HypertensionPhase 1NCT01025791

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

A Phase 1 study testing MK-8266 0.1 mg and MK-8266 1.0 mg in people with Hypertension, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for: Hypertension
What is being tested?: MK-8266 0.1 mg and MK-8266 1.0 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 25 participants
Where: No sites listed yet
Study dates: 18 Nov 2009to 14 May 2010
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
Men only
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

About this study

Official title: A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266

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.

Read the 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.

Conditions: Hypertension
Being tested: MK-8266 0.1 mg, MK-8266 1.0 mg, Placebo
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-8266 0.1 mgDrug
Also called MK-8266
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.
MK-8266 1.0 mgDrug
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.
PlaceboDrug
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.

Study groups in NCT01025791
Study group	Role	What they receive
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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: 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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
Panel B, Healthy Male Participants, Sequence 1	Experimental	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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg
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. Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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 Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg
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 Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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 Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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 Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo
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 Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg
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 Receives: Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Predose, 1.5, 3, 12, and 24 hours postdose
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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.
Measured: Up to 12 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Nov 200914 May 2010

First posted4 Dec 2009 (estimated)
Study start18 Nov 2009
Primary completion14 May 2010
Study completion14 May 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HypertensionStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01025791
Sponsor's protocol ID: 8266-001
Other IDs: MK-8266-001, 2009_700, 2009-015774-36, 2009
Status last verified: Oct 2018
First submitted: 3 Dec 2009
Last updated: 20 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266
ClinicalTrials.gov ID: NCT01025791
Acronym / sponsor ID: 8266-001
Conditions: Hypertension
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 18 Nov 2009 (actual)
Primary completion: 14 May 2010 (actual)
Study completion: 14 May 2010 (actual)
First posted: 4 Dec 2009 (estimated)
Results: Posted 20 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Double blind (participant, investigator)
Number of arms: 14

Arm	Type	Receives
Panel A, Healthy Male Participants, Sequence 1	Experimental	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mgMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboMK-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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mgPeriod 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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboPeriod 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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboPeriod 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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboPeriod 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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mgPeriod 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	Drug: MK-8266 0.1 mg, Drug: MK-8266 1.0 mg, Drug: PlaceboPeriod 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

Who may qualify

Ages: 18 to 55 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-8266 0.1 mgAlso: MK-8266Single 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.	Drug	Panel A, Healthy Male Participants, Sequence 1, Panel A, Healthy Male Participants, Sequence 2, Panel A, Healthy Male Participants, Sequence 3, Panel A, Healthy Male Participants, Sequence 4, Panel B, Healthy Male Participants, Sequence 1, Panel B, Healthy Male Participants, Sequence 2, Panel B, Healthy Male Participants, Sequence 3, Panel B, Healthy Male Participants, Sequence 4, Panel C, Mild/Moderate Hypertension, Sequence 1, Panel C, Mild/Moderate Hypertension, Sequence 2, Panel C, Mild/Moderate Hypertension, Sequence 3, Panel C, Mild/Moderate Hypertension, Sequence 4, Panel C, Mild/Moderate Hypertension, Sequence 5, Panel C, Mild/Moderate Hypertension, Sequence 6
MK-8266 1.0 mgMK-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	Panel A, Healthy Male Participants, Sequence 1, Panel A, Healthy Male Participants, Sequence 2, Panel A, Healthy Male Participants, Sequence 3, Panel A, Healthy Male Participants, Sequence 4, Panel B, Healthy Male Participants, Sequence 1, Panel B, Healthy Male Participants, Sequence 2, Panel B, Healthy Male Participants, Sequence 3, Panel B, Healthy Male Participants, Sequence 4, Panel C, Mild/Moderate Hypertension, Sequence 1, Panel C, Mild/Moderate Hypertension, Sequence 2, Panel C, Mild/Moderate Hypertension, Sequence 3, Panel C, Mild/Moderate Hypertension, Sequence 4, Panel C, Mild/Moderate Hypertension, Sequence 5, Panel C, Mild/Moderate Hypertension, Sequence 6
PlaceboPlacebo 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.	Drug	Panel A, Healthy Male Participants, Sequence 1, Panel A, Healthy Male Participants, Sequence 2, Panel A, Healthy Male Participants, Sequence 3, Panel A, Healthy Male Participants, Sequence 4, Panel B, Healthy Male Participants, Sequence 1, Panel B, Healthy Male Participants, Sequence 2, Panel B, Healthy Male Participants, Sequence 4, Panel C, Mild/Moderate Hypertension, Sequence 2, Panel C, Mild/Moderate Hypertension, Sequence 3, Panel C, Mild/Moderate Hypertension, Sequence 4, Panel C, Mild/Moderate Hypertension, Sequence 6

