Trial Outcomes & Findings for Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy and Hepatitis C Infected Male Participants (MK-3281-002) (NCT NCT00635804)

Last Updated: 2018-09-05

Results Overview

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

Up to 14 days after the last dose of study drug (up to 24 days maximum)

Results posted on

2018-09-05

Participant Flow

Panel H, planned for GT1a/GT1b HCV-infected male participants to receive 400 mg MK-3281 orally BID for 7 consecutive days, did not enroll any participants. As pre-specified by the protocol, it was possible that some panels would not be enrolled if study objectives were met with prior doses.

60 participants were enrolled in this study and received MK-3281 or placebo in Panels A through G.

Participant milestones

Participant milestones
Measure	Pt 1: MK-3281 100 mg BID (Panel A) Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Overall Study STARTED	7	6	6	6	6	12	3	14
Overall Study COMPLETED	6	6	6	6	6	11	3	14
Overall Study NOT COMPLETED	1	0	0	0	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Pt 1: MK-3281 100 mg BID (Panel A) Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Overall Study Adverse Event	0	0	0	0	0	1	0	0
Overall Study Withdrawal by Subject	1	0	0	0	0	0	0	0

Baseline Characteristics

Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-3281 in Healthy and Hepatitis C Infected Male Participants (MK-3281-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=7 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo n=14 Participants Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).	Total n=60 Participants Total of all reporting groups
Age, Continuous	37.1 years STANDARD_DEVIATION 8.7 • n=5 Participants	36.3 years STANDARD_DEVIATION 13.5 • n=7 Participants	37.0 years STANDARD_DEVIATION 13.0 • n=5 Participants	34.0 years STANDARD_DEVIATION 14.9 • n=4 Participants	39.2 years STANDARD_DEVIATION 7.3 • n=21 Participants	47.5 years STANDARD_DEVIATION 8.8 • n=10 Participants	45.0 years STANDARD_DEVIATION 5.2 • n=115 Participants	39.4 years STANDARD_DEVIATION 10.0 • n=6 Participants	39.9 years STANDARD_DEVIATION 10.9 • n=6 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=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	12 Participants n=10 Participants	3 Participants n=115 Participants	14 Participants n=6 Participants	60 Participants n=6 Participants

PRIMARY outcome

Timeframe: Up to 14 days after the last dose of study drug (up to 24 days maximum)

Population: All Treated Participants

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=7 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo n=14 Participants Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Number of Participants Experiencing Adverse Events (AEs)	5 participants	3 participants	4 participants	5 participants	3 participants	12 participants	2 participants	12 participants

PRIMARY outcome

Timeframe: Up to 14 days after the last dose of study drug (up to 24 days maximum)

Population: All Treated Participants

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=7 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo n=14 Participants Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Number of Participants Who Discontinued Study Medication Due to AEs	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Predose daily on Days 2-9 (for healthy participants) and Days 2-6 (for HCV+ participants), and predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 1, Day 7 (HCV+ participants), and Day 10 (healthy participants)

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and MK-3281 AUC(0-12) was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 Day 1	4.92 μM·hr Geometric Coefficient of Variation 39.9	12.39 μM·hr Geometric Coefficient of Variation 36.2	13.21 μM·hr Geometric Coefficient of Variation 45.0	18.12 μM·hr Geometric Coefficient of Variation 70.9	12.78 μM·hr Geometric Coefficient of Variation 22.4	11.36 μM·hr Geometric Coefficient of Variation 47.7	12.01 μM·hr Geometric Coefficient of Variation 27.5	—
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 Day 7	NA μM·hr Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM·hr Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM·hr Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM·hr Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	61.08 μM·hr Geometric Coefficient of Variation 20.1	51.68 μM·hr Geometric Coefficient of Variation 29.8	88.21 μM·hr Geometric Coefficient of Variation 37.0	—
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 Day 10	11.51 μM·hr Geometric Coefficient of Variation 31.7	29.71 μM·hr Geometric Coefficient of Variation 32.1	37.21 μM·hr Geometric Coefficient of Variation 22.6	67.11 μM·hr Geometric Coefficient of Variation 28.1	NA μM·hr Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	NA μM·hr Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	NA μM·hr Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	—

