Hepatitis C
Conditions
Brief summary
This study will examine the safety, tolerability and plasma pharmacokinetics of multiple doses of MK-3281 in healthy male participants in Part I, and in Hepatitis C Virus (HCV)-infected male participants in Part II. The clinical efficacy of MK-3281, as measured by viral load reduction, will also be assessed in Part II. The primary hypothesis is that twice daily administration of MK-3281 for 10 days in healthy adult male participants and for 7 days in HCV-infected male participants is sufficiently safe and well tolerated, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation. The results of this study will guide dose selection for future studies in both healthy participants and HCV-infected participants.
Interventions
DRUGMK-3281
MK-3281 capsule administered orally BID for 7 or 10 consecutive days depending on randomized dose. The PM dose of MK-3281 was not administered on Day 7 (for HCV-infected males) or Day 10 (for healthy males)
DRUGPlacebo to MK-3281
Dose-matched placebo to MK-3281 capsule administered orally BID for 7 or 10 consecutive days depending on randomized dose of MK-3281 in serial panel. The PM dose of matched placebo was not administered on Day 7 or 10 (depending upon allocation).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant is judged to be in good/stable health based on medical history, physical examination, vital signs, and laboratory safety tests performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug * Participant has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug * Participants with female partner(s) of childbearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug * Participant has a clinical diagnosis of chronic HCV infection (for Part II only).
Exclusion criteria
* Participant has a history of stroke, chronic seizures, or major neurological disorder * Participant has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases * Participant has a history of neoplastic disease (including leukemia, lymphoma, malignant melanoma), or myeloproliferative disease, regardless of the time since treatment * Participant has positive Hepatitis B surface antigen (or other evidence of active Hepatitis B infection) at the prescreening (study) visit * For Healthy Panel (Part I), participant has evidence of chronic Hepatitis C virus infection at the prescreening (study) visit * Participant has a history of documented Human Immunodeficiency Virus (HIV) infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Adverse Events (AEs) | Up to 14 days after the last dose of study drug (up to 24 days maximum) | 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. |
| Number of Participants Who Discontinued Study Medication Due to AEs | Up to 14 days after the last dose of study drug (up to 24 days maximum) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 12-Hour Concentration of MK-3281 in Plasma (C12hr) | 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) | 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. |
| Time To Reach Cmax (Tmax) of MK-3281 | 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) | 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. |
| Apparent Half-Life (t ½) of MK-3281 | 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) | 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. |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | 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) | 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. |
| Cmax Accumulation Ratio of MK-3281 | 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) | 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. |
| C12hr Accumulation Ratio of MK-3281 | 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) | 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. |
| Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days | Baseline (pre-dose Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 | 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. |
| AUC (0-12hr) Accumulation Ratio of MK-3281 | 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) | 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). |
| Maximum Plasma Concentration (Cmax) of MK-3281 | 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) | 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. |
Participant flow
Recruitment details
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.
Pre-assignment details
60 participants were enrolled in this study and received MK-3281 or placebo in Panels A through G.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 12 |
| 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. | 3 |
| 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). | 14 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| 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
| Characteristic | Pt 1: MK-3281 100 mg BID (Panel A) | Pt 1: MK-3281 200 mg BID (Panel B) | Pt 1: MK-3281 400 mg BID (Panel C) | Pt 1: MK-3281 800 mg BID (Panel D) | Pt 2: MK-3281 800 mg BID (Panel E) | Pt 2: MK-3281 800 mg BID (Panel F) | Pt 2: MK-3281 1200 mg BID (Panel G) | Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 8.7 | 36.3 years STANDARD_DEVIATION 13.5 | 37.0 years STANDARD_DEVIATION 13 | 34.0 years STANDARD_DEVIATION 14.9 | 39.2 years STANDARD_DEVIATION 7.3 | 47.5 years STANDARD_DEVIATION 8.8 | 45.0 years STANDARD_DEVIATION 5.2 | 39.4 years STANDARD_DEVIATION 10 | 39.9 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 3 Participants | 14 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 3 / 6 | 4 / 6 | 5 / 6 | 3 / 6 | 12 / 12 | 2 / 3 | 12 / 14 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 3 | 0 / 14 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events (AEs)
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.
