Clinical trial: Pharmacokinetic and Safety Study of a 90 Day Intravaginal Ring Containing Tenofovir (NCT03670355)

Eligibility criteria:
Inclusion Criteria:

          -  Assigned female sex at birth

               -  Note: Participants who are female at birth, who now identify as male, will not be
                  excluded so long as they are not on female-to-male transition therapy.

          -  Age 18 through 45 years (inclusive) at Screening, verified per site standard operating
             procedures (SOPs)

          -  Able and willing to provide written informed consent to be screened for and enrolled
             in MTN-038

          -  Able and willing to provide adequate locator information, as defined in site SOPs

          -  Able to communicate in spoken and written English

          -  Available for all visits and able and willing to comply with all study procedural
             requirements

          -  Willing to abstain from receptive vaginal or anal sexual activities for 72 hours prior
             to each clinical visit and for 72 hours after biopsy collection

          -  Willing to use male condoms for penile-vaginal and penile-rectal sexual intercourse
             for the duration of study participation

          -  Per participant report, using an effective method of contraception for at least 30
             days (inclusive) prior to Enrollment, and intending to continue use of an effective
             method for the duration of study participation; effective methods include:

               -  hormonal methods (except contraceptive vaginal ring)

               -  intrauterine device (IUD)

               -  sterilization (of participant or partner, as defined in site SOPs)

               -  having sex exclusively with individuals assigned female sex at birth

               -  sexually abstinent as defined by abstaining from penile-vaginal intercourse for
                  90 days prior to Enrollment, and intending to remain abstinent for the duration
                  of study participation

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

          -  HIV-uninfected based on testing performed at Screening and Enrollment (per protocol
             algorithm in the study protocol)

          -  Per participant report at Screening, regular menstrual cycles with at least 21 days
             between menses

               -  Note: This criterion is not applicable to participants who report using a
                  progestin-only method of contraception at Screening (e.g., Depo-Provera or
                  levonorgestrel-releasing IUD) nor to participants using continuous combination
                  oral contraceptive pills, as the absence of regular menstrual cycles is an
                  expected, normal consequence in this context.

          -  Per participant report at Screening and Enrollment, states a willingness to refrain
             from inserting any non-study vaginal and rectal products or objects into the vagina or
             rectum including, but not limited to spermicides, female condoms, diaphragms,
             intravaginal rings, vaginal or rectal medications, menstrual cups, cervical caps,
             douches, lubricants, and sex toys (vibrators, dildos, etc.) for the 24 hours preceding
             the Enrollment Visit and for the duration of study participation.

               -  Note: Use of tampons is permitted except for 24 hours prior to clinic visits in
                  which CVF samples are scheduled to be collected.

          -  Participants over the age of 21 (inclusive) must have documentation of a satisfactory
             Pap within the past 3 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 DAIDS 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 result

          -  At Screening and Enrollment, agrees not to participate in other research studies
             involving drugs, medical devices, vaginal or rectal products, or vaccines after the
             Screening Visit and for the duration of study participation

        Exclusion Criteria:

          -  Pregnant at Screening or Enrollment or plans to become pregnant during the study
             period

               -  Note: A documented negative pregnancy test performed by study staff is required
                  for inclusion; however, a self-reported pregnancy is adequate for exclusion from
                  the study.

          -  Diagnosed with symptomatic urinary tract infection (UTI) or reproductive tract
             infection (RTI) at Screening or Enrollment

               -  Otherwise eligible participants diagnosed with UTI/RTI during screening will be
                  offered treatment. If treatment is complete and symptoms have resolved within the
                  45 day screening window, eligible participants may be enrolled.

               -  Note: Asymptomatic BV and candidiasis are not exclusionary.

          -  Diagnosed with an acute sexually transmitted infection (STI) requiring treatment per
             current Centers for Disease Control and Prevention (CDC) guidelines
             (http://www.cdc.gov/std/treatment/) at Screening or Enrollment such as gonorrhea,
             chlamydia, trichomonas, pelvic inflammatory disease, and/or syphilis

               -  Note: Genital warts requiring treatment and frequent recurrence of HSV are
                  considered exclusionary; however, infrequent HSV outbreaks are not. Genital warts
                  requiring treatment are defined as those that cause undue burden or discomfort to
                  the participant, including bulky size, unacceptable appearance, or physical
                  discomfort. See MTN-038 Study-Specific Procedures (SSP) Manual for additional
                  information.

          -  Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study
             staff) at Screening 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 exam findings may
                  be enrolled/randomized after the findings have improved to a non-exclusionary
                  severity grading or resolved within 45 days of providing informed consent for
                  screening.

          -  Participant report and/or clinical evidence of any of the following:

               -  Known adverse reaction to any of the study products (ever), including
                  polyurethane

               -  Chronic and/or recurrent vaginal candidiasis

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

               -  Last pregnancy outcome less than 90 days prior to Enrollment

               -  Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage,
                  piercing) 45 days or less prior to Enrollment

                    -  Note: Colposcopy and cervical biopsies for evaluation of an abnormal Pap
                       test as well as IUD insertion/removal are not exclusionary.

               -  Currently breastfeeding or planning to breastfeed during the study

               -  Participation in any other research study involving drugs, medical devices,
                  vaginal or rectal products, or vaccines, in the 60 days prior to Enrollment

          -  Use of pre-exposure prophylaxis (PrEP) for HIV prevention and/or post-exposure
             prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment,
             and/or anticipated use and/or unwillingness to abstain from PrEP during trial
             participation

          -  Has any of the following laboratory abnormalities at Screening Visit:

               -  Grade 1 or higher Aspartate aminotransferase (AST) or alanine transaminase (ALT)*

               -  Grade 1 or higher Hemoglobin*

               -  Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault
                  formula

               -  Positive Hepatitis B surface antigen result

                    -  Note: Otherwise eligible participants with an exclusionary laboratory result
                       may be re-tested during the screening process. If a participant is re-tested
                       and a non-exclusionary result is documented within 45 days of providing
                       informed consent for screening, the participant may be enrolled.

          -  Has any other condition that, in the opinion of the IoR/designee, would preclude
             informed consent, make study participation unsafe, complicate the interpretation of
             study outcome data, or otherwise interfere with achieving the study objectives
             including any significant uncontrolled active or chronic medical condition.

        (*) Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse
        Events Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for
        Use in Microbicide Studies [Dated November 2007])
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 45 Years

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