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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01025791

2009-015774-36 (EudraCT Number)

8266-001

2009_700 (Other Identifier)

MK-8266-001 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Double Blind

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25 participants in 14 patient groups, including a placebo group

Panel A, Healthy Male Participants, Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel A, Healthy Male Participants, Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel A, Healthy Male Participants, Sequence 3

Experimental group

Description:

MK-8266 in Period 1: 0.1 mg/ Period 2: placebo/ Period 3: 0.5/ Period 4: 1.0 mg/ Period 5: placebo.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel A, Healthy Male Participants, Sequence 4

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel B, Healthy Male Participants, Sequence 1

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel B, Healthy Male Participants, Sequence 2

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel B, Healthy Male Participants, Sequence 3

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: MK-8266 0.1 mg

Panel B, Healthy Male Participants, Sequence 4

Experimental group

Description:

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.

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel C, Mild/Moderate Hypertension, Sequence 1

Experimental group

Description:

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

Treatment:

Drug: MK-8266 1.0 mg

Drug: MK-8266 0.1 mg

Panel C, Mild/Moderate Hypertension, Sequence 2

Experimental group

Description:

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

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel C, Mild/Moderate Hypertension, Sequence 3

Experimental group

Description:

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

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel C, Mild/Moderate Hypertension, Sequence 4

Experimental group

Description:

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

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg

Panel C, Mild/Moderate Hypertension, Sequence 5

Experimental group

Description:

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

Treatment:

Drug: MK-8266 1.0 mg

Drug: MK-8266 0.1 mg

Panel C, Mild/Moderate Hypertension, Sequence 6

Placebo Comparator group

Description:

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

Treatment:

Drug: MK-8266 1.0 mg

Drug: Placebo

Drug: MK-8266 0.1 mg