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

NCT01025791 | Completed Phase 1 Results

• 4 other identifiers: 8266-001MK-8266-0012009_7002009-015774-36
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (7)

• 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

• 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

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

  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

  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)

  Up to 12 hours

Study Arms (14)

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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

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

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

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

Drug: MK-8266 0.1 mg; Drug: MK-8266 1.0 mg; Drug: Placebo

Interventions

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.

Also known as: MK-8266

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 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.

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

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.

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2009
• First Posted: December 4, 2009
• Study Start: November 18, 2009
• Primary Completion: May 14, 2010
• Study Completion: May 14, 2010
• Last Updated: February 20, 2019
• Results First Posted: February 20, 2019

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share