Efficacy and Safety Study of Rifaximin Vaginal Tablets in Bacterial Vaginosis (VARIANT)
Primary Purpose
BACTERIAL VAGINOSIS
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RIFAXIMIN VAGINAL TABLET 25 MG
RIFAXIMIN VAGINAL TABLET 100 MG
PLACEBO VAGINAL TABLET
METROGEL VAGINAL
Sponsored by
About this trial
This is an interventional treatment trial for BACTERIAL VAGINOSIS
Eligibility Criteria
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
Sites / Locations
- College of Medicine Drexel University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Active Comparator
Arm Label
RIFAXIMIN VAGINAL TABLET 25 MG
RIFAXIMIN VAGINAL TABLET 100 MG
PLACEBO VAGINAL TABLET
METROGEL VAGINAL
Arm Description
RIFAXIMIN VAGINAL TABLET 25 MG ADMINISTERED ONCE A DAY FOR 5 DAYS
RIFAXIMIN VAGINAL TABLET 100 MG ADMINISTERED ONCE A DAY FOR 5 DAYS
PLACEBO VAGINAL TABLET ADMINISTERED ONCE A DAY FOR 5 DAYS
METROGEL VAGINAL ADMINISTERED ONCE A DAY FOR 5 DAYS
Outcomes
Primary Outcome Measures
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%
Secondary Outcome Measures
BACTERIOLOGICAL CURE OF BACTERIAL VAGINOSIS
GRAM STAIN NUGENT SCORE <4
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)
MAINTENANCE OF CLINICAL CURE OF BACTERIAL VAGINOSIS
AMSEL'S CRITERIA (RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA)
MAINTENANCE OF BACTERIOLOGICAL CURE OF BACTERIAL VAGINOSIS
NUGENT SCORE <4
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)
NUMBER, INTENSITY AND TYPE OF ADVERSE EVENTS
The incidence of adverse events to be summarized by body system and MedDRA preferred term.
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)
LOCAL SUBJECTIVE TOLERABILITY
Grade (from 0 to 4) of vaginal itching, pain and burning
Full Information
NCT ID
NCT02376972
First Posted
February 19, 2015
Last Updated
October 7, 2016
Sponsor
Alfasigma S.p.A.
Collaborators
Parexel
1. Study Identification
Unique Protocol Identification Number
NCT02376972
Brief Title
Efficacy and Safety Study of Rifaximin Vaginal Tablets in Bacterial Vaginosis
Acronym
VARIANT
Official Title
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Rifaximin Vaginal Tablets in the Treatment of Bacterial Vaginosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Terminated
Why Stopped
According to the Recommendation of the Indipendent Data Monitoring Committee
Study Start Date
April 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alfasigma S.p.A.
Collaborators
Parexel
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
BACTERIAL VAGINOSIS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
392 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RIFAXIMIN VAGINAL TABLET 25 MG
Arm Type
Experimental
Arm Description
RIFAXIMIN VAGINAL TABLET 25 MG ADMINISTERED ONCE A DAY FOR 5 DAYS
Arm Title
RIFAXIMIN VAGINAL TABLET 100 MG
Arm Type
Experimental
Arm Description
RIFAXIMIN VAGINAL TABLET 100 MG ADMINISTERED ONCE A DAY FOR 5 DAYS
Arm Title
PLACEBO VAGINAL TABLET
Arm Type
Placebo Comparator
Arm Description
PLACEBO VAGINAL TABLET ADMINISTERED ONCE A DAY FOR 5 DAYS
Arm Title
METROGEL VAGINAL
Arm Type
Active Comparator
Arm Description
METROGEL VAGINAL ADMINISTERED ONCE A DAY FOR 5 DAYS
Intervention Type
Drug
Intervention Name(s)
RIFAXIMIN VAGINAL TABLET 25 MG
Intervention Description
RIFAXIMIN VAGINAL TABLET 25 MG O.D./5 DAYS INTRAVAGINALLY
Intervention Type
Drug
Intervention Name(s)
RIFAXIMIN VAGINAL TABLET 100 MG
Intervention Description
RIFAXIMIN VAGINAL TABLET 100 MG O.D./5 DAYS INTRAVAGINALLY
Intervention Type
Drug
Intervention Name(s)
PLACEBO VAGINAL TABLET
Intervention Description
PLACEBO VAGINAL TABLET O.D./5 DAYS INTRAVAGINALLY
Intervention Type
Drug
Intervention Name(s)
METROGEL VAGINAL
Intervention Description
METROGEL VAGINAL O.D./5 DAYS INTRAVAGINALLY
Primary Outcome Measure Information:
Title
CLINICAL CURE OF BACTERIAL VAGINOSIS
Description
RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA, I.E. NORMAL PHYSIOLOGICAL DISCHARGE, NEGATIVE "WHIFF TEST", CLUE CELLS >20%
Time Frame
Day 22-30
Secondary Outcome Measure Information:
Title
BACTERIOLOGICAL CURE OF BACTERIAL VAGINOSIS
Description
GRAM STAIN NUGENT SCORE <4
Time Frame
Day 22-30
Title
THERAPEUTIC CURE OF BACTERIAL VAGINOSIS
Description
AMSEL'S CRITERIA AND GRAM STAIN NUGENT (RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA AND NUGENT SCORE <4)
Time Frame
Day 22-30
Title
MAINTENANCE OF CLINICAL CURE OF BACTERIAL VAGINOSIS
Description
AMSEL'S CRITERIA (RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA)
Time Frame
Day 61-70
Title
MAINTENANCE OF BACTERIOLOGICAL CURE OF BACTERIAL VAGINOSIS
Description
NUGENT SCORE <4
Time Frame
Day 61-70
Title
MAINTENANCE OF THERAPEUTIC CURE OF BACTERIAL VAGINOSIS
Description
AMSEL'S CRITERIA AND NUGENT SCORE (MAINTENANCE OF RESOLUTION OF 3 OUT OF 4 AMSEL'S CRITERIA AND NUGENT SCORE <4)
Time Frame
60-69 DAYS AFTER THE FIRST DAY OF TREATMENT
Title
NUMBER, INTENSITY AND TYPE OF ADVERSE EVENTS
Description
The incidence of adverse events to be summarized by body system and MedDRA preferred term.
Time Frame
Up to Day 70
Title
LOCAL OBJECTIVE TOLERABILITY
Description
Vaginal mucosa status in terms of erythema (score 0 to 3), edema (score 0 to 3), pethechial hemorrhages (absence/presence), ulcers (absence/presence)
Time Frame
Day 22-30
Title
LOCAL SUBJECTIVE TOLERABILITY
Description
Grade (from 0 to 4) of vaginal itching, pain and burning
Time Frame
Day 1 to Day 5
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raffaella Tacchi, MD
Organizational Affiliation
Alfasigma S.p.A.
Official's Role
Study Director
Facility Information:
Facility Name
College of Medicine Drexel University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191012-1192
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Efficacy and Safety Study of Rifaximin Vaginal Tablets in Bacterial Vaginosis
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