Clinical trial: Tenofovir Levels Following Local Application of Tenofovir Reduced-Glycerin 1% Gel (NCT01768962)

Eligibility criteria:
Inclusion Criteria:

          1. Age 21 through 45 years (inclusive) at Screening

          2. Able and willing to provide written informed consent

          3. Able and willing to comply with all study procedure requirements, including, clinical
             and laboratory assessments, vaginal and rectal examinations, urine and blood testing,
             as well as attendance at all scheduled study visits

          4. In general good health at Screening and Enrollment as determined by the Investigator
             of Record (IoR)/ or designee

          5. Negative pregnancy test at Screening and Enrollment

          6. HIV-negative at Screening and Enrollment

          7. Able and willing to provide adequate locator information

          8. Willingness to use study-provided male condoms for the duration of study participation
             for penetrative intercourse

          9. Per participant report at Screening, regular menstrual cycles with at least 21 days
             between menses (does not apply to participants who report using a progestin-only
             method of contraception at screening, e.g., Depo-Provera, progesterone-containing IUDs
             or extended use of oral contraceptives)

         10. Per participant report at Enrollment, using an effective method of contraception and
             intending to use an effective method for the duration of study participation;
             effective methods include:

               -  Hormonal methods, excluding vaginal rings

               -  Intrauterine device (IUD) inserted at least 42 days prior to Enrollment (but not
                  past the maximum length of recommended usage according to package instructions)

               -  Sterilization of participant or partner at least 42 days prior to Enrollment

               -  Self-identifies as a woman who has sex with women exclusively

               -  Sexually abstinent for the at least 90 days prior to enrollment and the intention
                  to remain sexually abstinent for the duration of study participation

         11. Per participant report at Screening, states a willingness to refrain from inserting
             any non-study vaginal or rectal products or objects into the vagina or rectum,
             including but not limited to, spermicides, female condoms, diaphragms, contraceptive
             vaginal rings, vaginal medications, menstrual cups, cervical caps (or any other
             vaginal barrier method), vaginal/rectal douches, enemas, non-study approved
             lubricants, sex toys (vibrators, dildos, etc.), and tampons for the duration of the
             study product use periods and for 24 hours prior to each scheduled study clinic visit.

         12. Pap result consistent with Grade 0 according to the Female Genital Grading Table for
             Use in Microbicide Studies Addendum 1 to the Division of AIDS (DAIDS) Table for
             Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004
             (Clarification dated August 2009) or satisfactory evaluation of non-Grade 0 Pap result
             with no treatment required per clinical judgment of IoR or designee in the 12 calendar
             months prior to the Enrollment Visit

         13. At Screening, participant agrees not to take part in other research studies involving
             drugs, medical devices, or vaginal/rectal products for the duration of study
             participation (including the time between the Screening and Enrollment visits)

             Participants in the biopsy subset must also meet the following criteria at Screening
             to be eligible for inclusion:

         14. Willing to abstain from inserting anything into the vagina or rectum for 72 hours
             prior to and following the collection of these samples, including vaginal and rectal
             intercourse

         15. Willing to restrict the use of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin
             and/or other drugs that are associated with the increased likelihood of bleeding
             following mucosal biopsy collection for 72 hours prior to and following the collection
             biopsies

        Exclusion Criteria:

          1. Participant report of any of the following:

               1. Known adverse reaction to the study product (ever)

               2. Known adverse reaction to latex (ever)

               3. Current male sex partner with known history of adverse reaction to latex (ever)

               4. History of serum HBsAg positivity (ever)

               5. Non-therapeutic injection drug use in the 12 calendar months prior to Enrollment

               6. STI or reproductive tract infection (RTI) requiring treatment in the 6 calendar
                  months prior to Enrollment

               7. Post-exposure prophylaxis (PEP) for possible HIV-1 infection within the 6
                  calendar months prior to Enrollment

               8. Last pregnancy outcome within 90 days or less prior to Enrollment

               9. Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage)
                  within the 42 days prior to Enrollment Note: This does not include biopsy for the
                  evaluation of an abnormal pap result or endometrial biopsy that occurred more
                  than 7 days prior to Enrollment, provided that all other inclusion/exclusion
                  criteria are met.

              10. Participation in any other research study involving drugs, medical devices or
                  vaginal products 42 days or less prior to Enrollment

              11. Anticipated IUD replacement within the next 3 months or an IUD inserted 42 days
                  or less prior to Enrollment

              12. Participant report at Screening and/or Enrollment intention of becoming pregnant
                  in the next 3 months

              13. Currently breastfeeding at the time of Screening and/or Enrollment

              14. History of bleeding problems (Participants in the biopsy subset only)

          2. Laboratory abnormalities at Screening greater than or equal to a Grade 2*:

               1. Aspartate aminotransferase (AST) or alanine transaminase (ALT)

               2. Hemoglobin

               3. Platelet count

               4. Serum creatinine Otherwise eligible participants with an exclusionary test
                  result(s) listed above may be re-tested during the screening process. If a
                  participant is re-tested and a non-exclusionary result is documented within the
                  42 days of providing informed consent, the participant may be enrolled.

          3. Urinary tract infection (UTI) at Screening and/or Enrollment Note: Otherwise eligible
             participants diagnosed with UTI during Screening will be offered treatment and may be
             enrolled after completing treatment and all symptoms have resolved. If treatment is
             completed and symptoms have resolved within 42 days of obtaining informed consent, the
             participant may be enrolled.

          4. Pelvic inflammatory disease or an STI or RTI requiring treatment per current WHO
             guidelines at Screening and/or Enrollment

          5. Clinically apparent Grade 2 or higher pelvic** and/or rectal*** examination finding
             (observed by study staff) at Screening and/or Enrollment Note: Cervical bleeding
             associated with speculum insertion and/or specimen collection judged to be within the
             range of normal according to the clinical judgment of the IoR/designee is considered
             expected non-menstrual bleeding and is not exclusionary.

             Note: Otherwise eligible participants with exclusionary pelvic and/or rectal
             examination findings may be enrolled/randomized after the findings have improved to a
             non-exclusionary severity grading or resolved. If improvement to a non-exclusionary
             grade or resolution is documented within 42 days of providing informed consent, the
             participant may be enrolled.

          6. Any other condition that, in the opinion of the IoR/designee, would preclude informed
             consent, make study participation unsafe, complicate interpretation of study outcome
             data, or otherwise interfere with achieving the study objectives

               -  per the Division of AIDS Table for Grading the Severity of Adult and Pediatric
                  Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009) **
                  per the Division of AIDS Table for Grading the Severity of Adult and Pediatric
                  Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009),
                  Addendum 1 Female Genital Grading Table for Use in Microbicide Studies *** per
                  the Division of AIDS Table for Grading the Severity of Adult and Pediatric
                  Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009),
                  Addendum 3 Rectal Grading Table for Use in Microbicide Studies (Clarification
                  dated May 2012).
Female
Accepts Healthy Volunteers
Subject must be at least 21 Years old.
Subject must be at most 45 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction