A Multiple Dose Study of MK-3614 (MK-3614-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: MK-3614; Drug: Placebo for MK-3614

Study type: Interventional

Funder types: Industry

Identifiers

NCT01033643

3614-002

2009-010401-36 (EudraCT Number)

2009_704 (Other Identifier)

MK-3614-002 (Other Identifier)

Details and patient eligibility

About

This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of MK-3614 in male participants with mild to moderate hypertension. The primary hypotheses are: 1) Multiple oral doses of MK-3614 are sufficiently safe and well tolerated to permit continued clinical investigation 2) Aortic Augmentation Index (Aix) is reduced 24 hours post the last dose of MK-3614 administered compared to placebo and 3) Increase in the 12-hour weighted averages (TWA 0-12hours) of the heart rate is within 15 beats per minute (bpm) of baseline on first day of multiple dosing of MK-3614 and within 10 bpm of baseline on last day of multiple dosing of MK-3614.

Enrollment: 30 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has mild to moderate hypertension
• Has grade 1 or 2 arterial hypertension being treated with a single antihypertensive drug
• Has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months; or who have discontinued smoking or the use of nicotine/nicotine-containing products for at least approximately 3 months
• Is in generally good health

Exclusion criteria

• Has a history of clinically significant abnormalities or diseases
• Has a history of stroke, chronic seizures, or major neurological disorder
• Has a functional disability that can interfere with rising from a sitting position to the standing position
• Has any personal or family history of a bleeding or a clotting disorder
• Has a history of frequent nose bleeds or has recurrent or active gingivitis
• Has a history of cancer
• Has a history of clinically significant cardiac disease
• Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies approximately 2 weeks prior to the administration of study drug
• Consumes excessive amounts of alcohol
• Consumes excessive amounts of caffeinated beverages per day
• Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks of study
• Has a history of significant multiple and/or severe allergies (including latex) to prescription or non-prescription drugs or food
• Is currently a regular user of any illicit drugs or has a history of drug abuse within approximately 1 year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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30 participants in 6 patient groups, including a placebo group

MK-3614 0.25 mg (Panel A)

Experimental group

Description:

Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.

Treatment:

Drug: MK-3614

MK-3614 0.50/0.25 mg (Panel B)

Experimental group

Description:

Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM) 12 hours apart orally for 10 days.

Treatment:

Drug: MK-3614

MK-3614 0.50/0.25 mg (Panel C Repeat)

Experimental group

Description:

Participants were to receive 0.75 mg of MK-3614 BID every 12 hours orally for 10 Days. Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.

Treatment:

Drug: MK-3614

MK-3614 0.50 mg (Panel D)

Experimental group

Description:

Participants received 0.50 mg of MK-3614 three times a day (TID) orally every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and 0.50 mg of MK-3614 every 12 hours orally for 10 days (Days 4-13).

Treatment:

Drug: MK-3614

MK-3614 0.50 mg (Panel E)

Experimental group

Description:

Participants were to receive orally 0.50 mg of MK-3614 BID every 12 hours on Day 1 followed by 3 doses (0.50/0.50/0.25 mg) of MK-3614 each 8 hours apart on Day 2; three doses of 0.50 mg of MK-3614 8 hours apart on Days 3,4; and 0.75 mg of MK-3614 BID every 12 hours on Days 5-14. No participants were enrolled in this group.

Treatment:

Drug: MK-3614

Placebo (All Panels)

Placebo Comparator group

Description:

Participants received a dose matched placebo orally according to randomization.

Treatment:

Drug: Placebo for MK-3614