PharmacokineticsPhase 1FAME103NCT04319718
Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048
A Phase 1 study testing MK-2048 High Eudragit Vaginal Film and MK-2048 Low Eudragit Vaginal Film in people with Pharmacokinetics and Safety, run by Hillier, Sharon, PhD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics, Safety
- What is being tested?
- MK-2048 High Eudragit Vaginal Film and MK-2048 Low Eudragit Vaginal Film
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2020to 10 Oct 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Randomized, Double Blinded Study of the Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048
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.
Read the detailed description
This is a phase I randomized trial assessing the safety, acceptability, and pharmacokinetics of two formulations of MK-2048 vaginal film. While the primary objective is to evaluate the safety of the product, the overarching objective of this study is to provide proof of concept that an antiretroviral drug can be delivered in an extended release film formulation to provide drug delivery for 7 days or more after a single application. Forty eight women will be randomized with equal frequency to receive a single dose of a vaginal film containing MK-2048 (either the high Eudragit® or low Eudragit® formulation). The film will be inserted by a clinician on the day of enrollment. Vaginal swabs and plasma will be collected at days 0, 3, 5, 7, 10, 14 and 28 for all participants. On the day of enrollment, some participants may elect to participate in immediate post insertion sample collection (vaginal swab and plasma) at one or two time points within 6 hours of insertion. Genital biopsy samples and a rectal swab will be obtained on day 7, and cervicovaginal lavage will be collected at screening and days 14 and 28. The primary endpoint is the frequency of Grade 2 or higher adverse events. The secondary endpoints are: MK-2048 concentrations in plasma, cervical tissue homogenate, cervicovaginal lavage fluid, rectal and vaginal swab eluents; self-reported assessment of qualities of the experience with the films drawn from existing survey on microbicidal films, and general acceptability ratings drawn from market research methodology.
- Conditions
- Pharmacokinetics, Safety
- Being tested
- MK-2048 High Eudragit Vaginal Film, MK-2048 Low Eudragit Vaginal Film
- Keywords
- Vagina, Film, Extended Release
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-2048 High Eudragit Vaginal FilmCombination product
2" x 2" vaginal film containing 30 mg of MK-2048 and either 68.1 mg of ammonio methacrylate copolymer type B (Eudragit®)
MK-2048 Low Eudragit Vaginal FilmCombination product
2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
| Study group | Role | What they receive |
|---|---|---|
| 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®). Receives: 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®). Receives: Combination Product: MK-2048 Low Eudragit Vaginal Film |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grade 2 or Higher Adverse Events
Number of participants who experience Grade 2 or higher adverse events
Measured: Through study completion, approximately 28 days
Secondary outcomes (5)
Area Under the Plasma Concentration Versus Time Curve of MK-2048
Area under the plasma concentration versus time curve of MK-2048 reported as pg x day/mL. MK-2048 plasma concentration was measured at 0, 3, 5, 7, 10, 14, and 28 days after film insertion.
Measured: Through study completion, approximately 28 days
Area Under the Cervical Tissue Homogenate Concentration Versus Time Curve of MK-2048
Area under the cervical tissue homogenate concentration versus time curve of MK-2048 reported as pg x day/mL. MK-2048 concentration was measured at 0, 3, 5, 7, 10, 14, and 28 days after film insertion.
Measured: Through study completion, approximately 28 days
Area Under the Cervicovaginal Lavage Fluid Concentration Versus Time Curve of MK-2048
Area under the cervicovaginal lavage fluid concentration versus time curve of MK-2048 reported as pg x day/mL
Measured: Through study completion, approximately 28 days
Area Under the Rectal Swab Eluent Concentration Versus Time Curve of MK-2048
Area under the rectal swab eluent concentration versus time curve of MK-2048 reported as pg x day/mL
Measured: Through study completion, approximately 28 days
Area Under the Vaginal Swab Eluent Concentration Versus Time Curve of MK-2048
Area under the vaginal swab eluent concentration versus time curve of MK-2048 reported as ng x day/mL. MK-2048 concentration was measured at 0, 3, 5, 7, 10, 14, and 28 days after film insertion.
