Safety, Tolerability and Pharmacokinetics Study of MK-725... | NCT03326986 | Trialant
NCT03326986
Sponsor
Merck Sharp & Dohme LLC
Status
Completed
Last Update Posted
Jan 9, 2020Actual
Enrollment
24Actual
Phase
Phase 1
Conditions
Pharmacokinetics
Cancer
Interventions
MK-7252
Placebo
Countries
Belgium
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Derived Section
Miscellaneous Info Module
Version Holder
NCT03326986
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
7252-001
Secondary IDs
ID
Type
Description
Link
2017-003407-22
EudraCT Number
MK-7252-001
Other Identifier
Merck
Brief Title
Safety, Tolerability and Pharmacokinetics Study of MK-7252 in Healthy Adult Participants (MK-7252-001)
Official Title
A Single Ascending Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-7252 in Healthy Subjects
Acronym
Not provided
Organization
Merck Sharp & Dohme LLCINDUSTRY
Status Module
Record Verification Date
Dec 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 10, 2017Actual
Primary Completion Date
Dec 17, 2018Actual
Completion Date
Dec 17, 2018Actual
First Submitted Date
Oct 27, 2017
First Submission Date that Met QC Criteria
Oct 27, 2017
First Posted Date
Oct 31, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Nov 21, 2019
Results First Submitted that Met QC Criteria
Dec 19, 2019
Results First Posted Date
Jan 9, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Dec 19, 2019
Last Update Posted Date
Jan 9, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Merck Sharp & Dohme LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of MK-7252 in healthy adults. Participants receive ascending doses of MK-7252 over five treatment periods. Each treatment period is separated by a 7-day washout period.
Upon review of the interim safety and preliminary PK data of human exposure to date, Protocol Amendment 3 includes a third panel of participants, Panel C, to assess the PK of higher doses of MK-7252 and to assess the food effect of MK-7252.
Detailed Description
Three panels (Panels A, B, and C) of 8 healthy participants (n=6 MK-7252, n=2 placebo) are enrolled. In Panels A and B, participants will alternately receive single rising doses of MK-7252 or placebo for 5 treatment periods. In Panel C, participants will receive single rising doses of MK-7252 or placebo for up to 5 treatment periods. All doses in Panels A and B will be administered in the fasted state during the 5 treatment periods. Doses in Panel C will be administered in a fasted state in treatment periods 1 through 4 and the treatment period 1 dose will be repeated in a fed state during treatment period 5. Panel A will begin first. At least 3 days will elapse before participants in Panel B will receive the next higher dose. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods. All participants in the treatment periods of all panels (with exception of 120 mg fasted/fed periods in Panel C) will be randomly assigned to either study drug or placebo; that is a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants in Panel C will receive 120 mg MK-7252 in a fasted and fed state. In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥2 hours, dose escalation in that participant will be halted and the participant may be withdrawn from the study or re-challenged at same dose or at a lower or divided dose. Participants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
During the study, participants in Panel A were planned to receive placebo, 1 mg, 6 mg, 24 mg, 72 mg and 108 mg, all in a fasted state in 5 periods. Participants in Panel B were planned to receive placebo, 3 mg, 12 mg, 48 mg, 72 mg and 162 mg, all in a fasted state in 5 periods. All periods in Panels A and B were conducted. Participants in Panel C were planned to receive placebo fasted, placebo fed, 120 mg fasted, 240 mg fasted, 360 mg fasted, 540 mg fasted, and 120 mg fed in 5 periods. Periods 4 and 5 were not conducted and, as a result, the 240 mg fasted, 360 mg fasted, 540 mg fasted, 120 mg fed, and placebo fed doses were not administered. A 180 mg fasted dose was added during Period 3.
