Clinical trial: Safety and Pharmacokinetics of Intravaginal Rings Containing Vicriviroc (MK-4176) and/or MK-2048 (NCT02356302)

Eligibility criteria:
Inclusion Criteria:

          -  Born female. Note: Participants who were 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 SOPs

          -  Able and willing to provide written informed consent to be screened for and take part
             in this study (MTN-027)

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

          -  HIV-uninfected, based on testing performed by study staff at Screening and Enrollment
             (per applicable algorithm in Appendix II of the protocol) and willing to receive
             results

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

          -  At Screening, participant states willingness to abstain from receptive sexual activity
             (including penile-vaginal intercourse, anal intercourse, receptive oral intercourse,
             finger stimulation, and the use of sex toys) for the 5 days prior to the Enrollment
             Visit and for the duration of study participation

          -  Per participant report, using an effective method of contraception at Enrollment, and
             intending to continue the use of an effective method for the duration of study
             participation. Effective methods for MTN-027 include: hormonal methods (except
             contraceptive IVRs), intrauterine device (IUD) inserted at least 28 days prior to
             enrollment, engages in sex exclusively with women, sterilized (self or partner),
             and/or sexually abstinent for the past 90 days.

          -  Women 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 to the DAIDS
             Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004
             (Clarification dated August 2009), or satisfactory evaluation with no treatment
             required of Grade 1 or higher Pap result

          -  Per participant report at Screening and Enrollment, agrees not to participate in other
             research studies involving drugs, medical devices, or vaginal products for the
             duration of study participation

          -  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.

          -  At Screening, participant 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, contraceptive IVRs, vaginal medications,
             menstrual cups, cervical caps (or any other vaginal barrier method), douches,
             lubricants, sex toys (vibrators, dildos, etc.) for the 5 days prior to Enrollment and
             for the duration of their study participation

        Exclusion Criteria:

          -  Participant report of any of the following at Screening and/or Enrollment:

               -  History of adverse reactions to any of the components of the study products

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

               -  Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to
                  Enrollment

               -  Pre-exposure prophylaxis (PrEP) for HIV prevention within the 6 months prior to
                  Enrollment

               -  Regular use and/or anticipated regular use during the period of study
                  participation of CYP3A inducer(s) and/or inhibitor(s)

               -  Use and/or anticipated use during the period of study participation of
                  female-to-male transition therapy

               -  Chronic and/or recurrent candidiasis

               -  Gonorrhea, chlamydia, and/or syphilis diagnosis in the 6 months prior to
                  Enrollment

               -  Last pregnancy outcome 90 days or less prior to Screening

               -  Currently breastfeeding

               -  Has had a hysterectomy

               -  Intends to become pregnant within the next 3 months

               -  Has plans to relocate away from the study site area in the next 3 months

               -  Current sexual partner is known to be HIV-positive

          -  Reports participating in any other research study involving drugs, medical devices, or
             vaginal products within 60 days or less prior to enrollment

          -  At Screening or Enrollment, as determined by the IoR/designee, any significant
             uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic,
             gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or
             infectious disease

          -  Has any of the following laboratory abnormalities at Screening:

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

               -  Calculated creatinine clearance less than 60 mL/min by the Cockcroft-Gault
                  formula, where creatinine clearance (female) in mL/min = (140 - age in years) x
                  (weight in kg) x (0.85)/72 x (creatinine in mg/dL)

               -  Hemoglobin Grade 1 or higher

               -  Platelet count Grade 1 or higher

               -  White blood count Grade 2 or higher

               -  Positive HBsAg test result

               -  Positive anti-hepatitis C virus (HCV) test result

               -  International normalized ratio (INR) greater than 1.5 × the site laboratory upper
                  limit of normal (ULN)

               -  Note: Otherwise eligible participants with an exclusionary test result (other
                  than HIV, hepatitis B virus [HBV], or HCV) can 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.

          -  Pregnant at either Screening or Enrollment. Note: A documented negative pregnancy test
             performed by study staff is required for inclusion; however a self-reported pregnancy
             is adequate for exclusion from screening/enrollment into the study.

          -  Diagnosed with urinary tract infection (UTI) at Screening or Enrollment. Note:
             Otherwise eligible participants diagnosed with UTI during screening will be offered
             treatment. If within the 45 day screening window treatment is complete and symptoms
             have resolved the participant may be enrolled.

          -  Diagnosed with pelvic inflammatory disease, reproductive tract infection (RTI) or a
             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. Note: With the exception of gonorrhea, chlamydia, and/or
             syphilis, otherwise eligible participants diagnosed with a RTI during screening will
             be offered treatment. If within the 45 day screening window treatment is complete and
             symptoms have resolved the participant may be enrolled.

          -  At Enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding
             (observed by study clinician or designee) 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. Note: Cervical friability 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.

          -  At Screening, severe pelvic relaxation such that either the vaginal walls or the
             uterine cervix descend beyond the vaginal introitus with valsalva maneuver or has
             pelvic anatomy that compromises the ability to adequately assess vaginal safety

          -  Has 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 study objectives
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? 1