Clinical trial: PK Study of 90-Day Use of Vaginal Rings Containing Dapivirine and Levonorgestrel (NCT03467347)

Eligibility criteria:
Inclusion Criteria:

          1. 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 currently or have not
             been on female-to-male transition therapy 90 days prior to Enrollment.

          2. Age 18 through 45 years (inclusive) at Screening, verified per site SOPs

          3. Able and willing to provide written informed consent to be screened for and enrolled
             in MTN-044/IPM 053/CCN019

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

          5. Able to communicate in spoken and written English

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

          7. Willing to abstain from receptive intercourse (vaginal, oral, sex toy/vibrator/dildo
             and finger stimulation) and tampon use for 24 hours preceding the Enrollment Visit and
             clinical visits where samples are taken and for 1 week following each cervical biopsy
             visit

          8. Not at risk for pregnancy, defined as consistently using an effective, non-hormonal
             method of contraception per participant report at Enrollment, and intending to
             continue use of an effective, non-hormonal method for the duration of study
             participation. Effective methods include:

               1. Non-hormonal (e.g. copper) intrauterine device (IUD) inserted at least 28 days
                  prior to Enrollment

               2. Consistent and correct male condom use

               3. Sterilization (of participant or partner, as defined in site SOPs)

               4. Having sex exclusively with individuals assigned female sex at birth

               5. Sexually abstinent for 90 days prior to Enrollment, and intending to remain
                  abstinent for the duration of study participation

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

         10. HIV-uninfected based on testing performed at Screening and Enrollment

         11. Per participant report at Screening, current regular menstrual cycles of approximately
             21 to 35 days in duration with no reported intermenstrual bleeding

         12. Intact uterus with at least one ovary

         13. Per participant report at Screening and Enrollment, states a willingness to refrain
             from inserting any non-study vaginal products or objects into the vagina including,
             but not limited to spermicides, female condoms, diaphragms, other intravaginal rings,
             vaginal medications, menstrual cups, cervical caps (or any other vaginally applied
             barrier method), vaginal douches, lubricants and moisturizers, for the 24 hours
             preceding the Enrollment Visit through completion of Visit 15.

         14. 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

         15. At Screening and Enrollment, agrees not to participate in other research studies
             involving drugs, medical devices, vaginal products or vaccines after the Screening
             Visit through completion of Visit 15

        Exclusion Criteria:

          1. Body mass index greater than 40 kg/m2 at Screening

          2. 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.

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

          4. Diagnosed with an acute 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 (GC), chlamydia, trichomonas, pelvic
             inflammatory disease (PID), and/or syphilis Note: Genital warts requiring treatment
             and frequent recurrence of herpes simplex virus (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.

          5. Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study
             staff) at Screening or Enrollment, as per the 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])
             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.

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

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

               2. Chronic and/or recurrent vaginal candidiasis

               3. Has a contraindication to a progestin-only contraceptive method as defined by a
                  category 3 or 4 condition according to the CDC U.S. Medical Eligibility Criteria
                  for Contraceptive Use, 201643

               4. Use of hormonal contraception, including hormonal IUD and implants within the 28
                  days prior to Enrollment

               5. Current use or planned use of CYP3A inhibitors and inducers

               6. Current use or planned use of antibiotics and/or corticosteroids that may
                  interact with levonorgestrel

               7. Depot medroxyprogesterone acetate (DMPA) use in the 6 months prior to Enrollment
                  or any prior use without return of regular spontaneous menstrual cycles.

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

               9. Post-exposure prophylaxis (PEP) for HIV exposure within the 3 months prior to
                  Enrollment

              10. Pre-exposure prophylaxis (PrEP) for HIV prevention within the 3 months prior to
                  Enrollment

              11. Last pregnancy outcome less than 60 days prior to Enrollment

              12. Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage,
                  piercing) 45 days or less prior to Enrollment Note: Pap test at the Screening
                  Visit, colposcopy and cervical biopsies for evaluation of an abnormal Pap test as
                  well as IUD insertion/removal are not exclusionary.

              13. Currently breastfeeding or planning to breastfeed during the study period

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

          7. Has any of the following Grade 1 or higher laboratory abnormalities at Screening
             Visit:

               1. AST or ALT

               2. Creatinine

               3. Hemoglobin

          8. 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.
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