PK Study of 90-Day Use of Vaginal Rings Containing Dapivirine and Levonorgestrel

NCT03467347 | Completed Phase 1 FDA Drug

• 2 other identifiers: MTN-044/IPM 053/CCN0195UM1AI068633
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I single-center, two-arm, open-label, randomized study in healthy HIV-negative women to evaluate the pharmacokinetics, safety, and bleeding patterns associated with 90-day use of matrix vaginal rings containing 200 mg Dapivirine and 320 mg Levonorgestrel.

Conditions

Healthy; Contraception; Contraceptive Usage; Women

Keywords

Healthy Women; Contraception; Vaginal Ring; dapivirine; Levonorgestrel

Outcome Measures

Primary Outcomes (3)

• Evaluate pharmacokinetics by assessing changes in baseline of DPV and LNG concentrations in plasma.

  90 days

• Evaluate pharmacokinetics by assessing changes in baseline of DPV and LNG concentrations in cervicovaginal fluid.

  90 days

• Evaluate pharmacokinetics by assessing changes in baseline of DPV concentration in cervical tissue.

  90 days

Secondary Outcomes (2)

• Incidence of Grade 2 or higher genitourinary adverse events as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected V 2.1,or Addendum 1 Female Genital Grading Table for Use in Microbicide Studies

  90 days

• Incidence of Grade 3 or higher adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

  90 days

Study Arms (2)

VR used continuously for approximately 90 days

EXPERIMENTAL

One silicone elastomer vaginal ring (VR) containing the active 200 mg dapivirine (DPV) and 320 mg levonorgestrel (LNG), used continuously for approximately 90 days.

Drug: VR: 200 mg DPV + 320 mg LNG

VR used cyclically for approximately 90 days

EXPERIMENTAL

One silicone elastomer vaginal ring (VR) containing the active 200 mg dapivirine (DPV) and 320 mg levonorgestrel (LNG), used cyclically for approximately 90 days. Use the VR for 28 days, remove for 2 days.

Drug: VR: 200 mg DPV + 320 mg LNG

Interventions

VR: 200 mg DPV + 320 mg LNG DRUG

One silicone elastomer vaginal ring (VR) containing the active ingredients dapivirine (DPV) and levonorgestrel (LNG), formulated as IPM VR: 200 mg DPV + 320 mg LNG (Ring-102)

VR used continuously for approximately 90 days; VR used cyclically for approximately 90 days

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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 enrolled in MTN-044/IPM 053/CCN019
• 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 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
• 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:
• Non-hormonal (e.g. copper) intrauterine device (IUD) inserted at least 28 days prior to Enrollment
• Consistent and correct male condom use
• Sterilization (of participant or partner, as defined in site SOPs)
• Having sex exclusively with individuals assigned female sex at birth
• Sexually abstinent 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

You may not qualify if:

• Body mass index greater than 40 kg/m2 at Screening
• Diagnosed with symptomatic urinary tract infection (UTI) or reproductive tract infection (RTI) at Screening or Enrollment
• Participant report and/or clinical evidence of any of the following:
• Known adverse reaction to any component of the study product (ever)
• Chronic and/or recurrent vaginal candidiasis
• 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
• Use of hormonal contraception, including hormonal IUD and implants within the 28 days prior to Enrollment
• Current use or planned use of CYP3A inhibitors and inducers
• Current use or planned use of antibiotics and/or corticosteroids that may interact with levonorgestrel
• Depot medroxyprogesterone acetate (DMPA) use in the 6 months prior to Enrollment or any prior use without return of regular spontaneous menstrual cycles.
• Non-therapeutic injection drug use in the 12 months prior to Enrollment
• Post-exposure prophylaxis (PEP) for HIV exposure within the 3 months prior to Enrollment
• Pre-exposure prophylaxis (PrEP) for HIV prevention within the 3 months prior to Enrollment
• Last pregnancy outcome less than 60 days prior to Enrollment
• Currently breastfeeding or planning to breastfeed during the study period

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Division of AIDS, US National Institute of Allergy and Infectious Diseases: collaborator
• National Institute of Mental Health (NIMH): collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Magee-Women'S Res Inst and Foundation

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Friedland BA, Gundacker H, Achilles SL, Chen BA, Hoesley C, Richardson BA, Kelly CW, Piper J, Johnson S, Devlin B, Steytler J, Kleinbeck K, Dangi B, Friend C, Song M, Mensch B, van der Straten A, Jacobson C, Hendrix CW, Brown J, Blithe D, Hiller SL; MTN-030/IPM 041 and MTN-044/IPM 053/CCN019 Protocol Teams for the Microbicide Trials Network and the Contraceptive Clinical Trials Network. Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development. PLoS One. 2025 Jan 14;20(1):e0312957. doi: 10.1371/journal.pone.0312957. eCollection 2025.

  PMID: 39808648 DERIVED

MeSH Terms

Conditions

Contraception Behavior

Condition Hierarchy (Ancestors)

Reproductive Behavior; Behavior

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 16, 2018
• Study Start: July 17, 2018
• Primary Completion: August 30, 2019
• Study Completion: October 7, 2019
• Last Updated: October 9, 2019

Record last verified: 2019-10

Locations

US (1)