Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| MK-8266-001 | Other Identifier | Merck protocol number | |
| 2009_700 | Other Identifier | Telerx ID | |
| 2009-015774-36 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A three panel study, to determine if MK-8266 given as a single dose is sufficiently safe and well tolerated. Panel A and B will consist of healthy young males and Panel C will consist of subjects with mild to moderate hypertension. The primary hypotheses for the study are that MK-8266 given as single doses is sufficiently safe and well tolerated to permit continued clinical investigation in healthy young male volunteers and male participants with mild-to-moderate hypertension and that in males with mild to moderate hypertension, at a single oral dose of MK-8266 that is sufficiently safe and well-tolerated, postdose mean time-weighted average across 24 hours of aortic augmentation index (TWA0-12hrs AIx) is reduced compared to placebo. A mean decrease of ≥ 5 percentage points is considered clinically meaningful.
Three panels, each consisting of either 8 or 9 participants (8 healthy young males in Panel A and Panel B; and 9 participants with mild to moderate hypertension in Panel C) will be randomized to receive either MK-8266 or matching placebo in either a 6:2 ratio (Panel A and Panel B) or 6:3 ratio (Panel C), respectively, in up to 5 treatment (1 to 5) periods in Panel A and up to 4 treatment (1 to 4) periods in Panel B and Panel C. In all panels, doses will be escalated in a rising, fixed sequence. Some participants took study drug after fasting and some with food.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Panel A, Healthy Male Participants, Sequence 1 | Experimental | MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: placebo/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
|
| Panel A, Healthy Male Participants, Sequence 2 | Experimental | MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: placebo/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
|
| Panel A, Healthy Male Participants, Sequence 3 | Experimental | MK-8266 in Period 1: 0.1 mg/ Period 2: placebo/ Period 3: 0.5/ Period 4: 1.0 mg/ Period 5: placebo. |
|
| Panel A, Healthy Male Participants, Sequence 4 | Experimental | MK-8266 in Period 1: placebo/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
|
| Panel B, Healthy Male Participants, Sequence 1 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8266 0.1 mg | Drug | Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form. Participants will fast for 8 hours prior to dosing. There will be at least a 7- day washout period between doses for any given participant. Some participants will receive study drug with food. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced One or More Adverse Events | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. | Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days) |
| Number of Participants Who Discontinued Study Drug Due to an AE | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. | Up to 43 days |
| Aortic Augmentation Index - Time-Weighted Average 0-24 Hours | Central ascending aortic blood pressure augmentation index (AIx) is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. AIx can be measured non-invasively by radial tonometry using aplanation tonometry of radial artery with the SphygmoCor Pulse Wave Analysis System Guide (SphygmoCor system). AIx was performed at prestudy to ensure an adequate waveform can be obtained. At each time point, a minimum of 2 AIx were completed in an attempt to obtain 2 acceptable quality assessments. A time weighted average was calculated. AIx was adjusted for heart rate. A decrease in the AIx of ≥5 percentage is considered clinically meaningful. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. The 12-hour measurement was not collected (per protocol) in all periods of Panels A and B. | Predose, 1.5, 3, 12, and 24 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Food on MK-8266 PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24hr) Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-24 hours] is a measure of the mean concentration levels of drug in the plasma after the dose. The Fed Group was administered a high fat meal. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
Not provided
Not provided
Not provided
Not provided
For Panel A, 5 treatment periods were planned in this study. For Panels B and C, only 4 treatment periods were planned.
