Topical Metronidazole and Miconazole Co-formulated Vaginal Suppositories for Preventing Vaginal Infections in HIV-seronegative Women
Condition: Bacterial Vaginosis; Candidiasis; Trichomoniasis
MeSH terms: Candidiasis; Vaginosis, Bacterial; Trichomonas Infections; Vaginal Diseases
Intervention: Neo-Penotran® Forte (active ingredient Metronidazole & Miconazole Nitrate); Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Metronidazole; Miconazole; Clotrimazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 234.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Bacterial vaginosis, metronidazole, miconazole, vulvovaginal candidiasis, trichomonas vaginalis, women, Kenya

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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:

               1. BV: Microscopic criteria (Nugent's score greater than or equal to 7)

               2. VVC: Fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet
                  mount plus a positive culture showing yeast on Sabouraud's agar.

               3. 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.

        Exclusion Criteria:

          -  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

               1. Porphyria

               2. Epilepsy

               3. Serious liver disease or signs and symptoms consistent with serious liver disease
                  including jaundice, ascites, esophageal varices, encephalopathy, and bleeding
                  disorders.

               4. 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)

               1. Warfarin

               2. Phenytoin

               3. Phenobarbital

               4. Disulfiram

               5. Cimetidine

               6. Lithium

               7. Astemizole

               8. Terfenadine

          -  Current use of oral or intravaginal antifungal medication.

          -  Current use of oral or intravaginal metronidazole, tinidazole, or clindamycin.

          -  Current use of latex diaphragm.

          -  As determined by the investigator, a medical condition or situation exists such that
             study participation would not be advisable.