Trial Outcomes & Findings for Single-Dose Study of MK-4250 Monotherapy in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-4250-002) (NCT NCT03351699)

NCT ID: NCT03351699

Last Updated: 2019-10-30

Results Overview

Plasma HIV-1 RNA was measured at Baseline and 168 hours after dosing. The log10 plasma HIV-RNA copies/mL measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. The change from Baseline in plasma HIV-1 RNA in participants administered MK-4250 was compared with historical placebo data.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

Baseline and Day 7

Results posted on

2019-10-30

Participant Flow

Participant milestones

Participant milestones
Measure
Panel A: MK-4250 150 mg
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Overall Study
STARTED
6
6
6
6
0
Overall Study
COMPLETED
6
6
6
6
0
Overall Study
NOT COMPLETED
0
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Single-Dose Study of MK-4250 Monotherapy in Anti-Retroviral Therapy-Naive, Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-4250-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Total
n=24 Participants
Total of all reporting groups
Age, Continuous
36.3 Years
STANDARD_DEVIATION 8.1 • n=5 Participants
32.5 Years
STANDARD_DEVIATION 6.1 • n=7 Participants
36.5 Years
STANDARD_DEVIATION 8.9 • n=5 Participants
35.5 Years
STANDARD_DEVIATION 7.3 • n=4 Participants
35.2 Years
STANDARD_DEVIATION 7.3 • n=8 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
6 Participants
n=7 Participants
6 Participants
n=5 Participants
6 Participants
n=4 Participants
0 Participants
n=21 Participants
24 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
1 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants
n=5 Participants
6 Participants
n=7 Participants
6 Participants
n=5 Participants
6 Participants
n=4 Participants
0 Participants
n=21 Participants
23 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
White
6 Participants
n=5 Participants
6 Participants
n=7 Participants
6 Participants
n=5 Participants
6 Participants
n=4 Participants
0 Participants
n=21 Participants
24 Participants
n=8 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
Baseline Plasma HIV-1 Ribonucleic Acid (RNA)
4.29394 log10 copies/mL
STANDARD_DEVIATION 0.41200 • n=5 Participants
4.42577 log10 copies/mL
STANDARD_DEVIATION 0.39577 • n=7 Participants
4.85677 log10 copies/mL
STANDARD_DEVIATION 0.23790 • n=5 Participants
4.42262 log10 copies/mL
STANDARD_DEVIATION 0.37308 • n=4 Participants
4.49978 log10 copies/mL
STANDARD_DEVIATION 0.40099 • n=8 Participants

PRIMARY outcome

Timeframe: Baseline and Day 7

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

Plasma HIV-1 RNA was measured at Baseline and 168 hours after dosing. The log10 plasma HIV-RNA copies/mL measurements from participants in each panel were pooled and analyzed based on a longitudinal data analysis model. The change from Baseline in plasma HIV-1 RNA in participants administered MK-4250 was compared with historical placebo data.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Change From Baseline in Plasma HIV-1 RNA Copies Per mL at 168 Hours
-1.56 log10 copies per mL
Interval -1.88 to -1.23
-1.76 log10 copies per mL
Interval -2.08 to -1.43
-1.55 log10 copies per mL
Interval -1.87 to -1.23
-1.78 log10 copies per mL
Interval -2.1 to -1.45

PRIMARY outcome

Timeframe: Up to Day 14

Population: Included all participants who received ≥1 dose of treatment. Panel F did not enroll because the scientific objectives were met following completion of Panel E.

The percentage of participants experiencing ≥1 AE was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=24 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
n=6 Participants
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Percentage of Participants Experiencing ≥1 Adverse Events (AE)
8.3 Percentage of Participants
83.3 Percentage of Participants
66.7 Percentage of Participants
83.3 Percentage of Participants
66.7 Percentage of Participants

PRIMARY outcome

Timeframe: Up to Day 14

Population: Included all participants who received ≥1 dose of treatment. Panel F did not enroll because the scientific objectives were met following completion of Panel E.