Conditions Module
Conditions
Pharmacokinetics
Cancer
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
24Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Panel A
Experimental
Participants receive either a single dose of MK-7252 or Placebo in a fasted state in each of five alternating treatment dosing periods as indicated. The planned dose levels include: Placebo for MK-7252, 1 mg of MK-7252, 6 mg of MK-7252, 24 mg of MK-7252, 72 mg of MK-7252, and 108 mg of MK-7252. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods
Drug: MK-7252
Drug: Placebo
Panel B
Experimental
Participants receive either a single dose of MK-7252 or Placebo in a fasted state in each of five alternating treatment dosing periods as indicated. The planned dose levels include: Placebo for MK-7252, 3 mg of MK-7252, 12 mg of MK-7252, 48 mg of MK-7252, 72 mg of MK-7252, and 162 mg of MK-7252. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods
Drug: MK-7252
Drug: Placebo
Panel C
Experimental
Participants receive either a single dose of MK-7252 or Placebo in up to 5 treatment dosing periods as indicated: Placebo for MK-7252, 120 mg of MK-7252 in a fasted state, 240 mg of MK-7252, 360 mg of MK-7252, 540 mg of MK-7252, and 120 mg of MK-7252 in a fed state. There is a minimum of a 7-day washout period between each treatment period or dose administration. The planned dose levels may be adjusted downward or replaced based on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed after previous treatment periods
Interventions
Name
Type
Description
Arm Group Labels
Other Names
MK-7252
Drug
1 mg/mL or 20 mg/mL of powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL
Panel A
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Adverse events are reported by dose taken at time of event and not by panel or period. The adverse events for placebo are pooled over periods across panels. The number of participants who experienced at least one AE is presented.
Up to approximately 21 weeks
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Discontinuations are reported by dose taken at time of event. The discontinuations for placebo are pooled over periods across panels. The number of participants who discontinued study treatment due to an AE is presented.
Up to approximately 19 weeks
Secondary Outcomes
Measure
Description
Time Frame
MK-7252 Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-∞ reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. Pharmacokinetic (PK) results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-∞ following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-∞ in the fasted stated in Panel C, the fed state dose was not administered.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female participants of non-childbearing potential (Note: If postmenopausal female: participant is without menses for at least 1 year and has a documented follicle stimulating hormone [FSH] level in the postmenopausal range at pre-trial [screening] - OR - If surgically sterile female: participant is status post hysterectomy, oophorectomy or tubal ligation.)
Body Mass Index (BMI) between 18.5 and 32 kg/m^2, inclusive. BMI = weight (kg)/height (m)^2.
While in semi-recumbent position, has a systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mm Hg and a respiratory rate ≤20 breaths/min at the pre-study (screening) visit and prior to randomization.
Judged to be in good health based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG) performed prior to randomization.
Non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months.
Exclusion Criteria:
Mentally or legally incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder of the last 5 years.
History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases.
History of liver disease (chronic hepatitis, cirrhosis, etc.).
History of cancer (malignancy). Exceptions include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix and other malignancies which have been successfully treated ≥10 years prior to the pre-study (screening) visit.
History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
Tests positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study (screening) visit.
Participated in another investigational study within 4 weeks (or 5 half-lives), whichever is greater, prior to the pre-study (screening) visit.
Taken a Proton Pump Inhibitor (PPI) during the 5 days prior to start of study treatment.
Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the post-study visit.
Consumes >3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day.
Consumes excessive amounts, defined as >6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
Regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year. Participants must have a negative result for urine drug screen test prior to randomization.
Participants in Panels A and B received a single-rising dose of MK-7252 or placebo in 5 alternating dosing periods. Participants in Panel C received a single-rising dose of MK-7252 or placebo in 3/5 planned periods (P). A 180 mg dose was added (P3). P4-5 were not run so the 240, 360, 540, and 120 mg fed and placebo fed doses were not given.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Panel A
Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-7252 (1 mg, 6 mg, 24 mg, 72 mg, or 108 mg) and 2 participants received placebo in a fasted state. Dosing periods alternated with Panel B.
FG001
Panel B
Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-7252 (3 mg, 12 mg, 48 mg, 72 mg, or 162 mg) and 2 participants received placebo in a fasted state. Dosing periods alternated with Panel A.
FG002
Panel C
Within each of 3 single dose treatment periods, 6 participants received a single dose of MK-7252 (120 mg or 180 mg) and 2 participants received placebo in a fasted state. The 120 mg dose of MK-7252 was administered in the first 2 periods and the 180 mg dose was administered in the third period.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
FG0008 subjects
FG0018 subjects
FG0028 subjects
COMPLETED
FG0008 subjects
FG0018 subjects
FG0028 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
Baseline Characteristics Module
Baseline Analysis Population Description
All randomized participants
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Panel A
Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-7252 (1 mg, 6 mg, 24 mg, 72 mg, or 108 mg) and 2 participants received placebo in a fasted state. Dosing periods alternated with Panel B.
BG001
Panel B
Denominators
Units
Counts
Participants
BG000
Baseline Measures
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 Who Experienced at Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Adverse events are reported by dose taken at time of event and not by panel or period. The adverse events for placebo are pooled over periods across panels. The number of participants who experienced at least one AE is presented.
