Phase 1 PK Study of the Dapivirine Vaginal Ring in Lactating Women.

PK Study of the Dapivirine Vaginal Ring in Lactating Women.

Inclusion Criteria:

Women must meet all of the following criteria (by self-report, unless otherwise indicated) to be eligible for inclusion in the study:

1. Age 18 or older at screening as verified per site SOP
2. Per participant report, at least 6 weeks postpartum at Enrollment
3. Willing and able to provide written informed consent to be screened for and take part in the study
4. Willing and able to provide adequate locator information, as defined in site SOP
5. Willing and able to communicate in spoken and written English
6. HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results Note: HIV-1/2 screening may be omitted at Enrollment if the time between Screening and Enrollment is < 30 days
7. Prior to Enrollment, breastfeeding of child has stopped
8. Participant has no intention of providing expressed breast milk to her child(ren) or to others for consumption after initiation of study product Note: Providing stored breast milk to child(ren) that has been expressed prior to study product exposure is not exclusionary
9. Willing and able to express breast milk at least twice daily for the duration of study drug exposure
10. 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-029/IPM 039 include: hormonal methods (except contraceptive VRs), intrauterine device (IUD) inserted at least 28 days prior to enrollment, engages in sex exclusively with women, sterilized (self or partner), or sexually abstinent for the past 90 days
11. 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 the Severity of Adult and Pediatric Adverse Events, Version 1.0, November 2007), or satisfactory evaluation with no treatment required of Grade 1 or higher Pap result
12. At Screening, participant states a willingness to refrain from receptive sexual activity (including penile-vaginal intercourse, anal intercourse, receptive oral intercourse, finger stimulation) and from inserting any non-study objects into the vagina (including tampons, sex toys, female condoms, diaphragms, menstrual cups, cervical caps or any other vaginal barrier method, etc.), for 24 hours prior to each clinic visit.
13. At Screening, participant states a willingness to refrain from the use of vaginal products, including, spermicides, lubricants, contraceptive VRs, douches, vaginal medications, etc., for the duration of study participation
14. Per participant report at Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, vaccines or breast milk sampling for the duration of study participation Note: Participation in observational studies is not exclusionary

Exclusion Criteria:

Women who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:

1. Participant report of any of the following:

   • History of adverse reaction to any component of dapivirine VR
   • Participation in investigational drug or device trial within 30 days prior to the Enrollment Visit (Day 0)
   • Use of vaginal medication(s) 5 days prior to Enrollment (Day 0)
   • Complication of lactation requiring treatment, e.g., mastitis

2. At the time of Screening and Enrollment, clinical evidence of milk supply less than 1 ounce per expression

3. 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

4. Grade 2 or higher AST/ALT at Screening Visit:

   Note: Otherwise eligible participants with an exclusionary AST/ALT may be retested during the screening process.

5. Positive urine pregnancy test at screening or enrollment

6. Diagnosed with urinary tract infection (UTI) at Screening or Enrollment Note: Otherwise eligible participants diagnosed with UTI during screening are offered treatment and may be enrolled after completing treatment and all symptoms have resolved.

7. Diagnosed with an STI or a reproductive tract infection (RTI) requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines at Screening or Enrollment

8. On pelvic exam, any of the following findings:

   • Incomplete postpartum involution of the uterus
   • Clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff)

9. Use of oral and/or vaginal preparations of antibiotic or antifungal medications within 5 days of Enrollment

10. At Screening or Enrollment, any social or medical condition that, in the investigator's opinion, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives