Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories for Preventing Vaginal Infections in HIV-seronegative Women

NCT01230814 | Completed Phase 2 Results

• 2 other identifiers: 09-0070DMID STI CTG 09-0070 PVI
• Study Type: interventional
• Target: 234
• Locations: 2 countries
• Sites: 4

Brief Summary

This research study is about vaginal infections such as bacterial vaginosis, yeast infections, and trichomoniasis. Usually, these infections can be treated with medication, but sometimes they come back after treatment. Researchers want to know if using vaginal suppositories can decrease the risk of vaginal infections. Participants will include 234 women who are sexually active (greater than or equal to 4 episodes of sex with men during the past month), HIV-negative, 18 to 45 years old, with bacterial infection \[vaginosis and/or vulvovaginal candidiasis (VVC) and/or Trichomonas vaginalis\] detected by laboratory testing at a screening visit. Women will receive vaginal suppositories containing drug or inactive ingredients (placebo). Participation in the study will be about 12 months. Study procedures include: urine and blood tests, physical exams, and questionnaires.

Conditions

Bacterial Vaginosis; Candidiasis; Trichomoniasis

Keywords

Bacterial vaginosis, metronidazole, miconazole, vulvovaginal candidiasis, trichomonas vaginalis, women, Kenya

Outcome Measures

Primary Outcomes (2)

• Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Vulvovaginal Candidiasis (VVC).

  Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for VVC based on the presence of fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud's agar.

  Months 2, 4, 6, 8, 10, and 12.

• Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing Bacterial Vaginosis (BV).

  Percentage of follow-up visits (Months 2, 4, 6, 8, 10, 12) positive for BV as determined by applying standard microscopic scoring criteria (Nugent's criteria) to vaginal Gram stained slides. BV is diagnosed when the score is greater than or equal to 7.

  Months 2, 4, 6, 8, 10, and 12.

Secondary Outcomes (2)

• Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Placebo for Preventing Any Vaginal Infection (a Combined Endpoint Including BV, VVC, and Trichomonas Vaginalis Infection).

  Months 2, 4, 6, 8, 10, and 12.

• Efficacy of Monthly Periodic Presumptive Treatment (PPT) Using Metronidazole With Miconazole Intravaginal Suppositories Versus Matching Placebo Nightly for Five Nights Each Month for Preventing BV by Clinical Criteria (Amsel's Criteria).

  Months 2, 4, 6, 8, 10, and 12.

Study Arms (2)

Arm 1

EXPERIMENTAL

Intravaginal metronidazole 750 mg plus miconazole 200 mg (co-formulated suppositories) nightly for 5 consecutive nights each month; 117 Subjects.

Drug: Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate)

Arm 2

PLACEBO COMPARATOR

Placebo suppositories nightly for five consecutive nights each month; 117 Subjects.

Drug: Placebo

Interventions

Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate) DRUG

Neo-Penotran® Forte (active ingredient Metronidazole \& Miconazole Nitrate), co-formulated vaginal suppositories containing metronidazole 750 mg with miconazole 200 mg and excipients (Witepsol S 55). Witepsol S 55 is a hard fat suppository base. Such bases consist mainly of triglyceride esters of the higher saturated fatty acids along with varying proportions of mono- and diglycerides. 117 subjects receive nightly for 5 consecutive night each month.

Arm 1

Placebo DRUG

Placebo vaginal suppositories, identical in appearance to the active product; contains Witepsol S 55, Titanium Dioxide and D+C yellow #10 with no metronidazole or miconazole.117 subjects receive nightly for 5 consecutive nights each month.

Arm 2

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent obtained and informed consent form (ICF) signed.
• Female, aged 18-45 years.
• Sexually active with greater than or equal to 4 episodes of sex with a male partner during the past month.
• Human immunodeficiency virus (HIV)-seronegative on both HIV tests in parallel screening.
• Presence of bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or T. vaginalis infection at screening:
• BV: Microscopic criteria (Nugent's score greater than or equal to 7)
• VVC: Fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud's agar.
• T. vaginalis infection: Identification of motile trichomonads on vaginal saline wet preparation.
• Able and willing to comply with study visit schedule and procedures during the 12-month period of follow-up.
• Able and willing to abstain from sex or to use non-latex condoms (provided) for 24 hours following insertion of each vaginal suppository.
• Willing to abstain from alcohol during, and for 48 hours after, treatment.
• Plan to remain in study area for the next year.
• Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study.

You may not qualify if:

• Currently pregnant (positive urine Beta-Human Chorionic Gonadotropin (hCG) or planning to conceive during the next 12 months (by self-report).
• Currently breastfeeding.
• Within first 3 months post-partum.
• Current menstruation - women who are currently menstruating may be enrolled following the completion of menses.
• History of 4 or more episodes of treatment for any vaginal infection in the past 12 months. This would be a cumulative total, including any treatment for bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or Trichomonas vaginalis (TV) and/or syndromic.
• History of medical condition that would contraindicate use of the study product
• Porphyria
• Epilepsy
• Serious liver disease or signs and symptoms consistent with serious liver disease including jaundice, ascites, esophageal varices, encephalopathy, and bleeding disorders.
• Renal failure
• History of adverse reaction to the study medications (intravaginal metronidazole or miconazole).
• Current use of medication that may interact with the study drug (due to vaginal absorption of study drug)
• Warfarin
• Phenytoin
• Phenobarbital

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

University of Alabama at Birmingham Medical Center

Birmingham, Alabama, 35294-0007, United States

Location

Women's Health Project - Ganjoni Municipal Clinic

Mombasa, Coast, Kenya

Location

University of Nairobi - Center for STD/HIV Research & Training

Nairobi, Nairobi County, Kenya

Location

University of Nairobi - Kenya AIDS Vaccine Initiative

Nairobi, Nairobi County, Kenya

Location

MeSH Terms

Conditions

Vaginosis, Bacterial; Candidiasis; Trichomonas Infections; Candidiasis, Vulvovaginal

Interventions

Miconazole

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Mycoses; Protozoan Infections; Parasitic Diseases; Vulvovaginitis; Vulvitis; Vulvar Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Shelly Lensing, MS
• Organization: University of Arkansas for Medical Sciences

sylensing@uams.edu

501-686-8203

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2010
• First Posted: October 29, 2010
• Study Start: April 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: October 6, 2014
• Results First Posted: September 26, 2014

Record last verified: 2014-09

Locations

KE (3); US (1)