All participants who received at least 1 dose of study treatment and experienced an AE during the study period
Posted
Count of Participants
Participants
Up to approximately 21 weeks
ID
Title
Description
OG000
MK-7252 1 mg
Adverse Events Module
Frequency Threshold
0
Time Frame
Up to approximately 21 weeks
Description
The safety population includes all participants who received at least 1 dose of study treatment. Adverse events are reported by dose taken at time of event and not by panel or period. Post-study adverse events were pooled across all arms in the study (MK-7252 and placebo).
All-Cause Mortality Comment
Not provided
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-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
Serious Adverse Events
Not provided
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Palpitations
Cardiac disorders
MedDRA 21.1
Systematic Assessment
More Info Module
Limitations and Caveats
Not provided
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
Point of Contact
Title
Organization
Phone
Extension
Email
Senior Vice President, Global Clinical Development
Placebo powder for oral suspension administered with a water volume that brings the total ingested volume to approximately 240 mL
Panel A
Panel B
Panel C
Predose (Day 1) and 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
MK-7252 Area Under the Concentration-Time Curve From Zero to 24 Hours Postdose (AUC0-24hr)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-24hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-24hr following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-24hr in the fasted stated in Panel C, the fed state dose was not administered.
MK-7252 Area Under the Concentration-Time Curve From Zero to 12 Hours Postdose (AUC0-12hr)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-12hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-12hr following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-12hr in the fasted stated in Panel C, the fed state dose was not administered.
MK-7252 Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUClast)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUClast reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUClast following a high-fat breakfast (fed state) was planned to be compared to the plasma AUClast in the fasted stated in Panel C, the fed state dose was not administered.
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 Cmax reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma Cmax following a high-fat breakfast (fed state) was planned to be compared to the plasma Cmax in the fasted stated in Panel C, the fed state dose was not administered.
MK-7252 Plasma Concentration at 12 Hours Postdose (C12hr)
Blood samples were obtained 12 hours postdose to calculate the plasma MK-7252 C12hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. For participants in a given dose that had C12hr values less than the lower limit of quantification (LLOQ), the C12hr value was imputed as half x LLOQ. The LLOQ was 2.74 nmol/L. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma C12hr following a high-fat breakfast (fed state) was planned to be compared to the plasma C12hr in the fasted stated in Panel C, the fed state dose was not administered.
12 hours postdose
MK-7252 Plasma Concentration at 24 Hours Postdose (C24hr)
Blood samples were obtained 24 hours postdose to calculate the plasma MK-7252 C24hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. For participants in a given dose that had C24hr values less than the lower limit of quantification (LLOQ), the C24hr value was imputed as half x LLOQ. The LLOQ was 2.74 nmol/L. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma C24hr following a high-fat breakfast (fed state) was planned to be compared to the plasma C24hr in the fasted stated in Panel C, the fed state dose was not administered.
24 hours postdose
MK-7252 Time to Reach Maximal Concentration (Tmax)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 Tmax. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma Tmax following a high-fat breakfast (fed state) was planned to be compared to the plasma Tmax in the fasted stated in Panel C, the fed state dose was not administered.
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 t½ reported as Geometric Mean with Percent Geometric Coefficient of Variation. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma t½ following a high-fat breakfast (fed state) was planned to be compared to the plasma t½ in the fasted stated in Panel C, the fed state dose was not administered.
Change From Baseline in Systolic Blood Pressure (SBP) at 4 Hours
Assessment of the change from baseline in SBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 SBP measurements: baseline and 4 hours postdose. SBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in SBP and a negative number indicates a decrease in SBP.
Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Systolic Blood Pressure (SBP) at 24 Hours
Assessment of the change from baseline in SBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 SBP measurements: baseline and 24 hours postdose. SBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in SBP and a negative number indicates a decrease in SBP.
Baseline (Predose Day 1) and 24 hours postdose
Change From Baseline in Diastolic Blood Pressure (DBP) at 4 Hours
Assessment of the change from baseline in DBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 DBP measurements: baseline and 4 hours postdose. DBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in DBP and a negative number indicates a decrease in DBP.
Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Diastolic Blood Pressure (DBP) at 24 Hours
Assessment of the change from baseline in DBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 DBP measurements: baseline and 24 hours postdose. DBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in DBP and a negative number indicates a decrease in DBP.
