Study of Safety and Pharmacokinetics of MK-8242 in Partic... | NCT01463696

ID	Type	Description	Link
2011-001346-15	EudraCT Number
MK-8242-006	Other Identifier	Merck Protocol Number

Study of Safety and Pharmacokinetics of MK-8242 in Partic... | NCT01463696 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MK-8242 60 mg BID	Experimental	In Cycle 1, participants received MK-8242 60 mg administered orally (PO) twice a day (BID) on Days 1-6 and PO once daily (QD) in the morning on Day 7 of the 21-day cycle to accommodate pharmacokinetic (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.	Drug: MK-8242
MK-8242 120 mg BID	Experimental	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.	Drug: MK-8242
MK-8242 170 mg BID	Experimental	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.	Drug: MK-8242
MK-8242 250 mg BID	Experimental	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.	Drug: MK-8242

Name	Type	Description	Arm Group Labels	Other Names
MK-8242	Drug	10 mg, 100 mg and 150 mg capsules	MK-8242 120 mg BID MK-8242 170 mg BID MK-8242 250 mg BID MK-8242 300 mg BID

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Cycle 1 (21 days)

Secondary Outcomes

Measure	Description	Time Frame
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.	Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28240971	Result	Wagner AJ, Banerji U, Mahipal A, Somaiah N, Hirsch H, Fancourt C, Johnson-Levonas AO, Lam R, Meister AK, Russo G, Knox CD, Rose S, Hong DS. Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors. J Clin Oncol. 2017 Apr 20;35(12):1304-1311. doi: 10.1200/JCO.2016.70.7117. Epub 2017 Feb 27.

Arm/Group Information

ID	Title	Description
FG000	MK-8242 60 mg BID	In Cycle 1, participants received MK-8242 60 mg administered orally (PO) twice a day (BID) on Days 1-6 and PO once daily (QD) in the morning on Day 7 of the 21-day cycle to accommodate pharmacokinetic (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.
FG001	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.
FG002	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.
FG003	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.
FG004	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.
FG005	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.
FG006	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.
FG007	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0001 subjects FG0016 subjects FG0023 subjects FG0037 subjects FG0043 subjects FG0056 subjects FG00616 subjects FG0076 subjects
Treated		FG0001 subjects FG0016 subjects FG0023 subjects FG0037 subjects FG004
COMPLETED		FG0001 subjects FG0014 subjects FG0022 subjects FG0033 subjects FG004
NOT COMPLETED		FG0000 subjects FG0012 subjects FG0021 subjects FG0034 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0011 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
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.	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.	Posted		Number		Participants		Cycle 1 (21 days)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp.	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

Title

Denominators

Categories

Title	Measurements
	BG00047.0± NAOnly 1 participant in population; no SD calculated. BG00160.0± 11.0 BG00268.3± 7.4 BG00360.3± 11.4 BG00453.3± 12.3 BG00558.2± 10.2 BG00663.9± 10.4 BG00762.5± 12.8 BG00861.3± 10.8

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.
OG007	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.

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.

The All Participants as Treated (APaT) population consisted of all participants who received at least one dose of study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

Cycle 1, Day 1 pre-dose and through 24 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.
OG007	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.

Units	Counts
Participants	OG0001 OG0015 OG0023 OG003

Title

Denominators

Categories

Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6)

Title	Measurements
	OG000162± NAOnly 1 participant had PK parameter assessed; no geometric coefficient of variation was calculated. OG001402± 101.2 OG002813

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.

The APaT population consisted of all participants who received at least one dose of study drug.

Posted

Median

Full Range

Hours

Cycle 1, Day 1 pre-dose and through 12 hours postdose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.
OG007	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.

Units	Counts
Participants	OG0001 OG0015 OG0023 OG003

Title

Denominators

Categories

Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6)

Title	Measurements
	OG0002.03(NA to NA)Only 1 participant had PK parameter assessed; no full range was calculated. OG0012.07(1.95 to 6.08) OG0024.30

Secondary

Area Under the Concentration Time Curve From Hour 0 to Hour 12 (AUC0-12) for MK-8242

The APaT population consisted of all participants who received at least one dose of study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

hr*nM

Cycle 1, Day 1 and Day 7, Hour 0 through Hour 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.
OG007	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.

Units	Counts
Participants	OG0001 OG0015 OG0023 OG003

Title

Denominators

Categories

Day 1 (n=1, 4, 1, 3, 3, 2, 12, 4)

Title	Measurements
	OG000548± NAOnly 1 participant had PK parameter assessed; no geometric coefficient of variation was calculated. OG0011820± 51.2 OG00211000

Secondary

AUC at Time of Last Sample (AUClast) for MK-8242

The APaT population consisted of all participants who received at least one dose of study drug.

Posted

Geometric Mean

Geometric Coefficient of Variation

hr*nM

Cycle 1, Day 1 pre-dose and through 12 hours post dose; Cycle 1 Day 7 pre-dose and through 48 hours post dose

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.
OG007	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.

Units	Counts
Participants	OG0001 OG0015 OG0023 OG003

Title

Denominators

Categories

Day 1 (n=1, 5, 3, 6, 3, 6, 14, 6)

Title	Measurements
	OG000509± NAOnly 1 participant had PK parameter assessed; no geometric coefficient of variation was calculated. OG0011380± 72.0 OG0023240

Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3)

Title	Measurements
	OG000150± NAOnly 1 participant had PK parameter assessed; no geometric coefficient of variation was calculated. OG001551± 90.1 OG0021680± 30.2 OG0031030± 133.7 OG0041720± 89.7 OG0051930± 52.4 OG0063070± 38.7 OG0071800± 63.0

Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3)

Title	Measurements
	OG0001.98(NA to NA)Only 1 participant had PK parameter assessed; no full range was calculated. OG0014.00(1.88 to 6.08) OG0022.00(2.00 to 4.00) OG0033.23(2.00 to 11.97) OG0042.00(2.00 to 2.00) OG0054.00(2.00 to 5.97) OG0063.03(2.00 to 6.92) OG0072.08(2.00 to 4.00)

Day 7 (n=1, 5, 3, 6, 3, 4, 12, 3)

Title	Measurements
	OG000706± NAOnly 1 participant had PK parameter assessed; no geometric coefficient of variation was calculated. OG0012450± 57.9 OG0027190± 24.7 OG0036710± 130.9 OG0048720± 65.1 OG00513100± 70.2 OG00616500± 41.2 OG00713400± 77.8

Day 7 (n=1, 5, 3, 6, 3, 5, 12, 3)

Title	Measurements
	OG000677± NAOnly 1 participant had PK parameter assessed; no geometric coefficient of variation was calculated. OG0012260± 65.0 OG0028290± 25.1 OG0037590± 103 OG00411300± 75.0 OG00515100± 81.1 OG00621400± 48.2 OG00717300± 90.4