Quantification of Estradiol's Impact on Nucleotides in Cellular Populations of the Lower GI Tract
Condition: HIV/AIDS
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Tenofovir 300Mg Oral Tablet; Emtricitabine 200 MG
Intervention description: Once daily dose of the combo tab x 5 days pre-sampling; Once daily dose of the combo tab x 5 days pre-sampling
Intervention MeSH terms: Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: Female
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Purpose: To Assess the impact of high and low in vivo estradiol exposure on PrEP
      (Pre-exposure prophylaxis) nucleotide concentrations in different cellular populations of the
      lower GI (gastrointestinal) tract and to quantify the relationship between estradiol,
      progesterone, and testosterone on PrEP nucleotide concentrations in rectal and peripheral
      blood mononuclear cells. As well as the relationship between estradiol, progesterone, and
      testosterone on PrEP concentrations in plasma.

      Participants: Healthy, cisgender female, volunteers, aged 18-49 inclusive on the date of
      screening with an intact gastrointestinal system and regular menstrual cycle.

      Procedures (methods): Participants will take a single daily dose of study drug for five days
      before each sampling visit. The visits will be scheduled during the early follicular phase of
      the menstrual cycle (approximately days 2-5 after the first day of menses, Visit 1) when
      estradiol is predicted to be the lowest and the late follicular phase (approximately days
      12-15 after the first day of menses, Visit 2) when estradiol is predicted to be highest.
      Samples of blood, rectal cells, and rectal tissue will be collected at both Visits 1 and 2.
      All participants will complete a follow-up safety visit within 14 days of completing study
      sampling.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy cisgender pre-menopausal female participants between the ages of 18 and 49
             years, inclusive on the date of screening (Healthy is defined as no irregular
             menstrual cycles or clinically relevant abnormalities identified by a detailed medical
             history, full physical examination, including blood pressure and pulse rate
             measurement, and clinical laboratory tests.

          -  Regular menstrual cycles defined as at least 1 day of menses occurring every 21-35
             days)

          -  Estimated calculated creatinine clearance (eCcr) of at least 60 mL/min by the
             Cockcroft-Gault formula where: eCcr (female) in mL/min = [(140 - age in years) x
             (weight in kg) x 0.85] / (72x serum creatinine in mg/dL).

          -  Negative serum pregnancy test at screening

          -  All participants should be using at least one of the following methods of
             contraception* from the screening visit through 72 hours prior to inpatient admission
             (at which time the women will be asked to remain abstinent until after their follow-up
             visit):

               1. Non continuous systemic hormonal contraceptives that permit intermittent
                  menstruation

               2. IUD (non-hormonal intrauterine device) placed at least 1 month prior to study
                  enrollment

               3. Bilateral tubal ligation (Sterilization)

               4. Vasectomized male partners

               5. Condom + Spermicide

               6. *Unless engaged in sexual activity with female only sex partners or abstinent for
                  at least 3 months prior with no intention of becoming sexually active during the
                  study period. Any history of recent or present concomitant male sex partners will
                  be addressed and ruled out in the context of screening participants for
                  eligibility for the protocol

          -  Evidence of a personally signed and dated informed consent document indicating that
             the subject has been informed of all pertinent aspects of the trial.

          -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
             and other trial procedures.

          -  Subject must be willing to abstain from sexual intercourse, and all and intrarectal
             objects and products for at least 72 hours prior to Sampling #1 until study
             completion.

          -  Subject must be HIV-1 and Hepatitis B and C negative as documented on screening labs.

          -  Subject must not be actively involved in the conception process and must be
             non-lactating.

          -  Subject must be able to swallow pills and have no allergies to any component of the
             study product

        Exclusion Criteria:

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
             allergic disease (including documented drug allergies, but excluding untreated,
             asymptomatic, seasonal allergies at time of dosing).

          -  Participants with a history of hysterectomy

          -  Participants who are pregnant, possibly pregnant or lactating

          -  History of febrile illness within five days prior to first dose.

          -  Any condition possibly affecting drug absorption (eg, gastrectomy or other significant
             alterations of the gastrointestinal tract)

          -  A positive urine drug screen.

          -  An untreated-positive test for syphilis, gonorrhea, or Chlamydia at screening.

          -  Any clinically relevant laboratory chemistry or hematology result Grade 2 or greater
             according to the Division of AIDS Laboratory Grading Tables

          -  Treatment with an investigational drug within 4 months preceding the first dose of
             study product.

          -  History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150
             mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week.

          -  Participation in a clinical trial involving rectal biopsies within 6 months preceding
             the first dose of trial medication.

          -  Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.

          -  Any condition which, in the opinion of the investigator, is likely to interfere with
             follow-up or ability to take the study medication appropriately.

          -  Unwilling or unable to comply with the dietary and concomitant drug restrictions in
             regard to study drug administration as outlined in the study procedures and prohibited
             medications sections.

          -  Women utilizing continuous hormonal contraception options such as Seasonique,
             injectables, implants, and hormonal IUDs