Baseline (Predose Day 1) and 24 hours postdose
Change From Baseline in Heart Rate (HR) at 4 Hours
Assessment of the change from baseline in HR was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 HR measurements: baseline and 4 hours postdose. HR results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in HR and a negative number indicates a decrease in HR.
Baseline (Predose Day 1) and 4 hours postdose
Change From Baseline in Heart Rate (HR) at 24 Hours
Assessment of the change from baseline in HR was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 HR measurements: baseline and 24 hours postdose. HR results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in HR and a negative number indicates a decrease in HR.
Baseline (Predose Day 1) and 24 hours postdose
Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-7252 (3 mg, 12 mg, 48 mg, 72 mg, or 162 mg) and 2 participants received placebo in a fasted state. Dosing periods alternated with Panel A.
BG002
Panel C
Within each of 3 single dose treatment periods, 6 participants received a single dose of MK-7252 (120 mg or 180 mg) and 2 participants received placebo in a fasted state. The 120 mg dose of MK-7252 was administered in the first 2 periods and the 180 mg dose was administered in the third period.
BG003
Total
Total of all reporting groups
8
BG0018
BG0028
BG00324
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00033.0± 10.2
BG00135.0± 9.5
BG00234.4± 9.3
BG00334.1± 9.3
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0012
BG0020
BG0033
Male
BG0007
BG0016
BG0028
BG00321
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG0020
BG0030
Not Hispanic or Latino
BG0008
BG0018
BG0028
BG00324
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG0020
BG0030
Asian
BG0000
BG0010
BG0020
BG0030
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
Black or African American
BG0000
BG0010
BG0020
BG0030
White
BG0008
BG0018
BG0028
BG00324
More than one race
BG0000
BG0010
BG0020
BG0030
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in a fasted state
OG007
MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG008
MK-7252 120 mg
Single oral dose of 120 mg MK-7252 administered in a fasted state
OG009
MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
MK-7252 180 mg
Single oral dose of 180 mg MK-7252 administered in a fasted state
OG011
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG0046
OG0056
OG00612
OG0076
OG0088
OG0096
OG0105
OG01122
Title
Denominators
Categories
Title
Measurements
OG0002
OG0015
OG0024
OG0035
OG0045
OG0054
OG0067
OG0075
OG0086
OG0094
OG0102
OG01115
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have had a causal relationship with this treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. Discontinuations are reported by dose taken at time of event. The discontinuations for placebo are pooled over periods across panels. The number of participants who discontinued study treatment due to an AE is presented.
All participants who received at least 1 dose of study treatment and discontinued during the study period
Posted
Count of Participants
Participants
Up to approximately 19 weeks
ID
Title
Description
OG000
MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in a fasted state
OG007
MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG008
MK-7252 120 mg
Single oral dose of 120 mg MK-7252 administered in a fasted state
OG009
MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
MK-7252 180 mg
Single oral dose of 180 mg MK-7252 administered in a fasted state
OG011
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
MK-7252 Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-∞ reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. Pharmacokinetic (PK) results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-∞ following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-∞ in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4-5 of Panel C were not conducted; the planned 120 mg fed dose (P 5) was not administered.
Posted
Geometric Least Squares Mean
95% Confidence Interval
hr•nmol/L
Predose (Day 1) and 0.25, 0.5, 1, 2, 4, 8, 10, 12, 24, 48, and 72 hours postdose
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Geometric mean and 95% confidence interval were not calculated for the 1 mg dose: there were insufficient data points above the lower limit of quantification of the assay (2.74 nM) to calculate the AUC0-∞ at this dose level.
OG001NA(NA to NA)Geometric mean and 95% confidence interval were not calculated for the 3 mg dose: there were insufficient data points above the lower limit of quantification of the assay (2.74 nM) to calculate the AUC0-∞ at this dose level.