SECONDARY outcome

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and MK-3281 Cmax was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Maximum Plasma Concentration (Cmax) of MK-3281 Day 1	0.74 μM Geometric Coefficient of Variation 32.6	1.75 μM Geometric Coefficient of Variation 39.1	1.80 μM Geometric Coefficient of Variation 48.3	2.73 μM Geometric Coefficient of Variation 75.9	1.61 μM Geometric Coefficient of Variation 24.9	1.60 μM Geometric Coefficient of Variation 43.7	1.69 μM Geometric Coefficient of Variation 28.4	—
Maximum Plasma Concentration (Cmax) of MK-3281 Day 7	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	6.78 μM Geometric Coefficient of Variation 23.9	5.60 μM Geometric Coefficient of Variation 33.3	10.73 μM Geometric Coefficient of Variation 40.5	—
Maximum Plasma Concentration (Cmax) of MK-3281 Day 10	1.28 μM Geometric Coefficient of Variation 28.3	3.45 μM Geometric Coefficient of Variation 36.2	4.97 μM Geometric Coefficient of Variation 44.1	7.83 μM Geometric Coefficient of Variation 48.8	NA μM Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	NA μM Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	NA μM Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	—

SECONDARY outcome

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and MK-3281 plasma C12hr was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
12-Hour Concentration of MK-3281 in Plasma (C12hr) Day 1	0.26 μM Geometric Coefficient of Variation 42.3	0.61 μM Geometric Coefficient of Variation 35.2	0.70 μM Geometric Coefficient of Variation 40.5	0.95 μM Geometric Coefficient of Variation 73.1	0.76 μM Geometric Coefficient of Variation 29.7	0.64 μM Geometric Coefficient of Variation 66.1	0.64 μM Geometric Coefficient of Variation 26.6	—
12-Hour Concentration of MK-3281 in Plasma (C12hr) Day 7	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	NA μM Geometric Coefficient of Variation NA This group was not assessed for PK on this day.	3.62 μM Geometric Coefficient of Variation 25.7	3.09 μM Geometric Coefficient of Variation 26.9	4.90 μM Geometric Coefficient of Variation 32.1	—
12-Hour Concentration of MK-3281 in Plasma (C12hr) Day 10	0.64 μM Geometric Coefficient of Variation 40.3	1.66 μM Geometric Coefficient of Variation 32.1	1.86 μM Geometric Coefficient of Variation 26.3	2.87 μM Geometric Coefficient of Variation 24.2	NA μM Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	NA μM Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	NA μM Geometric Coefficient of Variation NA This group did not receive MK-3281 on this day.	—

SECONDARY outcome

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and MK-3281 Tmax was calculated at Days 1 and 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Time To Reach Cmax (Tmax) of MK-3281 Day 1	3.0 hour Full Range 42.3 • Interval 1.5 to 6.0	2.0 hour Full Range 35.2 • Interval 1.5 to 3.0	5.0 hour Full Range 40.5 • Interval 3.0 to 6.0	3.0 hour Full Range 73.1 • Interval 1.5 to 4.0	2.5 hour Full Range 29.7 • Interval 1.4 to 4.0	3.0 hour Full Range 66.1 • Interval 1.5 to 6.0	3.0 hour Full Range 26.6 • Interval 3.0 to 3.1	—
Time To Reach Cmax (Tmax) of MK-3281 Day 7	NA hour Full Range NA This group was not assessed for PK on this day.	NA hour Full Range NA This group was not assessed for PK on this day.	NA hour Full Range NA This group was not assessed for PK on this day.	NA hour Full Range NA This group was not assessed for PK on this day.	2.3 hour Full Range 25.7 • Interval 0.0 to 2.8	2.0 hour Full Range 26.9 • Interval 1.0 to 3.0	1.0 hour Full Range 32.1 • Interval 0.0 to 1.5	—
Time To Reach Cmax (Tmax) of MK-3281 Day 10	3.5 hour Full Range 40.3 • Interval 2.0 to 4.0	3.0 hour Full Range 32.1 • Interval 2.0 to 4.0	3.5 hour Full Range 26.3 • Interval 1.5 to 6.0	3.0 hour Full Range 24.2 • Interval 1.5 to 4.0	NA hour Full Range NA This group did not receive MK-3281 on this day.	NA hour Full Range NA This group did not receive MK-3281 on this day.	NA hour Full Range NA This group did not receive MK-3281 on this day.	—