Primary outcome

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.
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.
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.
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.
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.
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.
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.

3 secondary outcomes

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
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
Time-Weighted Average of Heart Rate (0-12 Hours)
Time frame: Up to 12 hours

Results and safety

Results posted to the registry on 20 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Panel A, Healthy Male Participants, Sequence 1	2	2
Panel A, Healthy Male Participants, Sequence 2	2	2
Panel A, Healthy Male Participants, Sequence 3	2	2
Panel A, Healthy Male Participants, Sequence 4	2	2
Panel B, Healthy Male Participants, Sequence 1	2	2
Panel B, Healthy Male Participants, Sequence 2	2	2
Panel B, Healthy Male Participants, Sequence 3	2	2
Panel B, Healthy Male Participants, Sequence 4	2	2
Panel C, Mild/Moderate Hypertension, Sequence 1	2	2
Panel C, Mild/Moderate Hypertension, Sequence 2	1	1
Panel C, Mild/Moderate Hypertension, Sequence 3	2	2
Panel C, Mild/Moderate Hypertension, Sequence 4	1	1
Panel C, Mild/Moderate Hypertension, Sequence 5	2	2
Panel C, Mild/Moderate Hypertension, Sequence 6	1	1

Primary outcome: 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). Count of participants. Unit: Participants

Measure	Panel A MK-8266 0.1 mg (Healthy Males) n = 6	Panel A MK-8266 0.2 mg (Healthy Males) n = 6	Panel A MK-8266 0.5 mg (Healthy Males) n = 6	Panel A MK-8266 1.0 mg (Healthy Males) n = 6	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n = 6	Panel B MK-8266 0.4 mg (Healthy Males) n = 6	Panel B MK-8266 1.2 mg (Healthy Males) n = 6	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n = 6	Panel B MK-8266 0.4 mg Fed (Healthy Males) n = 6	Panel C MK-8266 1.0/0.8 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.2/1.0 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n = 6	Pooled Placebo (Panels A, B, C) n = 23
Value	2	3	5	2	3	1	4	3	2	3	4	6	3	10

Population analysed: All participants who received at least one dose of the investigational drug.

Primary outcome: Number of Participants Who Discontinued Study Drug Due to an AE

Time frame: Up to 43 days. Count of participants. Unit: Participants

Measure	Panel A MK-8266 0.1 mg (Healthy Males) n = 6	Panel A MK-8266 0.2 mg (Healthy Males) n = 6	Panel A MK-8266 0.5 mg (Healthy Males) n = 6	Panel A MK-8266 1.0 mg (Healthy Males) n = 6	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n = 6	Panel B MK-8266 0.4 mg (Healthy Males) n = 6	Panel B MK-8266 1.2 mg (Healthy Males) n = 6	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n = 6	Panel B MK-8266 0.4 mg Fed (Healthy Males) n = 6	Panel C MK-8266 1.0/0.8 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.2/1.0 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n = 6	Pooled Placebo (Panels A, B, C) n = 23
Value	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Population analysed: All participants who received at least one dose of the investigational drug.