OG002
Secondary
MK-7252 Area Under the Concentration-Time Curve From Zero to 24 Hours Postdose (AUC0-24hr)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-24hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-24hr following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-24hr in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00047.8(32.4 to 70.4)
OG001122(82.4 to 179)
OG002279(189 to 411)
OG003
Secondary
MK-7252 Area Under the Concentration-Time Curve From Zero to 12 Hours Postdose (AUC0-12hr)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUC0-12hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUC0-12hr following a high-fat breakfast (fed state) was planned to be compared to the plasma AUC0-12hr in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00047.8(32.5 to 70.4)
OG001121(82.5 to 179)
OG002278(189 to 409)
OG003
Secondary
MK-7252 Area Under the Concentration-Time Curve From Zero to Last Measurable Concentration (AUClast)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 AUClast reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma AUClast following a high-fat breakfast (fed state) was planned to be compared to the plasma AUClast in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00038.7(26.0 to 57.6)
OG001101(68.1 to 151)
OG002250(168 to 371)
OG003
Secondary
MK-7252 Maximal Plasma Concentration (Cmax)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 Cmax reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma Cmax following a high-fat breakfast (fed state) was planned to be compared to the plasma Cmax in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00021.2(15.4 to 29.4)
OG00151.7(37.4 to 71.5)
OG002117(84.6 to 162)
OG003
Secondary
MK-7252 Plasma Concentration at 12 Hours Postdose (C12hr)
Blood samples were obtained 12 hours postdose to calculate the plasma MK-7252 C12hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. For participants in a given dose that had C12hr values less than the lower limit of quantification (LLOQ), the C12hr value was imputed as half x LLOQ. The LLOQ was 2.74 nmol/L. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma C12hr following a high-fat breakfast (fed state) was planned to be compared to the plasma C12hr in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Posted
Geometric Least Squares Mean
90% Confidence Interval
nmol/L
12 hours postdose
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C12hr values for the 1 mg dose level being below the LLOQ (2.74 nmol/L).
OG001NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C12hr values for the 3 mg dose level being below the LLOQ (2.74 nmol/L).
OG002
Secondary
MK-7252 Plasma Concentration at 24 Hours Postdose (C24hr)
Blood samples were obtained 24 hours postdose to calculate the plasma MK-7252 C24hr reported as back-transformed least squares mean and confidence interval calculated using a linear mixed effects model performed on natural log-transformed values. For participants in a given dose that had C24hr values less than the lower limit of quantification (LLOQ), the C24hr value was imputed as half x LLOQ. The LLOQ was 2.74 nmol/L. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma C24hr following a high-fat breakfast (fed state) was planned to be compared to the plasma C24hr in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment, complied with the protocol to ensure data were likely to exhibit effects of treatment according to the scientific model, and had data available for endpoint. Periods 4-5 of Panel C was not conducted and planned 120 mg fed dose not administered. Analysis was not performed due to values being \
Posted
Geometric Least Squares Mean
90% Confidence Interval
nmol/L
24 hours postdose
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 1 mg dose level being below the LLOQ (2.74 nmol/L).
OG001NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 3 mg dose level being below the LLOQ (2.74 nmol/L).
OG002
Secondary
MK-7252 Time to Reach Maximal Concentration (Tmax)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 Tmax. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma Tmax following a high-fat breakfast (fed state) was planned to be compared to the plasma Tmax in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.00(0.50 to 1.00)
OG0010.75(0.50 to 1.00)
OG0020.75(0.50 to 1.00)
OG003
Secondary
MK-7252 Apparent Terminal Half-life (t½)
Blood samples were obtained predose (Day 1) and at designated times postdose to calculate the plasma MK-7252 t½ reported as Geometric Mean with Percent Geometric Coefficient of Variation. PK results were reported by dose taken in Panels A and B. For Panel C, PK results were reported by dose taken and by individual period. Periods in a panel were not conducted if it became evident that exposures at the escalated dosing would not adequately reach the projected PK target. Although the plasma t½ following a high-fat breakfast (fed state) was planned to be compared to the plasma t½ in the fasted stated in Panel C, the fed state dose was not administered.
All participants who received study treatment and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Periods (P) 4 and 5 of Panel C were not conducted; the planned 120 mg fed dose (P5) was not administered.
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0025
OG003
Title
Denominators
Categories
Title
Measurements
OG000NA± NAGeometric mean and 95% confidence interval were not calculated for the 1 mg dose: there were insufficient data points above the lower limit of quantification of the assay (2.74 nM) to calculate the t½ at this dose level.
OG001NA± NAGeometric mean and 95% confidence interval were not calculated for the 3 mg dose: there were insufficient data points above the lower limit of quantification of the assay (2.74 nM) to calculate the t½ at this dose level.
OG002
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) at 4 Hours
Assessment of the change from baseline in SBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 SBP measurements: baseline and 4 hours postdose. SBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in SBP and a negative number indicates a decrease in SBP.
