Solid Tumors
Conditions
Brief summary
This study is being done to evaluate the safety and pharmacokinetic profile of MK-8242 and its active metabolite (M16) in participants with advanced solid tumors. In Part 1 of the study, the study drug dose will be escalated to determine the maximum tolerated dose (MTD). In Part 2 of the study, the MTD will be confirmed and the recommended Phase 2 dose (RPTD) established; the effect of MK-8242 on liposarcoma and other tumor types will also be evaluated.
Detailed description
Participants are considered to have completed the study after Cycle 12. Amendment 4 (14 April 2015) was done to allow participants on active treatment at the time the study was closed to enrollment to continue study treatment beyond Cycle 12 if deriving clinical benefit, at the Investigator's discretion.
Interventions
DRUGMK-8242
10 mg, 100 mg and 150 mg capsules
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed advanced solid tumor for which there are no effective standard therapy options * Willing to provide tumor tissue for p53 wild type gene analysis * Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 * Adequate organ function * Female participants and male participants and their partners who are of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of study drug * At least one measurable lesion * In Part 2, participants with liposarcoma must have a confirmed well-differentiated or de-differentiated histology
Exclusion criteria
* Known treated or untreated leptomeningeal metastases, or metastatic central nervous system disease * History of recent myocardial infarction (within the past year); or with unstable or uncontrolled angina, New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality * Uncontrolled active infection on optimal systemic treatment * Clinically significant hepatitis or hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive * Persistent, unresolved common terminology criteria for adverse events (CTCAE v4.0) ≥Grade 2 drug-related toxicity associated with previous treatment except for alopecia * Radiation therapy or other loco-regional therapy within 2 weeks prior to study * Use of moderate and strong cytochrome P450 inhibitors or inducers within 1 week prior to study * Chemotherapy or any investigational drug(s) within 4 weeks prior to study * Known hypersensitivity to MK-8242 or its components * Nursing, pregnant, or intention to become pregnant during the study * Initiating bisphosphonate therapy or adjusting the bisphosphonate dose or regimen within 30 days of Cycle 1 Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (21 days) | DLT was defined as: any drug-related hematologic toxicity ≥ Grade 3 lasting ≥1 week, ≥ Grade 3 thrombocytopenia with bleeding, ≥ Grade 3 neutropenia with infection OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions/clarifications: 1) Grade 3 nausea, vomiting, diarrhea, and dehydration were excluded from the determination of DLT if, in the opinion of the investigator and sponsor, they occurred in a setting of inadequate treatment, 2) Grade 3 nausea, vomiting, diarrhea, and dehydration were each considered a DLT if they persisted despite 72 hours of maximal supportive care measures or 3) Any abnormal non-hematological laboratory value ≥ Grade 3 (that is not attributable to any other causes) was considered a DLT only if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for ≥1 week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose | PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8,and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7. |
| Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose | PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7. |
| Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12 | PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7. |
| AUC at Time of Last Sample (AUClast) for MK-8242 | Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose | PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-8242 60 mg BID In Cycle 1, participants received MK-8242 60 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 60 mg PO BID on Days 1-7 of each 21-day cycle. | 1 |
| MK-8242 120 mg BID In Cycle 1, participants received MK-8242 120 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 120 mg PO BID on Days 1-7 of each 21-day cycle. | 6 |
| MK-8242 170 mg BID In Cycle 1, participants received MK-8242 170 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 170 mg PO BID on Days 1-7 of each 21-day cycle. | 3 |
| MK-8242 250 mg BID In Cycle 1, participants received MK-8242 250 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 250 mg PO BID on Days 1-7 of each 21-day cycle. | 7 |
| MK-8242 300 mg BID In Cycle 1, participants received MK-8242 300 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 300 mg PO BID on Days 1-7 of each 21-day cycle. | 3 |
| MK-8242 350 mg BID In Cycle 1, participants received MK-8242 350 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 350 mg PO BID on Days 1-7 of each 21-day cycle. | 6 |
| MK-8242 400 mg BID In Cycle 1, participants received MK-8242 400 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 400 mg PO BID on Days 1-7 of each 21-day cycle. | 16 |