Participants were recruited at 2 clinical study sites in Germany and in Belgium.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Panel A, Healthy Male Participants, Sequence 1 | MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: placebo/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
| FG001 | Panel A, Healthy Male Participants, Sequence 2 | MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: placebo/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
| FG002 | Panel A, Healthy Male Participants, Sequence 3 | MK-8266 in Period 1: 0.1 mg/ Period 2: placebo/ Period 3: 0.5/ Period 4: 1.0 mg/ Period 5: placebo. |
| FG003 | Panel A, Healthy Male Participants, Sequence 4 | MK-8266 in Period 1: placebo/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
| FG004 | Panel B, Healthy Male Participants, Sequence 1 | MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: placebo/ Period 4: 0.4 mg fed/ Period 5: na. |
| FG005 | Panel B, Healthy Male Participants, Sequence 2 | MK-8266 in Period 1: 0.4 mg/ Period 2: placebo/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na. |
| FG006 | Panel B, Healthy Male Participants, Sequence 3 | MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na. |
| FG007 | Panel B, Healthy Male Participants, Sequence 4 | MK-8266 in Period 1: placebo/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na. |
| FG008 | Panel C, Mild/Moderate Hypertension, Sequence 1 | Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
| FG009 | Panel C, Mild/Moderate Hypertension, Sequence 2 | Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na |
| FG010 | Panel C, Mild/Moderate Hypertension, Sequence 3 | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2 placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
| FG011 | Panel C, Mild/Moderate Hypertension, Sequence 4 | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na |
| FG012 | Panel C, Mild/Moderate Hypertension, Sequence 5 | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
| FG013 | Panel C, Mild/Moderate Hypertension, Sequence 6 | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: placebo/ Period 5: na |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Period 2 |
| |||||||||||||
| Period 3 |
| |||||||||||||
| Period 4 |
| |||||||||||||
| Period 5 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Panel A MK-8266 (Healthy Males) | MK-8266 single dose or placebo matching MK-8266 in healthy male participants in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose. |
| BG001 | Panel B MK-8266 (Healthy Males) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 One or More Adverse Events | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. | All participants who received at least one dose of the investigational drug. | Posted | Count of Participants | Participants | Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days) |
|
Up to 14 days after administration of the last dose of study drug (Up to 43 days)
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The analysis population consisted of all participants who received at least one dose of the investigational drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Panel A MK-8266 0.1 mg (Healthy Males) | MK-8266 single 0.1 mg dose in healthy male participants |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: placebo/ Period 4: 0.4 mg fed/ Period 5: na. |
|
| Panel B, Healthy Male Participants, Sequence 2 | Experimental | MK-8266 in Period 1: 0.4 mg/ Period 2: placebo/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na. |
|
| Panel B, Healthy Male Participants, Sequence 3 | Experimental | MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na. |
|
| Panel B, Healthy Male Participants, Sequence 4 | Experimental | MK-8266 in Period 1: placebo/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na. |
|
| Panel C, Mild/Moderate Hypertension, Sequence 1 | Experimental | Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
|
| Panel C, Mild/Moderate Hypertension, Sequence 2 | Experimental | Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na |
|
| Panel C, Mild/Moderate Hypertension, Sequence 3 | Experimental | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2 placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
|
| Panel C, Mild/Moderate Hypertension, Sequence 4 | Experimental | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na |
|
| Panel C, Mild/Moderate Hypertension, Sequence 5 | Experimental | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
|
| Panel C, Mild/Moderate Hypertension, Sequence 6 | Placebo Comparator | Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: placebo/ Period 5: na |
