Pharmacokinetics of Two Intravaginal Rings (IVRs) Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048

NCT02419456 | Completed Phase 1 DMC

• 2 other identifiers: MTN-02812022
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Intravaginal rings (IVRs) may offer an ideal way to deliver antiretroviral (ARV) drugs to prevent HIV infection. This study will evaluate the pharmacokinetics and safety of two IVRs containing different doses of a combination of two HIV ARV drugs, vicriviroc (VCV) (MK-4176) and MK-2048, in healthy, HIV-uninfected women.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (5)

• Assessment of vaginal fluid concentrations of MK-4176 and MK-2048 during and after IVR use

  Measured through Day 35

• Assessment of blood plasma concentrations of MK-4176 and MK-2048 during and after IVR use

  Measured through Day 35

• Assessment of cervical tissue concentrations of MK-4176 and MK-2048 during and after IVR use

  Measured through Day 35

• Number of genitourinary events Grade 1 or higher judged to be related to study product

  As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009), Addendum 1, (Female Genital Grading Table for Use in Microbicide Studies)

  Measured through Day 35

• Number of adverse events Grade 2 or higher

  As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009)

  Measured through Day 35

Secondary Outcomes (1)

• Measurement of residual drug levels in IVRs

  Measured through Day 35

Study Arms (2)

MK-2048A Intravaginal Ring (IVR) (Low Dose)

EXPERIMENTAL

The MK-2048A IVR (Low Dose) will be inserted during the enrollment visit (Day 0), and it will be removed on Day 28.

Drug: MK-2048A IVR (Low Dose)

MK-2048A IVR (Original Dose)

EXPERIMENTAL

The MK-2048A IVR (Original Dose) will be inserted during the enrollment visit (Day 0), and it will be removed on Day 28.

Drug: MK-2048A IVR (Original Dose)

Interventions

MK-2048A IVR (Low Dose) DRUG

Contains 91 mg of vicriviroc (MK-4176) and 10 mg of MK-2048.

MK-2048A Intravaginal Ring (IVR) (Low Dose)

MK-2048A IVR (Original Dose) DRUG

Contains 182 mg of vicriviroc (MK-4176) and 30 mg of MK-2048.

MK-2048A IVR (Original Dose)

Eligibility Criteria

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

You may qualify if:

• 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 (standard operating procedures)
• Able and willing to provide written informed consent to be screened for and take part in this study (MTN-028)
• 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-028 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. If otherwise eligible women do not have documentation of a recent Pap test, one may be performed at the screening visit.
• 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

You may not qualify if:

• Participant report of any of the following at screening 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 at screening or enrollment

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Liu AY, Zhang J, Anderson PL, Wagner T, Pan Z, Peda M, Gomez K, Beamer M, Jacobson C, Strizki J, Dezzutti CS, Piper JM; MTN-028 Protocol Team for the Microbicide Trials Network. Phase 1 Pharmacokinetic Trial of 2 Intravaginal Rings Containing Different Dose Strengths of Vicriviroc (MK-4176) and MK-2048. Clin Infect Dis. 2019 Mar 19;68(7):1129-1135. doi: 10.1093/cid/ciy652.

  PMID: 30289444 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Albert Liu, MD, MPH

  San Francisco Department of Public Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 17, 2015
• Study Start: June 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: November 11, 2021

Record last verified: 2016-05

Locations

US (1)