Primary outcome: Aortic Augmentation Index - Time-Weighted Average 0-24 Hours

Time frame: Predose, 1.5, 3, 12, and 24 hours postdose. Least squares mean (Standard Deviation). Unit: Percentage of central pulse pressure

Measure	Panel A MK-8266 0.1 mg (Healthy Males) n = 6	Panel A MK-8266 0.2 mg (Healthy Males) n = 6	Panel A MK-8266 0.5 mg (Healthy Males) n = 6	Panel A MK-8266 1.0 mg (Healthy Males) n = 6	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n = 6	Panel A Placebo n = 10	Pooled Panel B MK-8266 0.4 mg (Healthy Males) n = 12	Panel B MK-8266 1.2 mg (Healthy Males) n = 6	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n = 5	Panel B Placebo n = 8	Panel C MK-8266 1.0/0.8 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.2/1.0 mg (Mild/Mod. Hypertension) n = 6	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. n = 6	Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n = 6	Panel C Placebo n = 12
Value	-8.79 (9.66)	-2.96 (9.15)	-1.73 (4.49)	-7.42 (3.85)	-5.70 (7.57)	-1.73 (7.36)	-13.1 (8.71)	-14.1 (7.49)	-16.7 (5.21)	-15.3 (2.68)	8.43 (4.98)	11.29 (6.60)	7.78 (11.10)	8.74 (3.90)	17.74 (6.75)

Panel A MK-8266 0.1 mg (Healthy Males) vs Panel A Placebo: 0.1 mg vs. placebo: -7.06 (90% CI -11.1 to -3.00), p = 0.003, ANOVA
Panel A MK-8266 0.2 mg (Healthy Males) vs Panel A Placebo: 0.2 mg vs. placebo: -1.23 (90% CI -5.42 to 2.96), p = 0.310, ANOVA
Panel A MK-8266 0.5 mg (Healthy Males) vs Panel A Placebo: 0.5 mg vs. placebo: 0.01 (90% CI -4.05 to 4.06), p = 0.498, ANOVA

Population analysed: 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.

Primary outcome: 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. Mean (Standard Deviation). Unit: mg/mL*hr

Measure	Panel A MK-8266 0.1 mg (Healthy Males) n = 0	Panel A MK-8266 0.2 mg (Healthy Males) n = 0	Panel A MK-8266 0.5 mg (Healthy Males) n = 0	Panel A MK-8266 1.0 mg (Healthy Males) n = 6	Panel A MK-8266 1.0/0.8 mg (Healthy Males) n = 6	Panel B MK-8266 0.4 mg (Healthy Males) n = 0	Panel B MK-8266 1.2 mg (Healthy Males) n = 6	Panel B MK-8266 1.2/0.6 mg (Healthy Males) n = 5	Panel B MK-8266 0.4 mg Fed (Healthy Males) n = 0	Panel C MK- 8266 1.0/0.8 mg (Mild/Mod. Hypertension) n = 0	Panel C MK- 8266 1.2/1.0 mg (Mild/Mod. Hypertension) n = 0	Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension) n = 6	Panel C MK- 8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension) n = 6
Value	–	–	–	264 (64.4)	441 (105)	–	216 (55.95)	350 (49.5)	–	–	–	528 (151)	623 (350)

Population analysed: 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.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days after administration of the last dose of study drug (Up to 43 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Panel A MK-8266 0.1 mg (Healthy Males)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Panel A MK-8266 0.2 mg (Healthy Males)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Panel A MK-8266 0.5 mg (Healthy Males)	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Panel A MK-8266 1.0 mg (Healthy Males)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Panel A MK-8266 1.0/0.8 mg (Healthy Males)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Panel B MK-8266 0.4 mg (Healthy Males)	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Panel B MK-8266 1.2 mg (Healthy Males)	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Panel B MK-8266 1.2/0.6 mg (Healthy Males)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Panel B MK-8266 0.4 mg Fed (Healthy Males)	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Panel C MK-8266 1.0/0.8 mg (Mild/Mod. Hypertension)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Panel C MK-8266 1.2/1.0 mg (Mild/Mod. Hypertension)	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Panel C MK-8266 1.0/0.6/0.6 mg (Mild/Mod. Hypertension)	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Panel C MK-8266 1.0/1.0/0.6 mg (Mild/Mod. Hypertension)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Pooled Placebo (Panels A, B, C)	0 of 23 (0%)	10 of 23 (43.5%)	0 of 23

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-8266 0.1 mg and MK-8266 1.0 mg in people with Hypertension, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01025791.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2019.