Efficacy and Safety Study of Rifaximin Vaginal Tablets in Bacterial Vaginosis

Study Overview
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Brief Summary
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THE STUDY HAS BEEN DESIGNED TO COMPARE THE EFFICACY OF TWO DOSES (25 MG AND 100 MG) OF RIFAXIMIN VAGINAL TABLETS VERSUS PLACEBO IN SUBJECTS WITH BACTERIAL VAGINOSIS

Detailed Description
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THIS IS A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY PLANNING TO ENROL 626 SUBJECTS AFFECTED BY BACTERIAL VAGINOSIS. PRIMARY ENDPOINT: TO COMPARE THE EFFICACY OF TWO DOSES (25 MG AND 100 MG) OF RIFAXIMIN VAGINAL TABLETS VERSUS PLACEBO IN SUBJECTS WITH BACTERIAL VAGINOSIS SECONDARY ENDPOINT: TO COMPARE THE EFFICACY OF TWO DOSES (25 MG AND 100 MG) OF RIFAXIMIN VAGINAL TABLETS VERSUS METROGEL VAGINAL IN SUBJECTS WITH BACTERIAL VAGINOSIS.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Rifaximin Vaginal Tablets in the Treatment of Bacterial Vaginosis

Conditions
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BACTERIAL VAGINOSIS