The percentage of participants who discontinued from the study due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=24 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
n=6 Participants
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Percentage of Participants Who Discontinued Study Due to an Adverse Event (AE)
0.0 Percentage of Participants
0.0 Percentage of Participants
0.0 Percentage of Participants
0.0 Percentage of Participants
0.0 Percentage of Participants

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Area Under the Concentration-Time Curve From 0 to Last Measurable Concentration (AUC0-last) for MK-4250
774 μM·hour
Geometric Coefficient of Variation 54
2040 μM·hour
Geometric Coefficient of Variation 17.1
2390 μM·hour
Geometric Coefficient of Variation 35
3860 μM·hour
Geometric Coefficient of Variation 44.3

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-4250
785 μM·hour
Geometric Coefficient of Variation 54.6
2120 μM·hour
Geometric Coefficient of Variation 18.4
2450 μM·hour
Geometric Coefficient of Variation 35.9
4010 μM·hour
Geometric Coefficient of Variation 47.6

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-4250
751 μM·Hour
Geometric Coefficient of Variation 52.6
1980 μM·Hour
Geometric Coefficient of Variation 16.7
2280 μM·Hour
Geometric Coefficient of Variation 34.1
3640 μM·Hour
Geometric Coefficient of Variation 41.2

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The maximum concentration (Cmax) of MK-4250 in plasma was observed.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Maximum Concentration (Cmax) of MK-4250 Reached in Plasma
16.6 μM
Geometric Coefficient of Variation 46.7
37.6 μM
Geometric Coefficient of Variation 26
43.5 μM
Geometric Coefficient of Variation 32.7
65 μM
Geometric Coefficient of Variation 25.8

SECONDARY outcome

Timeframe: 168 hours after administration of MK-4250.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The concentration of MK-4250 at 168 hours postdose (C168hr) was observed.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Concentration of MK-4250 at 168 Hours (C168hr)
0.558 μM
Geometric Coefficient of Variation 117
2.2 μM
Geometric Coefficient of Variation 57.4
2.38 μM
Geometric Coefficient of Variation 63.8
4.37 μM
Geometric Coefficient of Variation 96.4

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The apparent terminal half-life (t1/2) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Apparent Terminal Half-life (t1/2) of MK-4250
35.9 Hours
Geometric Coefficient of Variation 22.9
38.5 Hours
Geometric Coefficient of Variation 31.9
44.1 Hours
Geometric Coefficient of Variation 17.1
48.4 Hours
Geometric Coefficient of Variation 32.1

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The apparent clearance (CL/F) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Apparent Clearance (CL/F) of MK-4250
0.456 Liters/Hour
Geometric Coefficient of Variation 54.6
0.676 Liters/Hour
Geometric Coefficient of Variation 18.4
0.879 Liters/Hour
Geometric Coefficient of Variation 35.9
0.536 Liters/Hour
Geometric Coefficient of Variation 47.6

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The apparent volume of distribution (Vz/F) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Apparent Volume of Distribution (Vz/F) of MK-4250
23.6 Liters
Geometric Coefficient of Variation 45.1
37.6 Liters
Geometric Coefficient of Variation 23.5
56 Liters
Geometric Coefficient of Variation 31.7
37.4 Liters
Geometric Coefficient of Variation 17.5

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, 192, and 240 hours after administration of MK-4250. For Panel B only, the first three participants additionally had a 72-hour postdose time, and no 240-hour postdose time.

Population: All participants who complied with the protocol sufficiently to ensure data would likely exhibit the effects of treatment, according to the scientific model. Compliance included treatment exposure, measurement availability, and lack of major protocol deviations. Panel F did not enroll because the objectives were met following completion of Panel E.

The time to maximum concentration (Vz/F) of MK-4250 in plasma was calculated.