Time frame: Up to 14 days after the last dose of study drug (up to 24 days maximum)
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | Number of Participants Experiencing Adverse Events (AEs) | 5 participants |
| Pt 1: MK-3281 200 mg BID (Panel B) | Number of Participants Experiencing Adverse Events (AEs) | 3 participants |
| Pt 1: MK-3281 400 mg BID (Panel C) | Number of Participants Experiencing Adverse Events (AEs) | 4 participants |
| Pt 1: MK-3281 800 mg BID (Panel D) | Number of Participants Experiencing Adverse Events (AEs) | 5 participants |
| Pt 2: MK-3281 800 mg BID (Panel E) | Number of Participants Experiencing Adverse Events (AEs) | 3 participants |
| Pt 2: MK-3281 800 mg BID (Panel F) | Number of Participants Experiencing Adverse Events (AEs) | 12 participants |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Number of Participants Experiencing Adverse Events (AEs) | 2 participants |
| Placebo | Number of Participants Experiencing Adverse Events (AEs) | 12 participants |
Primary
Number of Participants Who Discontinued Study Medication Due to AEs
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.
Time frame: Up to 14 days after the last dose of study drug (up to 24 days maximum)
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
| Pt 1: MK-3281 200 mg BID (Panel B) | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
| Pt 1: MK-3281 400 mg BID (Panel C) | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
| Pt 1: MK-3281 800 mg BID (Panel D) | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
| Pt 2: MK-3281 800 mg BID (Panel E) | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
| Pt 2: MK-3281 800 mg BID (Panel F) | Number of Participants Who Discontinued Study Medication Due to AEs | 1 participants |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
| Placebo | Number of Participants Who Discontinued Study Medication Due to AEs | 0 participants |
Secondary
12-Hour Concentration of MK-3281 in Plasma (C12hr)
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | 0.64 μM | Geometric Coefficient of Variation 40.3 |
| Pt 1: MK-3281 100 mg BID (Panel A) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | NA μM | — |
| Pt 1: MK-3281 100 mg BID (Panel A) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.26 μM | Geometric Coefficient of Variation 42.3 |
| Pt 1: MK-3281 200 mg BID (Panel B) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | NA μM | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.61 μM | Geometric Coefficient of Variation 35.2 |
| Pt 1: MK-3281 200 mg BID (Panel B) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | 1.66 μM | Geometric Coefficient of Variation 32.1 |
| Pt 1: MK-3281 400 mg BID (Panel C) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | 1.86 μM | Geometric Coefficient of Variation 26.3 |
| Pt 1: MK-3281 400 mg BID (Panel C) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.70 μM | Geometric Coefficient of Variation 40.5 |
| Pt 1: MK-3281 400 mg BID (Panel C) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | NA μM | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | NA μM | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.95 μM | Geometric Coefficient of Variation 73.1 |
| Pt 1: MK-3281 800 mg BID (Panel D) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | 2.87 μM | Geometric Coefficient of Variation 24.2 |
| Pt 2: MK-3281 800 mg BID (Panel E) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | 3.62 μM | Geometric Coefficient of Variation 25.7 |
| Pt 2: MK-3281 800 mg BID (Panel E) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.76 μM | Geometric Coefficient of Variation 29.7 |
| Pt 2: MK-3281 800 mg BID (Panel E) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | NA μM | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.64 μM | Geometric Coefficient of Variation 66.1 |
| Pt 2: MK-3281 800 mg BID (Panel F) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | NA μM | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | 3.09 μM | Geometric Coefficient of Variation 26.9 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 10 | NA μM | — |
| Pt 2: MK-3281 1200 mg BID (Panel G) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 7 | 4.90 μM | Geometric Coefficient of Variation 32.1 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | 12-Hour Concentration of MK-3281 in Plasma (C12hr) | Day 1 | 0.64 μM | Geometric Coefficient of Variation 26.6 |
Secondary
Apparent Half-Life (t ½) of MK-3281
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 100 mg BID (Panel A) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | 17.2 hour | Standard Deviation 2.3 |
| Pt 1: MK-3281 200 mg BID (Panel B) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | 17.5 hour | Standard Deviation 2.9 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 400 mg BID (Panel C) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | 17.4 hour | Standard Deviation 2.5 |