All participants who received at least 1 dose of study treatment and had SBP assessments at baseline and 4 hours postdose
Posted
Mean
Standard Error
mmHg
Baseline (Predose Day 1) and 4 hours postdose
Measurement sets
Measurement sets
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
OG013
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0005.61± 1.94
OG0011.56± 2.57
OG0020.50± 2.66
OG003
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) at 24 Hours
Assessment of the change from baseline in SBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 SBP measurements: baseline and 24 hours postdose. SBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in SBP and a negative number indicates a decrease in SBP.
All participants who received at least 1 dose of study treatment and had SBP assessments at baseline and 24 hours postdose
Posted
Mean
Standard Error
mmHg
Baseline (Predose Day 1) and 24 hours postdose
Measurement sets
Measurement sets
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
OG013
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0002.83± 3.40
OG0010.89± 3.00
OG002-1.11± 1.56
OG003
Secondary
Change From Baseline in Diastolic Blood Pressure (DBP) at 4 Hours
Assessment of the change from baseline in DBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 DBP measurements: baseline and 4 hours postdose. DBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in DBP and a negative number indicates a decrease in DBP.
All participants who received at least 1 dose of study treatment and had DBP assessments at baseline and 4 hours postdose
Posted
Mean
Standard Error
mmHg
Baseline (Predose Day 1) and 4 hours postdose
Measurement sets
Measurement sets
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
OG013
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0001.11± 1.77
OG0011.61± 1.06
OG0020.33± 1.88
OG003
Secondary
Change From Baseline in Diastolic Blood Pressure (DBP) at 24 Hours
Assessment of the change from baseline in DBP was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 DBP measurements: baseline and 24 hours postdose. DBP results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in DBP and a negative number indicates a decrease in DBP.
All participants who received at least 1 dose of study treatment and had DBP assessments at baseline and 24 hours postdose
Posted
Mean
Standard Error
mmHg
Baseline (Predose Day 1) and 24 hours postdose
Measurement sets
Measurement sets
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
OG013
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.61± 1.31
OG0012.78± 3.13
OG002-2.67± 2.86
OG003
Secondary
Change From Baseline in Heart Rate (HR) at 4 Hours
Assessment of the change from baseline in HR was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 HR measurements: baseline and 4 hours postdose. HR results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in HR and a negative number indicates a decrease in HR.
All participants who received at least 1 dose of study treatment and had HR assessments at baseline and 4 hours postdose
Posted
Mean
Standard Error
beats per minute
Baseline (Predose Day 1) and 4 hours postdose
Measurement sets
Measurement sets
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
OG013
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG000-4.22± 1.82
OG001-0.28± 2.66
OG002-1.22± 1.68
OG003
Secondary
Change From Baseline in Heart Rate (HR) at 24 Hours
Assessment of the change from baseline in HR was obtained using a validated, semi-automated oscillometric device. Baseline was defined as the average of predose measurements. A measurement set was considered 2 HR measurements: baseline and 24 hours postdose. HR results are reported by dose taken. Placebo measurements are pooled over periods across panels. A positive number indicates an increase in HR and a negative number indicates a decrease in HR.
All participants who received at least 1 dose of study treatment and had HR assessments at baseline and 24 hours postdose
Posted
Mean
Standard Error
beats per minute
Baseline (Predose Day 1) and 24 hours postdose
Measurement sets
Measurement sets
ID
Title
Description
OG000
Panel A MK-7252 1 mg
Single oral dose of 1 mg MK-7252 administered in a fasted state
OG001
Panel B MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
OG002
Panel A MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
OG003
Panel B MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
OG004
Panel A MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
OG005
Panel B MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
OG006
Panel A MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered in Panel A in a fasted state
OG007
Panel B MK-7252 72 mg
Single oral dose of 72 mg MK-7252 administered Panel B in a fasted state
OG008
Panel A MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
OG009
Panel B MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
OG010
Panel C MK-7252 120 mg Period 1
Single oral dose of 120 mg MK-7252 administered in Panel C Period 1 in a fasted state
OG011
Panel C MK-7252 120 mg Period 2
Single oral dose of 120 mg MK-7252 administered in Panel C Period 2 in a fasted state
OG012
Panel C MK-7252 180 mg Period 3
Single oral dose of 180 mg MK-7252 administered in Panel C Period 3 in a fasted state
OG013
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
Units
Counts
Participants
OG0006
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG000-2.78± 2.01
OG0012.72± 2.03
OG0021.83± 1.38
OG003
0
6
0
6
2
6
EG001
MK-7252 3 mg