Measured: Through study completion, approximately 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2020
- Study start19 Aug 2020
- Primary completion25 Feb 2022
- Study completion10 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hillier, Sharon, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katherine Bunge, University of Pittsburgh
- Investigators
- Katherine Bunge, MD, Principal investigator, University of PittsburghSharon L Hillier, PhD, Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04319718
- Sponsor's protocol ID
- STUDY19100120
- Other IDs
- 1U19AI120249
- Acronym
- FAME103
- Status last verified
- Mar 2023
- First submitted
- 17 Mar 2020
- Last updated
- 3 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blinded Study of the Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048
- ClinicalTrials.gov ID
- NCT04319718
- Acronym / sponsor ID
- FAME103 / STUDY19100120
- Conditions
- Pharmacokinetics, Safety
- Keywords
- Vagina, Film, Extended Release
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Hillier, Sharon, PhDUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- 25 Feb 2022 (actual)
- Study completion
- 10 Oct 2022 (actual)
- First posted
- 24 Mar 2020 (actual)
- Results
- Posted 3 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase I randomized trial assessing the safety, acceptability, and pharmacokinetics of two formulations of MK-2048 vaginal film. While the primary objective is to evaluate the safety of the product, the overarching objective of this study is to provide proof of concept that an antiretroviral drug can be delivered in an extended release film formulation to provide drug delivery for 7 days or more after a single application. Forty eight women will be randomized with equal frequency to receive a single dose of a vaginal film containing MK-2048 (either the high Eudragit® or low Eudragit® formulation). The film will be inserted by a clinician on the day of enrollment. Vaginal swabs and plasma will be collected at days 0, 3, 5, 7, 10, 14 and 28 for all participants. On the day of enrollment, some participants may elect to participate in immediate post insertion sample collection (vaginal swab and plasma) at one or two time points within 6 hours of insertion. Genital biopsy samples and a rectal swab will be obtained on day 7, and cervicovaginal lavage will be collected at screening and days 14 and 28. The primary endpoint is the frequency of Grade 2 or higher adverse events. The secondary endpoints are: MK-2048 concentrations in plasma, cervical tissue homogenate, cervicovaginal lavage fluid, rectal and vaginal swab eluents; self-reported assessment of qualities of the experience with the films drawn from existing survey on microbicidal films, and general acceptability ratings drawn from market research methodology.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Eudragit MK-2048 vaginal film | Active comparator | Combination Product: MK-2048 High Eudragit Vaginal FilmSingle use of 2" x 2" vaginal film containing 30 mg of MK-2048 and 68.1 mg of ammonio methacrylate copolymer type B (Eudragit®). |
| Low Eudragit MK-2048 vaginal film | Active comparator | Combination Product: MK-2048 Low Eudragit Vaginal FilmSingle use of 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- Menopause (as defined as amenorrhea for one year or more without an alternative etiology)
- Hysterectomy
- Participant report of any of the following:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-2048 High Eudragit Vaginal Film2" x 2" vaginal film containing 30 mg of MK-2048 and either 68.1 mg of ammonio methacrylate copolymer type B (Eudragit®) | Combination product | High Eudragit MK-2048 vaginal film |
| MK-2048 Low Eudragit Vaginal Film2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®) | Combination product | Low Eudragit MK-2048 vaginal film |
Primary outcome
Number of Participants With Grade 2 or Higher Adverse Events
Time frame: Through study completion, approximately 28 days
Number of participants who experience Grade 2 or higher adverse events
5 secondary outcomes
Area Under the Plasma Concentration Versus Time Curve of MK-2048
Time frame: Through study completion, approximately 28 days
Area Under the Cervical Tissue Homogenate Concentration Versus Time Curve of MK-2048
Time frame: Through study completion, approximately 28 days
Area Under the Cervicovaginal Lavage Fluid Concentration Versus Time Curve of MK-2048
Time frame: Through study completion, approximately 28 days
Area Under the Rectal Swab Eluent Concentration Versus Time Curve of MK-2048
Time frame: Through study completion, approximately 28 days
Area Under the Vaginal Swab Eluent Concentration Versus Time Curve of MK-2048
Time frame: Through study completion, approximately 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Pharmacokinetics
RecruitingObservational study
Population Pharmacokinetics of Temocillin in Acute Enterobacterial Pyelonephritis in Children
Pyelonephritis
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Bunge, MD principal investigator
University of Pittsburgh
Sharon L Hillier, PhD study chair
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-2048 High Eudragit Vaginal Film and MK-2048 Low Eudragit Vaginal Film in people with Pharmacokinetics and Safety, run by Hillier, Sharon, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade 2 or Higher Adverse Events (time frame: Through study completion, approximately 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2023.