Intervention / Treatment
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* Drug: RIFAXIMIN VAGINAL TABLET 25 MG
* Drug: RIFAXIMIN VAGINAL TABLET 100 MG
* Drug: PLACEBO VAGINAL TABLET
* Drug: METROGEL VAGINAL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of bacterial vaginosis with Amsel's criteria (4 out of 4 fulfilled criteria): Off white (milky or gray), thin, homogeneous, adherent vaginal discharge pH >4.5 Positive whiff test Presence of clue cells ≥20% Bacteriological diagnosis of bacterial vaginosis with Gram stain Nugent score ≥ 4 (patients may be enrolled/randomized without this result) Post-menarchal, pre-menopausal female patient Non-pregnant (negative urine pregnancy test at Entry Visit/V1) nor breast-feeding patient Patient aged between 18 50 years, inclusively Patient who is willing to be asked questions about personal medical health and sexual history Patient capable of and willing to conform to the study protocol Patient who have been thoroughly informed of the aim of the study and the study procedures and who provided signed and dated written informed consent form Patient who agrees to abstain from intercourse during the 5 day treatment period Patient who agrees also to abstain from intercourse 3 days before the scheduled visits of follow-up Patient who agrees to abstain from the use of any other intravaginal product (i.e., douching, feminine deodorants sprays, tampons, spermicides, gels, foams, vaginal birth control ring and diaphragms) during the entire study period Patient who agrees to use an adequate method of birth control for the duration of the study to avoid pregnancy. Acceptable methods include a history of bilateral tubal ligation, male partner with a vasectomy, a hormonal contraceptive [oral, patch, injectable or implantable (excluding intrauterine implantable devices [IUD], intrauterine system [IUS] and vaginal rings), or abstinence Patient who agrees to abstain from alcohol ingestion during the 5-day treatment period and for 1 day afterward Exclusion Criteria: Virginity Patient with other infectious causes of vulvovaginitis (e.g., candidiasis, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, active Herpes simplex lesions, or Human Papilloma Virus lesions); patients may be enrolled/randomized without these results) Other vulvovaginal or cervical conditions, abnormalities or disorders confounding the interpretation of clinical response (including total hysterectomy) Symptoms suggestive of pelvic inflammatory disease Patient with intra uterine device (IUD), intrauterine system (IUS), or vaginal ring as contraceptive method Patient with severe hepatic insufficiency (Child C) Patient with severe cardiac insufficiency (NYHA - New York Heart Association classes 3 - 4) Patient who will be being evaluated, including colposcopy and cervical biopsies, or being treated during the study period, for abnormal Pap test or cervical carcinoma. To note that if the Pap test will be performed at baseline, the result will be known after the randomization visit: patients may be enrolled without this result Any condition or circumstance that would prevent completion of the study or interfere with analysis of study results, including a history of drug or alcohol abuse, mental illness or non-compliance with treatments or visits, immunological (including HIV infection), hematological or neoplastic disease (including all cervical neoplastic diseases) Cervical cryotherapy, loop electrosurgical excision (LEEP), cervical laser, or any other ablative or excisional cervical procedures within the last 3 months Vaginal laser within the last 3 months Patient with clinically relevant pathological laboratory values Known hypersensitivity to rifaximin Known hypersensitivity to excipients present in rifaximin, placebo or metronidazole formulations Known hypersensitivity to metronidazole, either orally or topically administered, or any forms of parabens Concurrent anticoagulant therapy with coumadin or warfarin Menstruating or anticipated menstruation/withdrawal bleed at Entry Visit/V1 and during the drug administration Patient who received antifungal or antimicrobial therapy (systemic or intravaginal) within 14 days of randomization Patient who have participated in another clinical trial or have taken an investigational drug within the last 4 weeks prior screening Patient who has taken disulfuram within the last 14 days Withdrawal of informed consent Patient previously randomized in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIFAXIMIN VAGINAL TABLET 25 MG<br>RIFAXIMIN VAGINAL TABLET 25 MG ADMINISTERED ONCE A DAY FOR 5 DAYS | Drug: RIFAXIMIN VAGINAL TABLET 25 MG<br>* RIFAXIMIN VAGINAL TABLET 25 MG O.D./5 DAYS INTRAVAGINALLY<br>|
| Experimental: RIFAXIMIN VAGINAL TABLET 100 MG<br>RIFAXIMIN VAGINAL TABLET 100 MG ADMINISTERED ONCE A DAY FOR 5 DAYS | Drug: RIFAXIMIN VAGINAL TABLET 100 MG<br>* RIFAXIMIN VAGINAL TABLET 100 MG O.D./5 DAYS INTRAVAGINALLY<br>|
| Placebo Comparator: PLACEBO VAGINAL TABLET<br>PLACEBO VAGINAL TABLET ADMINISTERED ONCE A DAY FOR 5 DAYS | Drug: PLACEBO VAGINAL TABLET<br>* PLACEBO VAGINAL TABLET O.D./5 DAYS INTRAVAGINALLY<br>|
| Active Comparator: METROGEL VAGINAL<br>METROGEL VAGINAL ADMINISTERED ONCE A DAY FOR 5 DAYS | Drug: METROGEL VAGINAL<br>* METROGEL VAGINAL O.D./5 DAYS INTRAVAGINALLY<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLINICAL CURE OF BACTERIAL VAGINOSIS | RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA, I.E. NORMAL PHYSIOLOGICAL DISCHARGE, NEGATIVE WHIFF TEST, CLUE CELLS >20% | Day 22-30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BACTERIOLOGICAL CURE OF BACTERIAL VAGINOSIS | GRAM STAIN NUGENT SCORE <4 | Day 22-30 | 
| THERAPEUTIC CURE OF BACTERIAL VAGINOSIS | AMSEL'S CRITERIA AND GRAM STAIN NUGENT (RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA AND NUGENT SCORE <4) | Day 22-30 | 
| MAINTENANCE OF CLINICAL CURE OF BACTERIAL VAGINOSIS | AMSEL'S CRITERIA (RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA) | Day 61-70 | 
| MAINTENANCE OF BACTERIOLOGICAL CURE OF BACTERIAL VAGINOSIS | NUGENT SCORE <4 | Day 61-70 | 
| MAINTENANCE OF THERAPEUTIC CURE OF BACTERIAL VAGINOSIS | AMSEL'S CRITERIA AND NUGENT SCORE (MAINTENANCE OF RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA AND NUGENT SCORE <4) | 60-69 DAYS AFTER THE FIRST DAY OF TREATMENT | 
| NUMBER, INTENSITY AND TYPE OF ADVERSE EVENTS | The incidence of adverse events to be summarized by body system and MedDRA preferred term. | Up to Day 70 | 
| LOCAL OBJECTIVE TOLERABILITY | Vaginal mucosa status in terms of erythema (score 0 to 3), edema (score 0 to 3), pethechial hemorrhages (absence/presence), ulcers (absence/presence) | Day 22-30 | 
| LOCAL SUBJECTIVE TOLERABILITY | Grade (from 0 to 4) of vaginal itching, pain and burning | Day 1 to Day 5 |