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A Single Dose Study of MK-8266 (MK-8266-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01025791
Recruitment Status : Completed
First Posted : December 4, 2009
Results First Posted : February 20, 2019
Last Update Posted : February 20, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: MK-8266 0.1 mg Drug: MK-8266 1.0 mg Drug: Placebo Phase 1

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266
Actual Study Start Date : November 18, 2009
Actual Primary Completion Date : May 14, 2010
Actual Study Completion Date : May 14, 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Experimental: 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.
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Experimental: 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
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.

Experimental: 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
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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 Comparator: 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
Drug: MK-8266 0.1 mg
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.
Other Name: MK-8266

Drug: MK-8266 1.0 mg
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.

Drug: Placebo
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.




Primary Outcome Measures :
  1. Number of Participants Who Experienced One or More Adverse Events [ Time Frame: Up to 14 days after administration of last dose of study drug in each study period (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. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.

  2. Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: 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. Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.

  3. Aortic Augmentation Index - Time-Weighted Average 0-24 Hours [ Time Frame: Predose, 1.5, 3, 12, and 24 hours postdose ]
    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.

  4. MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [ Time Frame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose ]
    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.

  5. MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax) [ Time Frame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose ]
    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.

  6. MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax) [ Time Frame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose ]
    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.

  7. MK-8266 PK Parameter Apparent t1/2 [ Time Frame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose ]
    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.

  2. 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 [ Time Frame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose ]
    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.

  3. Time-Weighted Average of Heart Rate (0-12 Hours) [ Time Frame: Up to 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • For Panel A and B Participant is a healthy male between 18 to 45 years of age. For Panel C Participant is a male with essential hypertension between 18 to 55 years of age
  • A non-smoker

Exclusion Criteria:

  • Has a history of stroke, chronic seizure or major neurological disorder
  • Has a disability that can interfere with rising from a sitting position to the standing position
  • Has a personal of family history of bleeding or clotting disorders
  • Has a history of cancer
  • Is unable to refrain from or anticipates the use of any prescription or nonprescription drug during the study
  • Consumes excessive amounts of caffeine or alcohol
  • Has had major surgery, donated blood or participated in another investigational study in the past 4 weeks

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01025791


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01025791    
Other Study ID Numbers: 8266-001
MK-8266-001 ( Other Identifier: Merck protocol number )
2009_700 ( Other Identifier: Telerx ID )
2009-015774-36 ( EudraCT Number )
First Posted: December 4, 2009    Key Record Dates
Results First Posted: February 20, 2019
Last Update Posted: February 20, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases