Trial Outcomes & Findings for Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048 (NCT NCT04319718)

NCT ID: NCT04319718

Last Updated: 2023-03-03

Results Overview

Number of participants who experience Grade 2 or higher adverse events

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 37 participants
• Primary outcome timeframe: Through study completion, approximately 28 days
• Results posted on: 2023-03-03

Participant Flow

Participant milestones

Measure	High Eudragit MK-2048 Vaginal Film 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®). MK-2048 High Eudragit Vaginal Film: 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 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Overall Study STARTED	25	12
Overall Study COMPLETED	24	10
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	High Eudragit MK-2048 Vaginal Film 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®). MK-2048 High Eudragit Vaginal Film: 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 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Overall Study Adverse Event	0	2
Overall Study Cervical biopsy not performed since participant did not refrain from sexual activity	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	High Eudragit MK-2048 Vaginal Film n=25 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=12 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)	Total n=37 Participants Total of all reporting groups
Age, Continuous	26.6 years STANDARD_DEVIATION 6.9 • n=5 Participants	28.2 years STANDARD_DEVIATION 5.5 • n=7 Participants	27.2 years STANDARD_DEVIATION 6.5 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	12 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic, white	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic, white	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic, black	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Bi-/multi-racial	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic, not otherwise specified	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	12 participants n=7 Participants	37 participants n=5 Participants
Has current sexual partner	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through study completion, approximately 28 days

Number of participants who experience Grade 2 or higher adverse events

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=25 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=12 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Number of Participants With Grade 2 or Higher Adverse Events	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Through study completion, approximately 28 days

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.

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=25 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=12 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Area Under the Plasma Concentration Versus Time Curve of MK-2048	1370 pg x day/mL Interval 706.0 to 2435.0	1873 pg x day/mL Interval 563.0 to 3959.0

SECONDARY outcome

Timeframe: Through study completion, approximately 28 days

Population: MK 2048 levels in all tissue homogenate samples were below the limit of quantitation for the assay. Therefore, the area under the curve could not be calculated.

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.

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=25 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=12 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Area Under the Cervical Tissue Homogenate Concentration Versus Time Curve of MK-2048	NA pg x day/mL MK 2048 levels in all tissue homogenate samples were below the limit of quantitation for the assay.	NA pg x day/mL MK 2048 levels in all tissue homogenate samples were below the limit of quantitation for the assay.

SECONDARY outcome

Timeframe: Through study completion, approximately 28 days

Population: Data not collected

Area under the cervicovaginal lavage fluid concentration versus time curve of MK-2048 reported as pg x day/mL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, approximately 28 days

Population: Data not collected

Area under the rectal swab eluent concentration versus time curve of MK-2048 reported as pg x day/mL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, approximately 28 days

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.

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=25 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=12 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Area Under the Vaginal Swab Eluent Concentration Versus Time Curve of MK-2048	543608 ng x day/mL Interval 50535.0 to 3256911.0	1112355 ng x day/mL Interval 58319.0 to 1642201.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Through study completion, approximately 28 days

Population: All participants with a cervical biopsy sample taken. Two participants in the low Eudragit arm did not have cervical biopsies performed due to product discontinuation. One participant in the high arm also did not have a cervical biopsy collected due to safety concerns since she did not refrain from sexual activity prior to the visit.

Median fold change in in-vitro anti-human immunodeficiency virus-1 activity in cervicovaginal lavage fluid determined by the TZM-bl assay and defined as percent inhibition of human immunodeficiency virus-1 infection by luciferase for a single round of replication measured at day 28 divided by percent inhibition measured at baseline.

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=24 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=10 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Median Fold Change in Percent Inhibition of Human Immunodeficiency Virus-1 Replication in Cervicovaginal Lavage Fluid	1.01 ratio Interval 0.13 to 1.25	.92 ratio Interval 0.09 to 1.11

OTHER_PRE_SPECIFIED outcome

Timeframe: Through study completion, approximately 28 days

Population: All participants with a cervical biopsy sample taken. Two participants in the low Eudragit arm did not have cervical biopsies performed due to product discontinuation. One participant in the high Eudragit arm did not have a cervical biopsy collected due to safety concerns since she did not remain sexually abstinence prior to the visit and one participant's biopsy p24 results are not evaluable due to a lab processing error.