Outcome measures

Outcome measures
Measure
Panel A: MK-4250 150 mg
n=6 Participants
Participants received MK-4250 150 mg dose by mouth on Day 1 after an 8-hour fast.
Panel B: MK-4250 600 mg
n=6 Participants
Participants received MK-4250 600 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: MK-4250 900 mg
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: MK-4250 ≤900 mg With a Low-fat Meal
n=6 Participants
Participants received MK-4250 900 mg dose by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Panel F: MK-4250 ≤900 mg With a Moderate-fat Meal
Participants were to receive MK-4250 900 mg dose by mouth on Day 1 with a moderate-fat meal. The decision was made not to enroll Panel F because the scientific objectives were met following completion of Panel E.
Time to Maximum Concentration (Tmax) of MK-4250 Reached in Plasma
4.00 Hours
Interval 1.0 to 4.0
4.00 Hours
Interval 4.0 to 6.0
4.00 Hours
Interval 4.0 to 6.0
4.00 Hours
Interval 4.0 to 8.0

Adverse Events

Screening

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Panel A: 150 mg MK-4250

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Panel B: 600 mg MK-4250

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Panel D: 900 mg MK-4250

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Panel E: 900 mg MK-4250, With a Low Fat Meal

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Screening
n=24 participants at risk
This group represents all participants during their individual screening phase, approximately 4 weeks prior to first dose. No intervention was provided during this time.
Panel A: 150 mg MK-4250
n=6 participants at risk
Participants received MK-4250 150 mg tablet by mouth on Day 1 after an 8-hour fast.
Panel B: 600 mg MK-4250
n=6 participants at risk
Participants received MK-4250 600 mg tablet by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel B and the dose selected (i.e., ≤600 mg) was made based on evaluation of pharmacokinetics and 7-day safety and viral load data from Panel A.
Panel D: 900 mg MK-4250
n=6 participants at risk
Participants received MK-4250 900 mg tablet by mouth on Day 1 after an 8-hour fast. The decision to enroll Panel D was made upon completion of Panels A and B and evaluation of safety and viral load data from those panels.
Panel E: 900 mg MK-4250, With a Low Fat Meal
n=6 participants at risk
Participants received MK-4250 ≤900 mg tablet by mouth on Day 1 with a low-fat meal. The decision to enroll Panel E was made upon completion of Panel D and evaluation of safety and viral load data from that panel.
Blood and lymphatic system disorders
Lymphadenitis
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Gastrointestinal disorders
Abdominal pain
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Gastrointestinal disorders
Aphthous ulcer
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
33.3%
2/6 • Number of events 2 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Gastrointestinal disorders
Diarrhoea
0.00%
0/24 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
50.0%
3/6 • Number of events 3 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Gastrointestinal disorders
Dry mouth
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Gastrointestinal disorders
Nausea
0.00%
0/24 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Gastrointestinal disorders
Vomiting
0.00%
0/24 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
General disorders
Fatigue
0.00%
0/24 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Infections and infestations
Nasopharyngitis
0.00%
0/24 • Up to 6 weeks
50.0%
3/6 • Number of events 3 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Infections and infestations
Rhinitis
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Infections and infestations
Tonsillitis
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Musculoskeletal and connective tissue disorders
Bone pain
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
Nervous system disorders
Dizziness
0.00%
0/24 • Up to 6 weeks
33.3%
2/6 • Number of events 2 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Nervous system disorders
Headache
8.3%
2/24 • Number of events 2 • Up to 6 weeks
66.7%
4/6 • Number of events 4 • Up to 6 weeks
33.3%
2/6 • Number of events 2 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
50.0%
3/6 • Number of events 3 • Up to 6 weeks
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
0.00%
0/24 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Skin and subcutaneous tissue disorders
Acne
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.00%
0/24 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
Skin and subcutaneous tissue disorders
Pruritus
0.00%
0/24 • Up to 6 weeks
16.7%
1/6 • Number of events 1 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks
0.00%
0/6 • Up to 6 weeks

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Results disclosure agreements

  • Principal investigator is a sponsor employee Subsequent to the multicenter publication (or after public disclosure of the results at www.clinicaltrials.gov if multicenter manuscript is not planned), an investigator and colleagues may publish their data independently. Sponsor must have opportunity to review proposed abstracts, manuscripts or presentations 45 days prior to submission for publication/presentation. Confidential information must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
  • Publication restrictions are in place

Restriction type: OTHER