Single oral dose of 3 mg MK-7252 administered in a fasted state
0
6
0
6
5
6
EG002
MK-7252 6 mg
Single oral dose of 6 mg MK-7252 administered in a fasted state
0
6
0
6
4
6
EG003
MK-7252 12 mg
Single oral dose of 12 mg MK-7252 administered in a fasted state
0
6
0
6
5
6
EG004
MK-7252 24 mg
Single oral dose of 24 mg MK-7252 administered in a fasted state
0
6
0
6
5
6
EG005
MK-7252 48 mg
Single oral dose of 48 mg MK-7252 administered in a fasted state
0
6
0
6
4
6
EG006
MK-7252 72 mg
Single oral dose of 72 mg of MK-7252 administered in a fasted state
0
12
0
12
7
12
EG007
MK-7252 108 mg
Single oral dose of 108 mg MK-7252 administered in a fasted state
0
6
0
6
5
6
EG008
MK-7252 120 mg
Single oral dose of 120 mg of MK-7252 administered in a fasted state
0
8
0
8
6
8
EG009
MK-7252 162 mg
Single oral dose of 162 mg MK-7252 administered in a fasted state
0
6
0
6
4
6
EG010
MK-7252 180 mg
Single oral dose of 180 mg of MK-7252 administered in a fasted state
0
5
0
5
2
5
EG011
Placebo
Single oral dose of placebo to match MK-7252 administered in a fasted state
0
22
0
22
15
22
EG012
Post-Study
MK-7252 or placebo as a single dose in the post-study period administered in a fasted state
0
24
0
24
3
24
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0062 events2 affected12 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Postural orthostatic tachycardia syndrome
Cardiac disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Cerumen impaction
Ear and labyrinth disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Eye irritation
Eye disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Photophobia
Eye disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Abdominal discomfort
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Abdominal pain
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Diarrhoea
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Epigastric discomfort
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Flatulence
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0082 events2 affected8 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Gastrointestinal pain
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Mouth swelling
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Nausea
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0033 events2 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0112 events2 affected22 at risk
EG0120 events0 affected24 at risk
Vomiting
Gastrointestinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Catheter site haematoma
General disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Catheter site pain
General disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Chest discomfort
General disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Fatigue
General disorders
MedDRA 21.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Feeling of body temperature change
General disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected6 at risk
EG0052 events2 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Mucosal pain
General disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Angular cheilitis
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0121 events1 affected24 at risk
Cystitis
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Nasopharyngitis
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0122 events2 affected24 at risk
Oral herpes
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Pyuria
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0121 events1 affected24 at risk
Sinusitis
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Vulvovaginitis
Infections and infestations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Ligament sprain
Injury, poisoning and procedural complications
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Muscle contusion
Injury, poisoning and procedural complications
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Orthostatic heart rate response increased
Investigations
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0112 events2 affected22 at risk
EG0120 events0 affected24 at risk
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0062 events2 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0062 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0062 events2 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0121 events1 affected24 at risk
Myofascial pain syndrome
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected0 at risk
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Trismus
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Dizziness
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0032 events2 affected6 at risk
EG0040 events0 affected6 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0112 events2 affected22 at risk
EG0120 events0 affected24 at risk
Dizziness postural
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0062 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Dysgeusia
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Headache
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0001 events1 affected6 at risk
EG0013 events3 affected6 at risk
EG0022 events2 affected6 at risk
EG0032 events1 affected6 at risk
EG0043 events2 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0072 events2 affected6 at risk
EG0081 events1 affected8 at risk
EG0092 events2 affected6 at risk
EG0100 events0 affected5 at risk
EG0118 events8 affected22 at risk
EG0121 events1 affected24 at risk
Paraesthesia
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Presyncope