| Pt 1: MK-3281 800 mg BID (Panel D) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | 16.9 hour | Standard Deviation 1.3 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | 18.3 hour | Standard Deviation 4 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | NA hour | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | 19.7 hour | Standard Deviation 3.3 |
| Pt 2: MK-3281 800 mg BID (Panel F) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | NA hour | — |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Apparent Half-Life (t ½) of MK-3281 | Day 7 | 19.5 hour | Standard Deviation 2 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Apparent Half-Life (t ½) of MK-3281 | Day 10 | NA hour | — |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | 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 |
| Pt 1: MK-3281 100 mg BID (Panel A) | 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 | — |
| Pt 1: MK-3281 100 mg BID (Panel A) | 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 |
| Pt 1: MK-3281 200 mg BID (Panel B) | 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 | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 1 | 12.39 μM·hr | Geometric Coefficient of Variation 36.2 |
| Pt 1: MK-3281 200 mg BID (Panel B) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 10 | 29.71 μM·hr | Geometric Coefficient of Variation 32.1 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 10 | 37.21 μM·hr | Geometric Coefficient of Variation 22.6 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 1 | 13.21 μM·hr | Geometric Coefficient of Variation 45 |
| Pt 1: MK-3281 400 mg BID (Panel C) | 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 | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | 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 | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 1 | 18.12 μM·hr | Geometric Coefficient of Variation 70.9 |
| Pt 1: MK-3281 800 mg BID (Panel D) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 10 | 67.11 μM·hr | Geometric Coefficient of Variation 28.1 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 7 | 61.08 μM·hr | Geometric Coefficient of Variation 20.1 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 1 | 12.78 μM·hr | Geometric Coefficient of Variation 22.4 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 10 | NA μM·hr | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 1 | 11.36 μM·hr | Geometric Coefficient of Variation 47.7 |
| Pt 2: MK-3281 800 mg BID (Panel F) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 10 | NA μM·hr | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 7 | 51.68 μM·hr | Geometric Coefficient of Variation 29.8 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 10 | NA μM·hr | — |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 7 | 88.21 μM·hr | Geometric Coefficient of Variation 37 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Time 12 Hours (AUC[0-12]) of MK-3281 | Day 1 | 12.01 μM·hr | Geometric Coefficient of Variation 27.5 |
Secondary
AUC (0-12hr) Accumulation Ratio of MK-3281
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).
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 2.3 ratio | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 2.4 ratio | — |
| Pt 1: MK-3281 400 mg BID (Panel C) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 2.8 ratio | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 3.7 ratio | — |
| Pt 2: MK-3281 800 mg BID (Panel E) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 4.8 ratio | 90% Confidence Interval 4 |
| Pt 2: MK-3281 800 mg BID (Panel F) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 4.5 ratio | 90% Confidence Interval 3.3 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | AUC (0-12hr) Accumulation Ratio of MK-3281 | 7.3 ratio | 90% Confidence Interval 2 |
Secondary
C12hr Accumulation Ratio of MK-3281
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | C12hr Accumulation Ratio of MK-3281 | 2.5 ratio | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | C12hr Accumulation Ratio of MK-3281 | 2.7 ratio | — |
| Pt 1: MK-3281 400 mg BID (Panel C) | C12hr Accumulation Ratio of MK-3281 | 2.6 ratio | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | C12hr Accumulation Ratio of MK-3281 | 3.0 ratio | — |
| Pt 2: MK-3281 800 mg BID (Panel E) | C12hr Accumulation Ratio of MK-3281 | 4.7 ratio | 90% Confidence Interval 4 |
| Pt 2: MK-3281 800 mg BID (Panel F) | C12hr Accumulation Ratio of MK-3281 | 4.8 ratio | 90% Confidence Interval 3.3 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | C12hr Accumulation Ratio of MK-3281 | 7.7 ratio | 90% Confidence Interval 2 |
Secondary
Cmax Accumulation Ratio of MK-3281
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | Cmax Accumulation Ratio of MK-3281 | 1.7 ratio | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | Cmax Accumulation Ratio of MK-3281 | 2.0 ratio | — |
| Pt 1: MK-3281 400 mg BID (Panel C) | Cmax Accumulation Ratio of MK-3281 | 2.8 ratio | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Cmax Accumulation Ratio of MK-3281 | 2.9 ratio | — |
| Pt 2: MK-3281 800 mg BID (Panel E) | Cmax Accumulation Ratio of MK-3281 | 4.2 ratio | 90% Confidence Interval 4 |
