Clinical trial: PrEP-Pod-IVR (TDF-FTC/Placebo IVR 28 Day Crossover Study) (NCT03255915)

Eligibility criteria:
Inclusion Criteria:

          1. Age of 18 through 45 years at screening, verified per site SOP

          2. Female participants, born female

          3. Not pregnant or breastfeeding

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

          5. Willing and able to

               -  communicate in English

               -  provide written informed consent to take part in the study

               -  provide adequate locator information, as defined in site SOP

               -  complete all required study procedures, including phone surveys, daily vaginal
                  swabs, and reliably store swabs in freezer

          6. Must agree

               -  not to participate in other concurrent interventional and/or drug trials

               -  to use study-provided condoms for vaginal or anal intercourse for the duration of
                  the study

               -  to abstain from use of any vaginal products (e.g., lubricants, feminine hygiene
                  products, vaginally administered contraceptive products, sex toys) other than
                  study products for the duration of the study beginning at enrollment Note:
                  Tampons may be used during menses, but must be discontinued 72 hours prior to
                  study visits and for 7 days after biopsy procedures. Menstrual pads will be
                  provided to participants.

               -  to abstain from receptive oral, vaginal, or anal intercourse during the first
                  week after each pod-IVR insertion and for 2 days before and 7 days after biopsy
                  procedures

               -  to abstain from insertion of anything in the vagina (e.g., tampon, finger, sex
                  toy, lubricants, medication, douche) during the first week after each pod-IVR
                  insertion and for 2 days before and 7 days after biopsy procedures

          7. Understands and agrees to local STI reporting requirements

          8. HIV-1 seronegative at screening

          9. Must be in general good health in the opinion of the investigator

         10. Regular menstrual cycles of approximately 21 to 35 days apart with no untreated
             intermenstrual menstrual bleeding Note: This criterion is not applicable to
             participants using continuous combination oral contraceptive pills or progestin-only
             methods (such as Depo-Provera or levonorgestrel-releasing IUD), as the absence of
             regular menstrual cycles is an expected, normal consequence in this context.

         11. Satisfactory cervical Pap result in the 36 calendar months prior to Enrollment
             consistent with Grade 0 according to the Female Genital Grading Table for Use in
             Microbicide Studies [Addendum 1, Dated November 2007], or if Grade 1 or higher Pap
             result has had a satisfactory evaluation with no treatment required per American
             Society for Colposcopy and Cervical Pathology (ASCCP) guidelines in the 12 calendar
             months prior to Enrollment

         12. Using an effective method of contraception and intending to continue use of an
             effective method for the duration of study participation. Acceptable methods include:

               -  hormonal methods (except contraceptive vaginal rings)

               -  IUD

               -  sterilization of participant or partner

             In addition to the criteria listed above, participants who agree to have rectal
             biopsies collected must meet the following criteria:

         13. Must agree to abstain from insertion of anything in the rectum (e.g., finger, sex toy,
             lubricants, medication, enema) during the first week after each pod-IVR insertion and
             for 2 days before and 7 days after biopsy procedures

        Male sexual partner(s) who meet the following criteria are eligible for inclusion in the
        study:

          1. Age of 18 years or over

          2. Has a female sexual partner enrolled in the study

          3. Willing and able to

               -  communicate in English

               -  provide written informed consent to take part in the study

               -  provide adequate locator information, as defined in site SOP

               -  complete in-depth interview via video conference

        Exclusion Criteria:

        Individuals who meet any of the following criteria will be excluded from the study:

