal candidiasis (VVC), trichomonal vaginitis (TV), or aerobic vaginitis (AV, with a score ≥5). 4. Use of vaginal douching or other intravaginal treatments within 14 days prior to screening, or anticipated use during the trial period. 5. Known diagnosis of uterine fibroids, endometrial hyperplasia, or adenomyosis requiring intervention, as assessed by the investigator. 6. Patients who have used topical or systemic antimicrobial or antimycotic agents within 14 days prior to screening, or are anticipated to require such treatment during the trial period. 7. History of gynecological surgery within 2 months prior to screening. 8. Vaginal speculum examination at screening reveals significant vaginal mucosal damage (e.g., mucosal edema, congestion, ulceration, erosion). 9. History of major diseases affecting the cardiovascular, hepatic, renal, pulmonary, gastrointestinal, neurological, metabolic, urogenital, endocrine, or psychiatric systems, which in the investigator's judgment may compromise the subject's safety. 10. Any of the following laboratory findings at screening: Hemoglobin (HGB) \< 100 g/L; White blood cell (WBC) count \< 3.5 × 10⁹/L, or neutrophil count (NEUT) \< 1.5 × 10⁹/L; Platelet (PLT) count \< 80 × 10⁹/L; Serum creatinine (Cr) \> 1.5 × upper limit of normal (ULN); Blood urea nitrogen (BUN) \> 1.5 × ULN; Alanine aminotransferase (ALT) \> 1.5 × ULN; Aspartate aminotransferase (AST) \> 1.5 × ULN; Alkaline phosphatase (ALP) \> 1.5 × ULN; Total bilirubin (TBIL) \> 1.5 × ULN. 11. Participation in a clinical study within 3 months prior to screening. 12. Planning pregnancy within 2 months before screening to 6 months after the trial, or positive pregnancy test at screening. 13. Termination of pregnancy within 60 days prior to screening. 14. Lactating or postmenopausal women. 15. Physical conditions, concurrent surgeries, medications, or clinically significant abnormal laboratory findings that may affect the evaluation of the investigational product, as determined by the investigator. 16. Any other circumstances deemed unsuitable for participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent adverse events (Safety Evaluation) | Through study completion, an average of 30 days | A Treatment-emergent adverse event was defined as any adverse event occurring on or after the first use of the investigational product, regardless of causality. |
| Incidence of treatment-related adverse events (Safety Evaluation) | Through study completion, an average of 30 days | A treatment-related adverse event referred to any treatment-emergent adverse events with causal association to the treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cure rate of bacterial vaginosis in subjects | Day 12 to Day 16 | — |
| Recurrence rate of bacterial vaginosis in subjects | Day 25 to Day 31 | Recurrence rate at Day 25 to Day 31 |
Countries
China
Outcome results
None listed