| Pt 2: MK-3281 800 mg BID (Panel F) | Cmax Accumulation Ratio of MK-3281 | 3.5 ratio | 90% Confidence Interval 3.3 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Cmax Accumulation Ratio of MK-3281 | 6.4 ratio | 90% Confidence Interval 2 |
Secondary
Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pt 2: MK-3281 800 mg BID (Panel E) | Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days | 1.95 log(IU/ml) |
| Pt 2: MK-3281 800 mg BID (Panel F) | Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days | 1.34 log(IU/ml) |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Maximum HCV Viral Load Change From Baseline Over Study Following MK-3281 Dosing For 7 Days | 0.37 log(IU/ml) |
Secondary
Maximum Plasma Concentration (Cmax) of MK-3281
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | 1.28 μM | Geometric Coefficient of Variation 28.3 |
| Pt 1: MK-3281 100 mg BID (Panel A) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | NA μM | — |
| Pt 1: MK-3281 100 mg BID (Panel A) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 0.74 μM | Geometric Coefficient of Variation 32.6 |
| Pt 1: MK-3281 200 mg BID (Panel B) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | NA μM | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 1.75 μM | Geometric Coefficient of Variation 39.1 |
| Pt 1: MK-3281 200 mg BID (Panel B) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | 3.45 μM | Geometric Coefficient of Variation 36.2 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | 4.97 μM | Geometric Coefficient of Variation 44.1 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 1.80 μM | Geometric Coefficient of Variation 48.3 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | NA μM | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | NA μM | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 2.73 μM | Geometric Coefficient of Variation 75.9 |
| Pt 1: MK-3281 800 mg BID (Panel D) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | 7.83 μM | Geometric Coefficient of Variation 48.8 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | 6.78 μM | Geometric Coefficient of Variation 23.9 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 1.61 μM | Geometric Coefficient of Variation 24.9 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | NA μM | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 1.60 μM | Geometric Coefficient of Variation 43.7 |
| Pt 2: MK-3281 800 mg BID (Panel F) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | NA μM | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | 5.60 μM | Geometric Coefficient of Variation 33.3 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 10 | NA μM | — |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 7 | 10.73 μM | Geometric Coefficient of Variation 40.5 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Maximum Plasma Concentration (Cmax) of MK-3281 | Day 1 | 1.69 μM | Geometric Coefficient of Variation 28.4 |
Secondary
Time To Reach Cmax (Tmax) of MK-3281
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pt 1: MK-3281 100 mg BID (Panel A) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | 3.5 hour | Full Range 40.3 |
| Pt 1: MK-3281 100 mg BID (Panel A) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 100 mg BID (Panel A) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 3.0 hour | Full Range 42.3 |
| Pt 1: MK-3281 200 mg BID (Panel B) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 200 mg BID (Panel B) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 2.0 hour | Full Range 35.2 |
| Pt 1: MK-3281 200 mg BID (Panel B) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | 3.0 hour | Full Range 32.1 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | 3.5 hour | Full Range 26.3 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 5.0 hour | Full Range 40.5 |
| Pt 1: MK-3281 400 mg BID (Panel C) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | NA hour | — |
| Pt 1: MK-3281 800 mg BID (Panel D) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 3.0 hour | Full Range 73.1 |
| Pt 1: MK-3281 800 mg BID (Panel D) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | 3.0 hour | Full Range 24.2 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | 2.3 hour | Full Range 25.7 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 2.5 hour | Full Range 29.7 |
| Pt 2: MK-3281 800 mg BID (Panel E) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | NA hour | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 3.0 hour | Full Range 66.1 |
| Pt 2: MK-3281 800 mg BID (Panel F) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | NA hour | — |
| Pt 2: MK-3281 800 mg BID (Panel F) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | 2.0 hour | Full Range 26.9 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Time To Reach Cmax (Tmax) of MK-3281 | Day 10 | NA hour | — |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Time To Reach Cmax (Tmax) of MK-3281 | Day 7 | 1.0 hour | Full Range 32.1 |
| Pt 2: MK-3281 1200 mg BID (Panel G) | Time To Reach Cmax (Tmax) of MK-3281 | Day 1 | 3.0 hour | Full Range 26.6 |