|
|
|
| MK-8266 1.0 mg | Drug | MK-8266 1.0 mg oral capsule. Participants will fast for 8 hours prior to dosing. There will be at least a 7- day washout period between doses for any given participant. |
|
| Placebo | Drug | Placebo to match MK-8266 0.1 or 1.0 mg. Participants will fast for 8 hours prior to dosing. There will be at least a 7- day washout period between doses for any given participant. |
|
| MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-inf] is a measure of the mean concentration levels of drug in the plasma after the dose. AUC[0-inf] was not collected, analyzed or summarized for participants receiving placebo. | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
| MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. For Panel A 1.0/0.8 mg MK-8266, the second dose was not well characterized due to limited sampling. Observed exposure likely underestimates the true exposure. Cmax was not collected, analyzed or summarized for participants receiving placebo. | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
| MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Tmax was not collected, analyzed or summarized for participants receiving placebo. | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
| MK-8266 PK Parameter Apparent t1/2 | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. t1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. Harmonic means +/- Pseudo standard deviations are displayed. t1/2 was not collected, analyzed or summarized for participants receiving placebo. | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
| Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose |
| Effect of Food on MK-8266 PK Parameter Cmax Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. The Fed Group was administered a high fat meal. | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
| Time-Weighted Average of Heart Rate (0-12 Hours) | HR was measured with a validated automatic measuring device. Time weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. | Up to 12 hours |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
MK-8266 single dose or placebo matching MK-8266 in healthy male participants in Periods 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na. |
| BG002 | Panel C MK-8266 (Mild/Mod. Hypertension) | MK-8266 single dose or placebo matching MK-8266 (Mild/Mod. Hypertension) in Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Panel A MK-8266 0.2 mg (Healthy Males) | MK-8266 single 0.2 mg dose in healthy male participants |
| OG002 | Panel A MK-8266 0.5 mg (Healthy Males) | MK-8266 single 0.5 mg dose in healthy male participants |
| OG003 | Panel A MK-8266 1.0 mg (Healthy Males) | MK-8266 single 1.0 mg dose in healthy male participants |
| OG004 | Panel A MK-8266 1.0/0.8 mg (Healthy Males) | MK-8266 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants |
| OG005 | Panel B MK-8266 0.4 mg (Healthy Males) | MK-8266 single dose 0.4 mg in healthy male participants |
| OG006 | Panel B MK-8266 1.2 mg (Healthy Males) | MK- 8266 single dose 1.2 mg in healthy male participants |
| OG007 | Panel B MK-8266 1.2/0.6 mg (Healthy Males) | MK-8266 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male |
| OG008 | Panel B MK-8266 0.4 mg Fed (Healthy Males) | MK-8266 single 0.4 mg dose in healthy male participants, fed. |
| OG009 | Panel C MK-8266 1.0/0.8 mg (Mild/Mod. Hypertension) | MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension |
| OG010 | Panel C MK-8266 1.2/1.0 mg (Mild/Mod. Hypertension) | MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension |
| OG011 | Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) | MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension |
| OG012 | Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) | MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension |
| OG013 | Pooled Placebo (Panels A, B, C) | Placebo matching MK-8266. |
|
|
| Primary | Number of Participants Who Discontinued Study Drug Due to an AE | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. | All participants who received at least one dose of the investigational drug. | Posted | Count of Participants | Participants | Up to 43 days |
|
|
|
