Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048
Condition: Pharmacokinetics; Safety
Intervention: MK-2048 High Eudragit Vaginal Film; MK-2048 Low Eudragit Vaginal Film
Intervention description: 2" x 2" vaginal film containing 30 mg of MK-2048 and either 68.1 mg of ammonio methacrylate copolymer type B (Eudragit®); 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 37.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Vagina; Film; Extended Release

Summary:

      This is a proof of concept study to determine whether an extended release vaginal film can
      deliver drug for seven days. Two film formulations containing MK-2048 which differ by
      dissolution and spreadability attributes will be compared for safety and pharmacokinetic
      outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able and willing to provide written informed consent.

          -  Willing to use an effective method of birth control throughout the duration of the
             study. Examples of effective methods include: hormonal methods (other than NuvaRing®),
             intrauterine device, bilateral tubal ligation, same sex partner, partner with a
             vasectomy, abstinence (defined as no vaginal sex for one month prior to screening).

          -  Able and willing to provide adequate locator information

          -  HIV-uninfected based on testing performed by study staff at screening

          -  In general good health as determined by the site clinician

          -  Agree to be sexually abstinent, including use of sex toys, from visit 2 (Enrollment)
             until visit 7 (7 days after the biopsy visit) and 48 hours prior to all study visits.

          -  Agree to refrain from use of vaginal device or products (for example, lubricants,
             creams, suppositories) throughout participation in the study. Tampons may be used
             except between visit 5 (biopsy visit) and visit 7 (day 14).

          -  Willingness to undergo all study-related assessments and follow all study-related
             procedures

          -  At screening and enrollment, agrees not to participate in other research studies
             involving drugs, medical devices, or vaginal products while enrolled in this trial

          -  Participants over the age of 21 (inclusive) must have documentation of a satisfactory
             Pap within three years prior to Enrollment consistent with Grade 0 according to the
             Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November
             2007) to the Division of Acquired Immune Deficiency Syndrome Table for Grading Adult
             and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or satisfactory
             evaluation with no treatment required of grade 1 or higher Pap results. If no
             documentation of a Pap smear can be provided, a Pap smear will be collected at the
             screening visit.

        Exclusion Criteria:

          -  Menopause (as defined as amenorrhea for one year or more without an alternative
             etiology)

          -  Hysterectomy

          -  Participant report of any of the following:

               1. Known adverse reaction to any of the study products (ever)

               2. Non- therapeutic injection drug use in the 12 months prior to Screening

               3. Surgical procedure involving the pelvis in the 60 days prior to enrollment
                  (includes dilation and curettage or evacuation, and cryosurgery; does not include
                  cervical biopsy for evaluation of an abnormal pap smear)

               4. Participation in a drug, spermicide and/or microbicide study in the 30 days prior
                  to enrollment

               5. Currently pregnant or pregnancy within 42 days prior to enrollment

               6. Currently lactating

               7. Use of a diaphragm, NuvaRing®, or spermicide for contraception

          -  Urogenital infection or suspected infection within 7 days of enrollment including:
             symptomatic candidiasis, trichomonas vaginalis, and symptomatic bacterial vaginosis;
             or cervical infection, including N. gonorrhoeae, C. trachomatis, or mucopurulent
             cervicitis; syphilis; herpes simplex virus lesions, or other sores (Note: seropositive
             herpes simplex virus without active lesions will not be excluded); acute pelvic
             inflammatory disease; urinary tract infection; recent exposure to a partner with N.
             gonorrhoeae, C. trachomatis, Trichomonas, syphilis, or non-gonorrheal urethritis

          -  Antibiotic or antifungal therapy (vaginal or systemic) within 7 days of enrollment

          -  As determined by the primary investigator, has any significant uncontrolled active or
             chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal,
             psychiatric, endocrine *including poorly controlled diabetes), respiratory,
             immunologic disorder or infectious disease

          -  Menses-like bleeding at the time of the Enrollment visit* or expected menses-like
             bleeding within 14 days of the Enrollment visit (*Women who have vaginal bleeding at
             the scheduled Enrollment visit may return at a different date to be re-examined and
             possibly enrolled provided they are still within the screening window and meet all
             criteria.)

          -  Any condition that, in the opinion of the Investigator, would preclude provision of
             consent, make participation in the study unsafe, complicate interpretation of study
             outcome data, or otherwise interfere with achieving the study objectives