Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048

NCT04319718 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: STUDY191001201U19AI120249
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof of concept study to determine whether an extended release vaginal film can deliver drug for seven days. Two film formulations containing MK-2048 which differ by dissolution and spreadability attributes will be compared for safety and pharmacokinetic outcomes.

Conditions

Pharmacokinetics; Safety

Keywords

Vagina; Film; Extended Release

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Grade 2 or Higher Adverse Events

  Number of participants who experience Grade 2 or higher adverse events

  Through study completion, approximately 28 days

Secondary Outcomes (5)

• Area Under the Plasma Concentration Versus Time Curve of MK-2048

  Through study completion, approximately 28 days

• Area Under the Cervical Tissue Homogenate Concentration Versus Time Curve of MK-2048

  Through study completion, approximately 28 days

• Area Under the Cervicovaginal Lavage Fluid Concentration Versus Time Curve of MK-2048

  Through study completion, approximately 28 days

• Area Under the Rectal Swab Eluent Concentration Versus Time Curve of MK-2048

  Through study completion, approximately 28 days

• Area Under the Vaginal Swab Eluent Concentration Versus Time Curve of MK-2048

  Through study completion, approximately 28 days

Other Outcomes (3)

• Median Fold Change in Percent Inhibition of Human Immunodeficiency Virus-1 Replication in Cervicovaginal Lavage Fluid

  Through study completion, approximately 28 days

• Human Immunodeficiency Virus-1 p24 Core Protein Titer in Cervical Biopsies

  Through study completion, approximately 28 days

• Mean Change in Nugent Score

  Through study completion, approximately 28 days

Study Arms (2)

High Eudragit MK-2048 vaginal film

ACTIVE COMPARATOR

Single use of 2" x 2" vaginal film containing 30 mg of MK-2048 and 68.1 mg of ammonio methacrylate copolymer type B (Eudragit®).

Combination Product: MK-2048 High Eudragit Vaginal Film

Low Eudragit MK-2048 vaginal film

ACTIVE COMPARATOR

Single use of 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®).

Combination Product: MK-2048 Low Eudragit Vaginal Film

Interventions

MK-2048 High Eudragit Vaginal Film COMBINATION_PRODUCT

2" x 2" vaginal film containing 30 mg of MK-2048 and either 68.1 mg of ammonio methacrylate copolymer type B (Eudragit®)

High Eudragit MK-2048 vaginal film

MK-2048 Low Eudragit Vaginal Film COMBINATION_PRODUCT

2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)

Low Eudragit MK-2048 vaginal film

Eligibility Criteria

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

You may qualify if:

• Able and willing to provide written informed consent.
• Willing to use an effective method of birth control throughout the duration of the study. Examples of effective methods include: hormonal methods (other than NuvaRing®), intrauterine device, bilateral tubal ligation, same sex partner, partner with a vasectomy, abstinence (defined as no vaginal sex for one month prior to screening).
• Able and willing to provide adequate locator information
• HIV-uninfected based on testing performed by study staff at screening
• In general good health as determined by the site clinician
• Agree to be sexually abstinent, including use of sex toys, from visit 2 (Enrollment) until visit 7 (7 days after the biopsy visit) and 48 hours prior to all study visits.
• Agree to refrain from use of vaginal device or products (for example, lubricants, creams, suppositories) throughout participation in the study. Tampons may be used except between visit 5 (biopsy visit) and visit 7 (day 14).
• Willingness to undergo all study-related assessments and follow all study-related procedures
• At screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products while enrolled in this trial
• Participants over the age of 21 (inclusive) must have documentation of a satisfactory Pap within three years prior to Enrollment consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the Division of Acquired Immune Deficiency Syndrome Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or satisfactory evaluation with no treatment required of grade 1 or higher Pap results. If no documentation of a Pap smear can be provided, a Pap smear will be collected at the screening visit.

You may not qualify if:

• Menopause (as defined as amenorrhea for one year or more without an alternative etiology)
• Hysterectomy
• Participant report of any of the following:
• Known adverse reaction to any of the study products (ever)
• Non- therapeutic injection drug use in the 12 months prior to Screening
• Surgical procedure involving the pelvis in the 60 days prior to enrollment (includes dilation and curettage or evacuation, and cryosurgery; does not include cervical biopsy for evaluation of an abnormal pap smear)
• Participation in a drug, spermicide and/or microbicide study in the 30 days prior to enrollment
• Currently pregnant or pregnancy within 42 days prior to enrollment
• Currently lactating
• Use of a diaphragm, NuvaRing®, or spermicide for contraception
• Urogenital infection or suspected infection within 7 days of enrollment including: symptomatic candidiasis, trichomonas vaginalis, and symptomatic bacterial vaginosis; or cervical infection, including N. gonorrhoeae, C. trachomatis, or mucopurulent cervicitis; syphilis; herpes simplex virus lesions, or other sores (Note: seropositive herpes simplex virus without active lesions will not be excluded); acute pelvic inflammatory disease; urinary tract infection; recent exposure to a partner with N. gonorrhoeae, C. trachomatis, Trichomonas, syphilis, or non-gonorrheal urethritis
• Antibiotic or antifungal therapy (vaginal or systemic) within 7 days of enrollment
• As determined by the primary investigator, has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine \*including poorly controlled diabetes), respiratory, immunologic disorder or infectious disease
• Menses-like bleeding at the time of the Enrollment visit\* or expected menses-like bleeding within 14 days of the Enrollment visit (\*Women who have vaginal bleeding at the scheduled Enrollment visit may return at a different date to be re-examined and possibly enrolled provided they are still within the screening window and meet all criteria.)
• Any condition that, in the opinion of the Investigator, would preclude provision of consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Sponsors & Collaborators

• Hillier, Sharon, PhD: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Limitations and Caveats

After 25 participants were enrolled, 2 of 12 participants randomized to the low Eudragit® film arm had product discontinuations due to vaginal irritation and lack of product tolerability. The Protocol Safety Review Team voted to discontinue the low Eudragit® film arm resulting in only 12 participants of the 25 planned enrolled into that study arm. This limited the power of the study to detect significant differences in the outcomes between the two film arms.

Results Point of Contact

• Title: Dr. Leslie Meyn, Research Assistant Professor
• Organization: University of Pittsburgh

meynla@mwri.magee.edu

412-641-4233

Study Officials

• Katherine Bunge, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Sharon L Hillier, PhD

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 24, 2020
• Study Start: August 19, 2020
• Primary Completion: February 25, 2022
• Study Completion: October 10, 2022
• Last Updated: March 3, 2023
• Results First Posted: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)