SECONDARY outcome

Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours post-dose on Day 7 (HCV+ participants) or Day 10 (healthy participants)

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and MK-3281 apparent t ½ was calculated at Day 7 (for HCV+ participants) or Day 10 (for healthy participants) using the MK-3281 assay. Harmonic mean t ½ and pseudo standard deviation were reported.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Apparent Half-Life (t ½) of MK-3281 Day 7	NA hour Standard Deviation NA This group was not assessed for PK on this day.	NA hour Standard Deviation NA This group was not assessed for PK on this day.	NA hour Standard Deviation NA This group was not assessed for PK on this day.	NA hour Standard Deviation NA This group was not assessed for PK on this day.	18.3 hour Standard Deviation 4.0	19.7 hour Standard Deviation 3.3	19.5 hour Standard Deviation 2.0	—
Apparent Half-Life (t ½) of MK-3281 Day 10	17.2 hour Standard Deviation 2.3	17.5 hour Standard Deviation 2.9	17.4 hour Standard Deviation 2.5	16.9 hour Standard Deviation 1.3	NA hour Standard Deviation NA This group did not receive MK-3281 on Day 10, thus this day was not used to calculate t 1/2.	NA hour Standard Deviation NA This group did not receive MK-3281 on Day 10, thus this day was not used to calculate t 1/2.	NA hour Standard Deviation NA This group did not receive MK-3281 on Day 10, thus this day was not used to calculate t 1/2.	—

SECONDARY outcome

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and the MK-3281 AUC(0-12hr) accumulation ratio was calculated for HCV+ participants and healthy participants. AUC(0-12hr) accumulation ratio calculated for healthy participants as Day 10 AUC (0-12hr) / Day 1 AUC (0-12hr). AUC(0-12hr) accumulation ratio calculated for HCV+ participants as Day 7 AUC (0-12hr) / Day 1 AUC (0-12hr).

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
AUC (0-12hr) Accumulation Ratio of MK-3281	2.3 ratio 90% Confidence Interval NA • Interval 1.6 to 3.4	2.4 ratio 90% Confidence Interval NA • Interval 1.6 to 3.5	2.8 ratio 90% Confidence Interval NA • Interval 1.9 to 4.1	3.7 ratio 90% Confidence Interval NA • Interval 2.5 to 5.6	4.8 ratio 90% Confidence Interval 4.0 • Interval 3.6 to 6.4	4.5 ratio 90% Confidence Interval 3.3 • Interval 3.7 to 5.6	7.3 ratio 90% Confidence Interval 2.0 • Interval 4.9 to 11.1	—

SECONDARY outcome

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and the MK-3281 Cmax accumulation ratio was calculated for HCV+ participants and healthy participants. Cmax accumulation ratio calculated for healthy participants as Day 10 Cmax / Day 1 Cmax. Cmax accumulation ratio calculated for HCV+ participants as Day 7 Cmax / Day 1 Cmax.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Cmax Accumulation Ratio of MK-3281	1.7 ratio 90% Confidence Interval NA • Interval 1.2 to 2.6	2.0 ratio 90% Confidence Interval NA • Interval 1.3 to 3.0	2.8 ratio 90% Confidence Interval NA • Interval 1.8 to 4.2	2.9 ratio 90% Confidence Interval NA • Interval 1.9 to 4.4	4.2 ratio 90% Confidence Interval 4.0 • Interval 3.0 to 5.9	3.5 ratio 90% Confidence Interval 3.3 • Interval 2.7 to 4.4	6.4 ratio 90% Confidence Interval 2.0 • Interval 4.0 to 10.1	—

SECONDARY outcome

Population: All Treated Participants with available PK data. Participants in the Placebo group did not receive MK-3281 and therefore did not have PK data reported.

