Clinical trial: PK/PD of Single Dose Dapivirine Vaginal Film (NCT01924091)

Eligibility criteria:
Inclusion Criteria:

          1. 18 years of age or older with a history of receptive vaginal intercourse.

          2. HIV negative by EIA within 28 days of enrollment.

          3. Understand and agree to local STI reporting requirements.

          4. Able and willing to provide written informed consent to take part in the study.

          5. Able and willing to provide adequate information for locator purposes.

          6. Availability to return for all study visits, barring unforeseen circumstances.

          7. Availability to return for the second formulation dosing at the same time in the
             subject's menstrual cycle as when the first formulation was administered, at least 10
             days before menses.

          8. Willing to abstain from vaginal intercourse and insertion of anything (e.g., drug,
             vaginal douche, or sex toy) in vagina for 72 hours before each study product exposure,
             and 7 days following each vaginal sampling procedure.

          9. Willingness to have partner(s) use condoms (must not contain Nonoxynol-9) for the
             duration of the study.

         10. Agree not to participate in other research studies involving drugs and/or medical
             devices.

         11. Negative qualitative urine pregnancy test.

         12. Per participant report, using an effective method of contraception at enrollment;
             hormonal method (except vaginal ring) used continuously for the past 30 days;
             intrauterine device (IUD [copper or hormonal] inserted at least 30 days prior to
             enrollment); female sterilization; abstinent from sexual activity with male partner
             for the past 30 days; or sexual activity with vasectomized partner; and willingness to
             use effective method of contraception until the completion of final scheduled study
             visit if enrolled.

         13. Willingness to remain in the research unit for up to 24 hours on each of two dosing
             days, -

        Exclusion Criteria:

          1. Current sexual partner known by participant to be HIV seropositive.

          2. Individuals who, by history, engage in condom-less intercourse with HIV-infected
             partners, or partners that have unknown HIV serostatus, or women who exchange sex for
             money, shelter, or gifts.

          3. Active sexually transmitted infection or documented treatment of sexually transmitted
             infections including, but not limited to: chlamydia, gonorrhea, syphilis, trichomonas,
             cervicitis or PID within 6 months prior to enrollment.

          4. Known history of genital HSV (diagnosed by either clinical or laboratory test).

          5. Symptomatic vaginal candidiasis or bacterial vaginosis.

          6. Undiagnosed irregular uterine bleeding

          7. Pathology of the female genital tract, which in the judgment of the investigator might
             increase the risk of the study to the research participant.

          8. Individuals who are status post hysterectomy.

          9. History of any cervicovaginal procedure (i.e. colposcopy with cervical biopsy) within
             the past 2 months. Individuals who have a history of cone biopsy or extensive loop
             electrosurgical excision procedure (LEEP), which in the judgment of the investigator
             may affect permeability assessment.

         10. Any known primary or secondary uro-genital malformations, which in the assessment of
             the investigator may interfere with the intended urine collection for PK studies.

         11. Use of vaginally administered medications within 4 week of enrollment

         12. Any active urinary tract infection

         13. By history, subjects with irregular menstrual cycles.

         14. At screening:

               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than
                  1.5 X the site laboratory ULN (upper limit of normal)

               -  Hemoglobin less than 10.0 g/dL

               -  Platelet count less than 100,000/mm3

               -  Other safety tests outside of the normal range that in the judgment of the
                  investigator may interfere with conduct of the study.

               -  Positive findings on urinalysis that are clinically significant in the opinion of
                  the investigator

         15. Estimated creatinine clearance < 60 ml/min based on established nomograms

         16. Recent history (past 6 months) of injection drug use or, a level of alcohol use that,
             in the judgement of the Investigator of Record, may interfere with the conduct of this
             study.

         17. Unwillingness to refrain from aspirin and NSAIDs product use for one week prior to and
             one week post study procedures.

         18. Use of warfarin or heparin.

         19. Use of systemic immunomodulatory medications within 4 weeks of enrollment.

         20. Use of product containing nonoxynol-9 within 4 weeks of enrollment.

         21. Use of any investigational products within 4 weeks of enrollment.

         22. Any other medical conditions deemed not safe for participation by the investigator.

         23. Any individual that is actively breast feeding.

         24. Post-menopausal defined as 12 months of amenorrhea.

             -
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.


Patient description (medical language): A 43-year-old woman, gravida 3 para 3, comes to the clinic complaining of recently painful menstrual cycles.  The patient's last menstrual period was 2 weeks ago. Urine β-hCG is negative. Menarche was at age 12, and menstrual periods occur every 28 days and lasts for 5 days.  She is sexually active with her husband and does not have pain with intercourse. BMI is 23 kg/m2 and Vital signs are normal.  On physical examination, the uterus is uniformly enlarged and tender. She is candidate for hysterectomy with the diagnosis of adenomyosis.

Patient description (patient's own words): I'm 43, and I paid a visit to my doctor because my last few periods were insanely painful. My last periods were 2 weeks ago. I already had three pregnancies that gave me the three lovely children. I did a urine test to check for potential pregnancy, and it came back negative. I started to have my periods at the age of 12, and I have been pretty regular with periods every 28 days for 5 days. I'm sexually active with my husband and I do not have any pain when we have sex. My BMI is 23 and my vitals were normal. The doctor performed a physical exam and found that my uterus was tender and enlarged. She proposed me a hysterectomy and diagnosed me with adenomyosis.

Does the patient match the trial criteria? Entailment