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Sensory loss
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Visual field defect
Nervous system disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0031 events1 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Irritability
Psychiatric disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0091 events1 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0081 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0022 events2 affected6 at risk
EG0031 events1 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Throat irritation
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Throat tightness
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0041 events1 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Cold sweat
Skin and subcutaneous tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0073 events3 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0112 events2 affected22 at risk
EG0120 events0 affected24 at risk
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0071 events1 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Erythema
Skin and subcutaneous tissue disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0111 events1 affected22 at risk
EG0120 events0 affected24 at risk
Hypertension
Vascular disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected12 at risk
EG0070 events0 affected6 at risk
EG0082 events1 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
Peripheral coldness
Vascular disorders
MedDRA 21.1
Systematic Assessment
EG0000 events0 affected6 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected12 at risk
EG0070 events0 affected6 at risk
EG0080 events0 affected8 at risk
EG0090 events0 affected6 at risk
EG0100 events0 affected5 at risk
EG0110 events0 affected22 at risk
EG0120 events0 affected24 at risk
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
6
OG0046
OG0056
OG00612
OG0076
OG0088
OG0096
OG0105
OG01122
0
OG0040
OG0050
OG0061
OG0070
OG0081
OG0090
OG0100
OG0110
5
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
288
(195 to 427)
OG003583(394 to 862)
OG0041190(805 to 1750)
OG0052040(1390 to 3000)
OG0065090(3460 to 7490)
OG0073500(2380 to 5160)
OG0086680(4530 to 9840)
OG0099840(6690 to 14500)
OG0107260(4930 to 10700)
OG0115520(3720 to 8170)
OG01210300(6970 to 15300)
6
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
559
(379 to 824)
OG0041150(781 to 1700)
OG0052030(1380 to 3000)
OG0065210(3530 to 7680)
OG0073490(2370 to 5150)
OG0086420(4350 to 9470)
OG0099530(6460 to 14100)
OG0107240(4900 to 10700)
OG0115510(3710 to 8200)
OG01210300(6910 to 15300)
6
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
558
(379 to 822)
OG0041140(775 to 1680)
OG0052020(1370 to 2980)
OG0065130(3480 to 7540)
OG0073450(2340 to 5070)
OG0086220(4220 to 9160)
OG0099240(6270 to 13600)
OG0107170(4860 to 10600)
OG0115480(3690 to 8130)
OG01210200(6840 to 15100)
6
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
543
(365 to 808)
OG0041130(757 to 1680)
OG0052030(1360 to 3020)
OG0065170(3470 to 7690)
OG0073420(2300 to 5090)
OG0086330(4250 to 9420)
OG0099750(6550 to 14500)
OG0107250(4860 to 10800)
OG0115500(3670 to 8260)
OG01210300(6860 to 15500)
6
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
220
(159 to 305)
OG004447(323 to 618)
OG005830(600 to 1150)
OG0061860(1340 to 2570)
OG0071380(997 to 1910)
OG0082290(1660 to 3170)
OG0093380(2440 to 4670)
OG0103160(2280 to 4380)
OG0112550(1820 to 3580)
OG0123880(2760 to 5440)
6
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
NA
(NA to NA)
Geometric least squares mean and 90% confidence interval were not calculated due to C12hr values for the 6 mg dose level being below the LLOQ (2.74 nmol/L).
OG003NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C12hr values for the 12 mg dose level being below the LLOQ (2.74 nmol/L).
OG0042.19(1.17 to 4.10)
OG0052.95(1.57 to 5.51)
OG00611.7(6.29 to 21.7)
OG0077.06(3.80 to 13.1)
OG00821.0(11.2 to 39.2)
OG00931.8(17.0 to 59.6)
OG01010.4(5.59 to 19.3)
OG0117.16(3.76 to 13.7)
OG01216.7(8.77 to 31.9)
6
OG0046
OG0056
OG0066
OG0076
OG0086
OG0096
OG0106
OG0115
OG0125
NA
(NA to NA)
Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 6 mg dose level being below the LLOQ (2.74 nmol/L).
OG003NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 12 mg dose level being below the LLOQ (2.74 nmol/L).
OG004NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 24 mg dose level being below the LLOQ (2.74 nmol/L).
OG005NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 48 mg dose level being below the LLOQ (2.74 nmol/L).
OG006NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 72 mg dose in level in Panel A being below the LLOQ (2.74 nmol/L).
OG007NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 72 mg dose level in Panel B being below the LLOQ (2.74 nmol/L).
OG008NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 108 mg dose level being below the LLOQ (2.74 nmol/L).
OG009NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 162 mg dose level being below the LLOQ (2.74 nmol/L).
OG010NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 120 mg dose level in Panel C Period 1 being below the LLOQ (2.74 nmol/L).
OG011NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 120 mg dose level in Panel C Period 2 being below the LLOQ (2.74 nmol/L).
OG012NA(NA to NA)Geometric least squares mean and 90% confidence interval were not calculated due to C24hr values for the 180 mg dose level in Panel C Period 3 being below the LLOQ (2.74 nmol/L).