Human Immunodeficiency Virus-1 infection of cervical biopsies as defined as titer of the HIV-1 p24 core protein measured by ELISA and expressed as log10 pg/mL per mg of tissue

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=23 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=10 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Human Immunodeficiency Virus-1 p24 Core Protein Titer in Cervical Biopsies	96.0 log10 pg/mL Interval 17.1 to 1210.5	543.5 log10 pg/mL Interval 265.0 to 9050.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Through study completion, approximately 28 days

Population: All participants who had Nugent scores assessed at enrollment and at one or more follow-up visits. The 2 women who discontinued product in the low Eudragit arm were only followed for safety and did not have urogenital samples collected beyond the enrollment visit.

Mean change in the Nugent score as determined from vaginal smears. Nugent scores range from 0 to 10; 0 indicates a Lactobacillus-dominant microbiome while a score of 10 indicates a microbiome dominated by bacterial vaginosis-associated bacteria. Nugent scores were assessed at 0, 3, 5, 7, 10, 14, and 28 days after film insertion. The mean change was estimated from a mixed effects linear regression model and is defined as the average change between each post-insertion time point and the pre-insertion time point.

Outcome measures

Measure	High Eudragit MK-2048 Vaginal Film n=25 Participants 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®). MK-2048 High Eudragit Vaginal Film: 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 n=10 Participants 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Mean Change in Nugent Score	-0.35 units on a scale Interval -0.93 to 0.24	-0.62 units on a scale Interval -1.71 to 0.48

Adverse Events

High Eudragit MK-2048 Vaginal Film

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Low Eudragit MK-2048 Vaginal Film

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	High Eudragit MK-2048 Vaginal Film n=25 participants at risk 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®). MK-2048 High Eudragit Vaginal Film: 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 n=12 participants at risk 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®). MK-2048 Low Eudragit Vaginal Film: 2" x 2" vaginal film containing 30 mg of MK-2048 and 41.5 mg of ammonio methacrylate copolymer type B (Eudragit®)
Reproductive system and breast disorders Abnormal vaginal discharge	32.0% 8/25 • Number of events 8 • 1 month	41.7% 5/12 • Number of events 5 • 1 month
Reproductive system and breast disorders Vulvovaginal itching	20.0% 5/25 • Number of events 5 • 1 month	33.3% 4/12 • Number of events 4 • 1 month
Reproductive system and breast disorders Unexpected vaginal bleeding	12.0% 3/25 • Number of events 3 • 1 month	33.3% 4/12 • Number of events 4 • 1 month
Reproductive system and breast disorders Vulvovaginal irritation	8.0% 2/25 • Number of events 2 • 1 month	8.3% 1/12 • Number of events 1 • 1 month
Infections and infestations Bacterial vaginosis	0.00% 0/25 • 1 month	16.7% 2/12 • Number of events 2 • 1 month
Reproductive system and breast disorders Vaginal odor	8.0% 2/25 • Number of events 2 • 1 month	0.00% 0/12 • 1 month
Reproductive system and breast disorders Early menses	0.00% 0/25 • 1 month	8.3% 1/12 • Number of events 1 • 1 month
Reproductive system and breast disorders Vaginal dryness	0.00% 0/25 • 1 month	8.3% 1/12 • Number of events 1 • 1 month
Musculoskeletal and connective tissue disorders Back pain, low	0.00% 0/25 • 1 month	8.3% 1/12 • Number of events 1 • 1 month
Psychiatric disorders Post-traumatic stress disorder, worsening	0.00% 0/25 • 1 month	8.3% 1/12 • Number of events 1 • 1 month

Additional Information

Dr. Leslie Meyn, Research Assistant Professor

University of Pittsburgh

Phone: 412-641-4233

Email: meynla@mwri.magee.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place