| MK-8242 500 mg BID In Cycle 1, participants received MK-8242 500 mg administered PO BID on Days 1-6 and PO QD in the morning on Day 7 of the 21-day cycle to accommodate PK sampling. In Cycle 2 and subsequent cycles, participants received MK-8242 500 mg PO BID on Days 1-7 of each 21-day cycle. | 6 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 2 | 0 | 1 | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Not Treated | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 0 | 1 | 0 | 1 | 0 | 1 | 4 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | MK-8242 60 mg BID | MK-8242 120 mg BID | MK-8242 170 mg BID | MK-8242 250 mg BID | MK-8242 300 mg BID | MK-8242 350 mg BID | MK-8242 400 mg BID | MK-8242 500 mg BID | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.0 Years | 60.0 Years STANDARD_DEVIATION 11 | 68.3 Years STANDARD_DEVIATION 7.4 | 60.3 Years STANDARD_DEVIATION 11.4 | 53.3 Years STANDARD_DEVIATION 12.3 | 58.2 Years STANDARD_DEVIATION 10.2 | 63.9 Years STANDARD_DEVIATION 10.4 | 62.5 Years STANDARD_DEVIATION 12.8 | 61.3 Years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 6 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 1 Participants | 4 Participants | 2 Participants | 4 Participants | 10 Participants | 3 Participants | 29 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 | 1 / 1 | 6 / 6 | 3 / 3 | 7 / 7 | 3 / 3 | 6 / 6 | 15 / 15 | 6 / 6 |
| serious Total, serious adverse events | 0 / 1 | 1 / 6 | 0 / 3 | 2 / 7 | 1 / 3 | 3 / 6 | 5 / 15 | 4 / 6 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as: any drug-related hematologic toxicity ≥ Grade 3 lasting ≥1 week, ≥ Grade 3 thrombocytopenia with bleeding, ≥ Grade 3 neutropenia with infection OR non-hematologic DLTs that were any Grade 3, 4, or 5 toxicity with the following exceptions/clarifications: 1) Grade 3 nausea, vomiting, diarrhea, and dehydration were excluded from the determination of DLT if, in the opinion of the investigator and sponsor, they occurred in a setting of inadequate treatment, 2) Grade 3 nausea, vomiting, diarrhea, and dehydration were each considered a DLT if they persisted despite 72 hours of maximal supportive care measures or 3) Any abnormal non-hematological laboratory value ≥ Grade 3 (that is not attributable to any other causes) was considered a DLT only if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for ≥1 week.
Time frame: Cycle 1 (21 days)
Population: The DLT-evaluable population consisted of participants who received at least one dose of MK-8242 and completed Cycle 1 of Part 1 (dose escalation) or the dose confirmation portion of Part 2, or discontinued due to toxicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8242 60 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| MK-8242 120 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| MK-8242 170 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| MK-8242 250 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| MK-8242 300 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| MK-8242 350 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| MK-8242 400 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| MK-8242 500 mg BID | Number of Participants With Dose Limiting Toxicities (DLTs) | 4 Participants |
Secondary
Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242
PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
Time frame: Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12
Population: The APaT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8242 60 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 548 hr*nM | — |
| MK-8242 60 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 706 hr*nM | — |
| MK-8242 120 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 1820 hr*nM | Geometric Coefficient of Variation 51.2 |
| MK-8242 120 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 2450 hr*nM | Geometric Coefficient of Variation 57.9 |
| MK-8242 170 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 11000 hr*nM | — |
| MK-8242 170 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 7190 hr*nM | Geometric Coefficient of Variation 24.7 |
| MK-8242 250 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 6710 hr*nM | Geometric Coefficient of Variation 130.9 |
| MK-8242 250 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 5550 hr*nM | Geometric Coefficient of Variation 100.1 |
| MK-8242 300 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 8720 hr*nM | Geometric Coefficient of Variation 65.1 |
| MK-8242 300 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 5020 hr*nM | Geometric Coefficient of Variation 45.4 |
| MK-8242 350 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 13100 hr*nM | Geometric Coefficient of Variation 70.2 |
| MK-8242 350 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 6940 hr*nM | Geometric Coefficient of Variation 110.7 |
| MK-8242 400 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 16500 hr*nM | Geometric Coefficient of Variation 41.2 |
| MK-8242 400 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 16800 hr*nM | Geometric Coefficient of Variation 45.3 |
| MK-8242 500 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3) | 13400 hr*nM | Geometric Coefficient of Variation 77.8 |
| MK-8242 500 mg BID | Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242 | Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4) | 24100 hr*nM | Geometric Coefficient of Variation 46 |
Secondary
AUC at Time of Last Sample (AUClast) for MK-8242
PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
Time frame: Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
Population: The APaT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8242 60 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 509 hr*nM | — |
| MK-8242 60 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 677 hr*nM | — |
| MK-8242 120 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 1380 hr*nM | Geometric Coefficient of Variation 72 |