| Primary | Aortic Augmentation Index - Time-Weighted Average 0-24 Hours | Central ascending aortic blood pressure augmentation index (AIx) is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. AIx can be measured non-invasively by radial tonometry using aplanation tonometry of radial artery with the SphygmoCor Pulse Wave Analysis System Guide (SphygmoCor system). AIx was performed at prestudy to ensure an adequate waveform can be obtained. At each time point, a minimum of 2 AIx were completed in an attempt to obtain 2 acceptable quality assessments. A time weighted average was calculated. AIx was adjusted for heart rate. A decrease in the AIx of ≥5 percentage is considered clinically meaningful. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. The 12-hour measurement was not collected (per protocol) in all periods of Panels A and B. | All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment. Panel B MK-8266 0.4 mg fasted and Panel B MK-8266 0.4 mg fed were combined in the analysis. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis. | Posted | Least Squares Mean | Standard Deviation | Percentage of central pulse pressure | Predose, 1.5, 3, 12, and 24 hours postdose |
|
|
|
|
| Primary | MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-inf] is a measure of the mean concentration levels of drug in the plasma after the dose. AUC[0-inf] was not collected, analyzed or summarized for participants receiving placebo. | AUC[0-inf] was not estimated at MK-8266 doses <1.0 mg and for the first 2 doses in Panel C due to the lack of measureable concentrations, and for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis. | Posted | Mean | Standard Deviation | mg/mL*hr | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
|
|
|
| Primary | MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. For Panel A 1.0/0.8 mg MK-8266, the second dose was not well characterized due to limited sampling. Observed exposure likely underestimates the true exposure. Cmax was not collected, analyzed or summarized for participants receiving placebo. | All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment, according to the underlying scientific model. Cmax was not estimated for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis. | Posted | Mean | Standard Deviation | nM | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
|
|
|
| Primary | MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Tmax was not collected, analyzed or summarized for participants receiving placebo. | The analysis population consisted of participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment. Tmax was not estimated for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis. | Posted | Median | Full Range | Hours | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
|
|
|
| Primary | MK-8266 PK Parameter Apparent t1/2 | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. t1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. Harmonic means +/- Pseudo standard deviations are displayed. t1/2 was not collected, analyzed or summarized for participants receiving placebo. | t1/2 was not estimated at MK-8266 doses below 1 mg and for the first 2 doses in Panel C due to the lack of measureable concentrations and for participants receiving placebo. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis. | Posted | Mean | Standard Deviation | Hours | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
|
|
|
| Secondary | Effect of Food on MK-8266 PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24hr) Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-24 hours] is a measure of the mean concentration levels of drug in the plasma after the dose. The Fed Group was administered a high fat meal. | All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment, according to the underlying scientific model. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | nM·hr | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose |
|
|
|
|
| Secondary | Effect of Food on MK-8266 PK Parameter Cmax Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. The Fed Group was administered a high fat meal. | All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment, according to the underlying scientific model. | Posted | Geometric Least Squares Mean | 95% Confidence Interval | nM | Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose |
|
|
|
|
| Secondary | Time-Weighted Average of Heart Rate (0-12 Hours) | HR was measured with a validated automatic measuring device. Time weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period. | All participants who complied with the protocol sufficiently to ensure that their data likely exhibited the effects of treatment. Panel B MK-8266 0.4 mg fasted and Panel B MK-8266 0.4 mg fed were combined in the analysis. One participant in Panel B 1.2 mg + 0.6 mg did not receive the 1.2 mg dose and was not included in this analysis. | Posted | Least Squares Mean | Standard Error | Beats per Minute | Up to 12 hours |