Blood samples were obtained from participants and the MK-3281 C12hr accumulation ratio was calculated for HCV+ participants and healthy participants. C12hr accumulation ratio calculated for healthy participants as Day 10 C12hr / Day 1 C12hr. C12hr accumulation ratio calculated for HCV+ participants as Day 7 C12hr / Day 1 C12hr.

Outcome measures

Outcome measures
Measure	Pt 1: MK-3281 100 mg BID (Panel A) n=6 Participants Healthy male participants in this Part I serial panel receive 100 mg MK-3281 orally twice daily (BID) for 10 consecutive days for a total daily dose administered of 200 mg. The evening (PM) dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 200 mg BID (Panel B) n=6 Participants Healthy male participants in this Part I serial panel receive 200 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 400 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 400 mg BID (Panel C) n=6 Participants Healthy male participants in this Part I serial panel receive 400 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 800 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 1: MK-3281 800 mg BID (Panel D) n=6 Participants Healthy male participants in this Part I serial panel receive 800 mg MK-3281 orally BID for 10 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 10.	Pt 2: MK-3281 800 mg BID (Panel E) n=6 Participants Genotype (GT)1 Hepatitis C Virus (HCV)-infected male participants in this Part II serial panel received 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 800 mg BID (Panel F) n=12 Participants GT1a/GT1-nontypeable/GT3/GT1b HCV-infected male participants in this Part II serial panel receive 800 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 1600 mg. The PM dose of MK-3281 was not administered on Day 7.	Pt 2: MK-3281 1200 mg BID (Panel G) n=3 Participants GT1a (and/or GT1 nontypeable) and GT1b HCV-infected male participants in this Part II serial panel receive 1200 mg MK-3281 orally BID for 7 consecutive days for a total daily dose administered of 2400 mg. The PM dose of MK-3281 was not administered on Day 7.	Placebo Participants receive dose-matched placebo to MK-03281 orally BID for 7 or 10 consecutive days depending on randomization. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
C12hr Accumulation Ratio of MK-3281	2.5 ratio 90% Confidence Interval NA • Interval 1.6 to 4.1	2.7 ratio 90% Confidence Interval NA • Interval 1.7 to 4.4	2.6 ratio 90% Confidence Interval NA • Interval 1.6 to 4.3	3.0 ratio 90% Confidence Interval NA • Interval 1.9 to 4.9	4.7 ratio 90% Confidence Interval 4.0 • Interval 3.6 to 6.2	4.8 ratio 90% Confidence Interval 3.3 • Interval 4.0 to 5.8	7.7 ratio 90% Confidence Interval 2.0 • Interval 5.3 to 11.2	—

SECONDARY outcome

Timeframe: Baseline (pre-dose Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7

Population: Treated HCV+ participants in Part II with available HCV RNA data. 800 mg dose group contained members of Panels E and F. No healthy participants from Part 1 (Panels A, B, C, or D) were assessed for this outcome measure.

For evaluation of MK-3281 antiviral activity, the maximum reduction in HCV ribonucleic acid (RNA) levels over the course of the study was assessed by MK-3281 dose group in HCV+ participants and the mean maximum viral load reduction was summarized. HCV RNA levels were measured at predose and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours postdose on Day 1 and Day 7; pre-morning (AM) and pre-evening (PM) dose Day 2; and pre AM dose Days 3-6. For each participant, baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing, and change from baseline (difference) was calculated at each time point. The response for that participant was defined as: - (postbaseline time point - baseline) at the time point with the lowest HCV RNA level.