Clinical trial: Phase I One-month Safety, PK, PD, and Acceptability Study of IVR Releasing TFV and LNG or TFV Alone (NCT02235662)

Eligibility criteria:
Inclusion Criteria:

          -  Age 18-45 years, inclusive

          -  General good health (by volunteer history and per investigator discretion) without any
             clinically significant systemic disease (including, but not limited to significant
             liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease,
             osteoporosis or bone disease, and diabetes)

          -  Currently having regular menstrual cycles of 26-35 days by participant report

          -  History of Pap smears and follow-up consistent with standard medical practice as
             outlined in the study manual or willing to undergo a Pap smear

          -  Protected from pregnancy by one of the following: 1) Sterilization of either partner.
             Note: Women protected from pregnancy by sterilization of either partner must abstain
             from vaginal intercourse from 48 hours prior to Visit 3 until the sixth day after the
             last study visit; or 2) Willing to abstain from vaginal intercourse from Visit 1 until
             the sixth day after the last study visit.

          -  Willing to abstain from any other vaginal activity and the use of vaginal product
             other than the study product including tampons, spermicides, lubricants, and douches
             starting 48 hours before Visit 3 until the sixth day after the last study visit

          -  Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to
             easy colposcopy and genital tract sample collection

          -  Negative urine pregnancy test

          -  P4 ≥3 ng/ml

          -  Willing to give voluntary consent, sign an informed consent form and comply with study
             procedures as required by the protocol

        Exclusion Criteria:

          -  History of hysterectomy

          -  Currently pregnant or within two calendar months from the last pregnancy outcome.
             Note: If recently pregnant must have had at least two spontaneous menses since
             pregnancy outcome.

          -  Use of any hormonal contraceptive method in the last 3 months (oral, transdermal,
             transvaginal, implant, or hormonal intrauterine contraceptive device)

          -  Injection of Depo-Provera in the last 10 months

          -  Use of copper intrauterine device (IUD) after Visit 1

          -  Currently breastfeeding or having breastfed an infant in the last two months, or
             planning to breastfeed during the course of the study

          -  History of sensitivity/allergy to any component of: TFV 1% gel, topical anesthetic, or
             allergy to both silver nitrate and Monsel's solution.

          -  Contraindication to LNG

          -  In the last six months, diagnosed with or treated for any sexually transmitted
             infection (STI) or pelvic inflammatory disease. Note: Women with a history of genital
             herpes or condylomata who have been asymptomatic for at least six months may be
             considered for eligibility.

          -  Nugent score greater than or equal to 7 or symptomatic bacterial vaginosis (BV) as
             defined by Amsel's criteria

          -  Positive test for Trichomonas vaginalis, Neisseria gonorrhea (GC), Chlamydia
             trachomatis (CT), HIV, or Hepatitis B surface antigen (HBsAg)

          -  Known bleeding disorder that could lead to prolonged or continuous bleeding with
             biopsy

          -  Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting, etc.)

          -  Known current drug or alcohol abuse which could impact study compliance

          -  Grade 2 or higher laboratory abnormality, per the August 2009 update of the Division
             of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for
             Grading the Severity of Adverse Events, or clinically significant laboratory
             abnormality as determined by the clinician

          -  Systemic use in the last two weeks or anticipated use during the study of any of the
             following: corticosteroids, antibiotics, anticoagulants or other drugs known to
             prolong bleeding and/or clotting, antifungals, antivirals (e.g., acyclovir or
             valacyclovir) or antiretrovirals (e.g., Viread, Atripla®, Emtriva®, Complera®). Note:
             Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) except for
             treatment of dysmenorrhea during menses. Participants may use Tylenol® on an as-needed
             but not daily basis during the study

          -  Participation in any other investigational trial (device, drug, or vaginal trial)
             within the last 30 days or planned participation in any other investigational trial
             during the study

          -  History of gynecological procedures (including genital piercing) on the external
             genitalia, vagina or cervix within the last 14 days

          -  Abnormal finding on laboratory or physical examination or a social or medical
             condition which, in the opinion of the investigator, would make participation in the
             study unsafe or would complicate interpretation of data
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 45 Years

Patient description (medical language): A 23-year-old female has prolonged oral bleeding immediately after a tooth extraction.  Despite several interventions, the bleeding persists for hours and stops only after desmopressin (DDAVP) administration.  The patient has heavy menstrual cycles each month.  She has no other medical problems and takes no medications.  Her mother and grandmother have also had excessive bleeding during menstrual period.  Review of systems is positive for mild bruising on his legs. Laboratory findings reveal a normal platelet count and an abnormal ristocetin cofactor assay, as well as CB <= 0.30 IU/mL and FVIII:C <= 0.40 IU/mL.

Patient description (patient's own words): I'm a 23 woman and I went to the ER because of non-stop bleeding after my tooth extraction. I tried to make the bleeding stop but it just kept going for hours and it finally stopped when I took some medication called DDAVP. I usually have heavy periods, just like my mom and grandma had. I don't have any other medical condition and I don't take any other medication. The doctor noticed the bruises on my legs. I had to do some lab tests. I had a normal platelet count but an abnormal ristocetin cofactor assay. I had low CB and FVIII:C levels.

Does the patient match the trial criteria? Contradiction