|
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | Panel A MK-8266 0.2 mg (Healthy Males) | MK-8266 single 0.2 mg dose in healthy male participants | 0 | 6 | 0 | 6 | 3 | 6 |
| EG002 | Panel A MK-8266 0.5 mg (Healthy Males) | MK-8266 single 0.5 mg dose in healthy male participants | 0 | 6 | 0 | 6 | 5 | 6 |
| EG003 | Panel A MK-8266 1.0 mg (Healthy Males) | MK-8266 single 1.0 mg dose in healthy male participants | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Panel A MK-8266 1.0/0.8 mg (Healthy Males) | MK-8266 single 1.0 mg dose followed in 6 hours by a 0.8 mg dose in healthy male participants | 0 | 6 | 0 | 6 | 3 | 6 |
| EG005 | Panel B MK-8266 0.4 mg (Healthy Males) | MK-8266 single dose 0.4 mg in healthy male participants | 0 | 6 | 0 | 6 | 1 | 6 |
| EG006 | Panel B MK-8266 1.2 mg (Healthy Males) | MK- 8266 single dose 1.2 mg in healthy male participants | 0 | 6 | 0 | 6 | 4 | 6 |
| EG007 | Panel B MK-8266 1.2/0.6 mg (Healthy Males) | MK-8266 single 1.2 mg followed in 6 hours by a 0.6 mg dose in healthy male participants | 0 | 6 | 0 | 6 | 3 | 6 |
| EG008 | Panel B MK-8266 0.4 mg Fed (Healthy Males) | MK-8266 single 0.4 mg dose in healthy male participants, fed. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG009 | Panel C MK-8266 1.0/0.8 mg (Mild/Mod. Hypertension) | MK-8266 single 1.0 mg dose followed in 8 hours by a 0.8 mg dose in participants with mild/mod. hypertension | 0 | 6 | 0 | 6 | 3 | 6 |
| EG010 | Panel C MK-8266 1.2/1.0 mg (Mild/Mod. Hypertension) | MK-8266 single 1.2 mg dose followed in 8 hours by a 1.0 mg dose in participants with mild/mod. hypertension | 0 | 6 | 0 | 6 | 4 | 6 |
| EG011 | Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) | MK-8266 single 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension | 0 | 6 | 0 | 6 | 6 | 6 |
| EG012 | Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) | MK-8266 single 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose in participants with mild/mod. hypertension | 0 | 6 | 0 | 6 | 3 | 6 |
| EG013 | Pooled Placebo (Panels A, B, C) | Placebo matching MK-8266. | 0 | 23 | 0 | 23 | 10 | 23 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Bacterial test positive | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Blood pressure systolic increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Blood urine present | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Orthostatic heart rate response increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
|
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
| 0.2 mg vs. placebo |
| -1.23 |
| 2-Sided |
| 90 |
| -5.42 |
| 2.96 |
| Other |
| ANOVA | 0.498 | 0.5 mg vs. placebo | 0.01 | 2-Sided | 90 | -4.05 | 4.06 | Other |
| ANOVA | 0.012 | 1 mg vs. placebo | -5.69 | 2-Sided | 90 | -9.74 | -1.63 | Other |
| ANOVA | 0.059 | 1 mg + 0.8 mg vs. placebo | -3.97 | 2-Sided | 90 | -8.16 | 0.22 | Other |
| ANOVA | 0.191 | 0.4 mg vs. placebo | 2.22 | 2-Sided | 90 | -2.09 | 6.54 | Other |
| ANOVA | 0.333 | 1.2 mg vs. placebo | 1.24 | 2-Sided | 90 | -3.67 | 6.15 | Other |
| ANOVA | 0.314 | 1.2 mg + 0.6 mg vs. placebo | -1.43 | 2-Sided | 90 | -6.50 | 3.63 | Other |
| ANOVA | 0.001 | 1 mg + 0.8 mg vs. placebo | -9.31 | 2-Sided | 90 | -14.2 | -4.37 | Other |
| ANOVA | 0.017 | 1.2 mg + 1.0 mg vs. placebo | -6.45 | 2-Sided | 90 | -11.4 | -1.51 | Other |
| ANOVA | 0.001 | 1.0 mg + 0.6 mg + 0.6 mg vs. placebo | -9.96 | 2-Sided | 90 | -14.9 | -5.02 | Other |
| ANOVA | 0.002 | 1 mg + 1 mg + 0.6 mg vs. placebo | -9.00 | 2-Sided | 95 | -13.8 | -4.17 | Other |
| 0.2 mg vs. placebo |
| 2.33 |
| 2-Sided |
| 90 |
| -1.17 |
| 5.83 |
| Other |
| ANOVA | 0.0741 | 0.5mg vs. placebo | -2.96 | 2-Sided | 90 | -6.35 | 0.43 | Other |
| ANOVA | <0.001 | 1 mg vs. placebo | 7.08 | 2-Sided | 90 | 3.69 | 10.47 | Other |
| ANOVA | 0.0211 | 1 mg + 0.8 mg vs. placebo | 4.39 | 2-Sided | 90 | 0.89 | 7.09 | Other |
| ANOVA | 0.399 | 0.4 mg vs. placebo | 0.85 | 2-Sided | 90 | -4.79 | 6.48 | Other |
| ANOVA | 0.100 | 1.2 mg vs. placebo | 4.54 | 2-Sided | 90 | -1.94 | 11.02 | Other |
| ANOVA | 0.195 | 1.2 mg + 0.6 mg vs. placebo | 3.38 | 2-Sided | 90 | -3.29 | 10.06 | Other |
| ANOVA | 0.022 | 1.0 mg + 0.8 mg vs. placebo | 9.16 | 2-Sided | 90 | 1.74 | 16.58 | Other |
| ANOVA | 0.098 | 1.2 mg + 1.0 mg vs. placebo | 5.74 | 2-Sided | 90 | -1.68 | 13.16 | Other |
| ANOVA | 0.214 | 1 mg + 0.6 mg + 0.6 mg vs. placebo | 3.48 | 2-Sided | 90 | -3.94 | 10.90 | Other |
| ANOVA | 0.163 | 1 mg + 1 mg + 0.6 mg vs. placebo | 4.24 | 2-Sided | 95 | -3.03 | 11.52 | Other |