          1. Undergoing or completed gender reassignment

          2. Participant reports any of the following at Screening:

               1. Has plans to relocate away from the study site area during the period of study
                  participation

               2. Pregnant, less than 3 months post-partum, or lactating

               3. Intends to become pregnant during the period of study participation

               4. Current or planned use of an IVR

               5. Known HIV-infected partners

               6. Non-therapeutic injection drug use in the 6 months prior to screening

               7. History of autoimmune disease

               8. History of toxic shock syndrome

               9. History of adverse reaction to TDF, FTC, silicone, or microcrystalline cellulose

              10. PrEP or Post-exposure prophylaxis for HIV exposure within 6 months prior to
                  screening

              11. Use of systemic immunomodulatory medications within the 4 weeks prior to the
                  Enrollment

              12. Use of vaginally or rectally administered medications or products (including
                  condoms) containing Nonoxynol-9 (N-9) within the 4 weeks prior to the Enrollment

              13. Participating in another research study involving drugs or medical devices within
                  the 4 weeks or 5 half-lives (if known) prior to the Enrollment

              14. Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage,
                  piercing) within 60 days prior to Enrollment

             Note: Colposcopy and cervical biopsies for evaluation of an abnormal Pap smear as well
             as IUD removal are not exclusionary

          3. Per participant report at screening, anticipated use and/or unwillingness to abstain
             from the following medications during the period of study participation:

               1. Heparin, including Lovenox® (enoxaparin sodium)

               2. Warfarin

               3. Plavix® (clopidogrel bisulfate)

               4. Any other drugs that are associated with increased likelihood of bleeding
                  following mucosal biopsy (e.g., daily high dose aspirin, Pradaxa®)

               5. NSAID use for 5 half-lives prior to biopsy (e.g. ibuprofen for 1 day, naproxen
                  for 4 days).

               6. Rectally or vaginally administered medications (including over-the-counter
                  products)

          4. History of significant gastrointestinal bleeding in the opinion of the investigator

          5. Abnormalities of the cervical, vaginal, or colorectal mucosa, or significant
             symptom(s), which in the opinion of the clinician represents a contraindication to
             protocol-required biopsies (including but not limited to presence of any unresolved
             injury, infectious or inflammatory condition of the local mucosa, and presence of
             symptomatic external hemorrhoids). Erythema is not exclusionary.

             • Includes any clinically apparent Grade 2 or higher pelvic examination finding
             (observed by study staff) at Screening or Enrollment, as per the Female Genital
             Grading Table for Use in Microbicide Studies [Addendum 1, Dated November 2007]

          6. At screening: participant-reported symptoms and/or clinical or laboratory diagnosis of
             active rectal or reproductive tract infection requiring treatment per current CDC
             guidelines or symptomatic urinary tract infection (UTI). Infections requiring
             treatment include symptomatic bacterial vaginosis, symptomatic vaginal candidiasis,
             trichomoniasis, chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions,
             chancroid, pelvic inflammatory disease, genital sores or ulcers, cervicitis, or
             symptomatic genital warts requiring treatment (i.e., those that cause undue burden or
             discomfort to the participant).

             Note:

               -  An HSV-1 or HSV-2 seropositive diagnosis with no active lesions is allowed, since
                  treatment is not required

               -  One re-screening after documented treatment will be allowed

          7. Has any of the following laboratory abnormalities at Screening:

             Note: Grade is per Version 2.1 of the DAIDS Toxicity Table

               1. Hemoglobin Grade 1 or higher

               2. Platelet count Grade 1 or higher

               3. International Normalized Ratio (INR) Grade 2 or higher

               4. White blood cell count Grade 2 or higher

               5. Calculated creatinine clearance ≤ 80 mL/minute using the Cockcroft-Gault equation

               6. Grade 2 or higher ALT and/or AST (i.e., ≥ 2.5x the site laboratory upper limit of
                  normal [ULN])

               7. Positive for Hepatitis B surface antigen (HBsAg)

               8. Positive for Hepatitis C antibody (HCV Ab)

          8. Has any other condition that, in the opinion of the Principal Investigator or
             designee, would preclude informed consent, make study participation unsafe, complicate
             interpretation of study outcome data, or otherwise interfere with achieving study
             objectives

        Male sexual partner(s) who meet the following criteria are not eligible for inclusion in
        the study:

        1) Female partner did not utilize study product
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