Safety, Pharmacodynamics, and Pharmacokinetics of Different Dosing Regimens of MK-8266 in Participants With Hypertension (MK-8266-008)

NCT ID: NCT01244035

Last Updated: 2019-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-19
• Study Completion Date: 2010-12-23

Brief Summary

This was designed as a two part study comprising sequential double-dummy, placebo controlled 3-period randomized crossover studies. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of different doses and dose regimens of MK-8266. Only Part I of the study was completed.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part I - Sequence ABC

Treatment A in Period 1, Treatment B in Period 2, and Treatment C in Period 3

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment B

Intervention Type: DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment C

Intervention Type: DRUG

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part I - Sequence ACB

Treatment A in Period 1, Treatment C in Period 2, and Treatment B in Period 3

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment B

Intervention Type: DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment C

Intervention Type: DRUG

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part I - Sequence BCA

Treatment B in Period 1, Treatment C in Period 2, and Treatment A in Period 3

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment B

Intervention Type: DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment C

Intervention Type: DRUG

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part I - Sequence BAC

Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment B

Intervention Type: DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment C

Intervention Type: DRUG

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part I - Sequence CAB

Treatment C in Period 1, Treatment A in Period 2, and Treatment B in Period 3

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment B

Intervention Type: DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment C

Intervention Type: DRUG

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part I - Sequence CBA

Treatment C in Period 1, Treatment B in Period 2, and Treatment A in Period 3

Group Type: EXPERIMENTAL

Treatment A

Intervention Type: DRUG

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment B

Intervention Type: DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment C

Intervention Type: DRUG

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part II - Sequence DEF

Treatment D in Period 1, Treatment E in Period 2, and Treatment F in Period 3

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Intervention Type: DRUG

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Intervention Type: DRUG

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part II - Sequence DFE

Treatment D in Period 1, Treatment F in Period 2, and Treatment E in Period 3

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Intervention Type: DRUG

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Intervention Type: DRUG

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part II - Sequence EFD

Treatment E in Period 1, Treatment F in Period 2, and Treatment D in Period 3

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Intervention Type: DRUG

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Intervention Type: DRUG

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part II - Sequence EDF

Treatment E in Period 1, Treatment D in Period 2, and Treatment F in Period 3

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Intervention Type: DRUG

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Intervention Type: DRUG

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part II - Sequence FDE

Treatment F in Period 1, Treatment D in Period 2, and Treatment E in Period 3

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Intervention Type: DRUG

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Intervention Type: DRUG

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Part II -Sequence FED

Treatment F in Period 1, Treatment E in Period 2, and Treatment D in Period 3

Group Type: EXPERIMENTAL

Treatment D

Intervention Type: DRUG

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Intervention Type: DRUG

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Intervention Type: DRUG

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Interventions

Treatment A

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Intervention Type: DRUG

Treatment B

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Intervention Type: DRUG

Treatment C

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Intervention Type: DRUG

Treatment D

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Intervention Type: DRUG

Treatment E

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Intervention Type: DRUG

Treatment F

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Intervention Type: DRUG

Other Intervention Names

MK-8266 1.3 mg BID; MK-8266 0.9 mg FDD; Placebo

Eligibility Criteria

Inclusion Criteria

• Participant has essential hypertension who is in grade 1 or 2 hypertension according to the European Society of Hypertension (ESH) as delineated in the European Society of Cardiology (ESC) 2007 guidelines, i.e. systolic blood pressure values of 140-179 and diastolic blood pressure values of 90-109 on at least 3 occasions prior to the study.
• Otherwise healthy participants with grade 1 or 2 arterial hypertension who are treated with a single antihypertensive drug and meet the above blood pressure criteria may be enrolled at the discretion of the investigator
• Participant is generally in good health with the exception of hypertension
• Participant is a nonsmoker and/or has not used nicotine or nicotine-containing products for 6 months

Exclusion Criteria

• Participant has a history of any illness that might confound the results of the study or pose and additional risk to the participant if they take part in the study
• Participant has a history of stroke, chronic seizures, or major neurological disorder
• Participant has a disability that can interfere with rising from a semi-recumbent position to the standing position
• Participant has a personal or family history of a bleeding or clotting disorder
• Participant has a history of frequent nosebleeds or recurrent or active gingivitis
• Participant has a history of cancer, except 1) certain skin cancers; 2) cancer successfully treated more than 10 years prior to the study that has not recurred; or, 3) participants who are unlikely to have a recurrence during the study
• Participant has a history of cardiac disease including but not limited to heart valve disease or evidence of secondary cardiac damage
• Participant is categorized as class II or greater according to the New York Heart Association (NYHA) functional classification for heart failure
• Participant is unable to refrain from use of prescription or non-prescription drugs or herbal remedies (such as St. John's Wort) during the study
• Participant anticipates using phosphodiesterase (PDE5) inhibitors [sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®)] during the study
• Participant consumes excessive amounts of alcohol (more than 3 drinks per day) or caffeine (more than 6 servings a day)
• Participant has had major surgery, donated or lost 1 unit of blood, or participated in another investigational within 4 weeks prior to the study
• Participant has a history of multiple and/or severe allergies, or has had an anaphylactic reaction or intolerance to any drugs or food

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

2010-021832-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8266-008

Identifier Type: -

Identifier Source: org_study_id