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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: Treatment D; Drug: Treatment B; Drug: Treatment C; Drug: Treatment F; Drug: Treatment A; Drug: Treatment E

Study type: Interventional

Funder types: Industry

Identifiers

NCT01244035

8266-008

2010-021832-32 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: Male

Ages: 21 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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31 participants in 12 patient groups

Part I - Sequence ABC

Experimental group

Description:

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

Treatment:

Drug: Treatment A

Drug: Treatment C

Drug: Treatment B

Part I - Sequence ACB

Experimental group

Description:

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

Treatment:

Drug: Treatment A

Drug: Treatment C

Drug: Treatment B

Part I - Sequence BCA

Experimental group

Description:

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

Treatment:

Drug: Treatment A

Drug: Treatment C

Drug: Treatment B

Part I - Sequence BAC

Experimental group

Description:

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

Treatment:

Drug: Treatment A

Drug: Treatment C

Drug: Treatment B

Part I - Sequence CAB

Experimental group

Description:

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

Treatment:

Drug: Treatment A

Drug: Treatment C

Drug: Treatment B

Part I - Sequence CBA

Experimental group

Description:

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

Treatment:

Drug: Treatment A

Drug: Treatment C

Drug: Treatment B

Part II - Sequence DEF

Experimental group

Description:

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

Treatment:

Drug: Treatment E

Drug: Treatment F

Drug: Treatment D

Part II - Sequence DFE

Experimental group

Description:

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

Treatment:

Drug: Treatment E

Drug: Treatment F

Drug: Treatment D

Part II - Sequence EFD

Experimental group

Description:

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

Treatment:

Drug: Treatment E

Drug: Treatment F

Drug: Treatment D

Part II - Sequence EDF

Experimental group

Description:

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

Treatment:

Drug: Treatment E

Drug: Treatment F

Drug: Treatment D

Part II - Sequence FDE

Experimental group

Description:

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

Treatment:

Drug: Treatment E

Drug: Treatment F

Drug: Treatment D

Part II -Sequence FED

Experimental group

Description:

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

Treatment:

Drug: Treatment E

Drug: Treatment F

Drug: Treatment D