| MK-8242 120 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 2260 hr*nM | Geometric Coefficient of Variation 65 |
| MK-8242 170 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 3240 hr*nM | Geometric Coefficient of Variation 131 |
| MK-8242 170 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 8290 hr*nM | Geometric Coefficient of Variation 25.1 |
| MK-8242 250 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 5410 hr*nM | Geometric Coefficient of Variation 69 |
| MK-8242 250 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 7590 hr*nM | Geometric Coefficient of Variation 103 |
| MK-8242 300 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 4830 hr*nM | Geometric Coefficient of Variation 49.7 |
| MK-8242 300 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 11300 hr*nM | Geometric Coefficient of Variation 75 |
| MK-8242 350 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 6350 hr*nM | Geometric Coefficient of Variation 152 |
| MK-8242 350 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 15100 hr*nM | Geometric Coefficient of Variation 81.1 |
| MK-8242 400 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 21400 hr*nM | Geometric Coefficient of Variation 48.2 |
| MK-8242 400 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 16700 hr*nM | Geometric Coefficient of Variation 41.9 |
| MK-8242 500 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 17400 hr*nM | Geometric Coefficient of Variation 84.7 |
| MK-8242 500 mg BID | AUC at Time of Last Sample (AUClast) for MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 17300 hr*nM | Geometric Coefficient of Variation 90.4 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of MK-8242
PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8,and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
Time frame: Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
Population: The All Participants as Treated (APaT) population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-8242 60 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 162 nM | — |
| MK-8242 60 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 150 nM | — |
| MK-8242 120 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 402 nM | Geometric Coefficient of Variation 101.2 |
| MK-8242 120 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 551 nM | Geometric Coefficient of Variation 90.1 |
| MK-8242 170 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 813 nM | Geometric Coefficient of Variation 208.7 |
| MK-8242 170 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 1680 nM | Geometric Coefficient of Variation 30.2 |
| MK-8242 250 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 1030 nM | Geometric Coefficient of Variation 133.7 |
| MK-8242 250 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 1210 nM | Geometric Coefficient of Variation 80.4 |
| MK-8242 300 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 1720 nM | Geometric Coefficient of Variation 89.7 |
| MK-8242 300 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 1320 nM | Geometric Coefficient of Variation 33.4 |
| MK-8242 350 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 1510 nM | Geometric Coefficient of Variation 166.2 |
| MK-8242 350 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 1930 nM | Geometric Coefficient of Variation 52.4 |
| MK-8242 400 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 3820 nM | Geometric Coefficient of Variation 39.4 |
| MK-8242 400 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 3070 nM | Geometric Coefficient of Variation 38.7 |
| MK-8242 500 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 4240 nM | Geometric Coefficient of Variation 45.5 |
| MK-8242 500 mg BID | Maximum Observed Plasma Concentration (Cmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 1800 nM | Geometric Coefficient of Variation 63 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of MK-8242
PK plasma samples were to be collected at the following time points: 0, 0.5, 1, 2, 4, 6, 8 and 12 hours after the first dose on Day 1; and 0, 0.5, 1, 2, 4, 6, 8, 12, 24 (Day 8) and 48 (Day 9) hours post-dose on Day 7.
Time frame: Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose
Population: The APaT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-8242 60 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 1.98 Hours |
| MK-8242 60 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 2.03 Hours |
| MK-8242 120 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 2.07 Hours |
| MK-8242 120 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 4.00 Hours |
| MK-8242 170 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 2.00 Hours |
| MK-8242 170 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 4.30 Hours |
| MK-8242 250 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 4.00 Hours |
| MK-8242 250 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 3.23 Hours |
| MK-8242 300 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 2.18 Hours |
| MK-8242 300 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 2.00 Hours |
| MK-8242 350 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 4.04 Hours |
| MK-8242 350 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 4.00 Hours |
| MK-8242 400 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 2.00 Hours |
| MK-8242 400 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 3.03 Hours |
| MK-8242 500 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6) | 3.04 Hours |
| MK-8242 500 mg BID | Time to Maximum Plasma Concentration (Tmax) of MK-8242 | Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3) | 2.08 Hours |