A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK8266 in Hypertensive Men (MK-8266-002)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: Placebo TID (Panel C); Drug: Placebo BID (Panel B); Drug: Placebo TID (Panel D); Drug: MK-8266 TID, 1.8 mg; Drug: MK-8226 BID, 1 mg; Drug: Placebo TID (Panel E); Drug: MK-8266 BID, 1.8 mg; Drug: Placebo BID (Panel A); Drug: MK-8266 TID, 2.4 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01096160

2010-018654-13 (EudraCT Number)

8266-002

Details and patient eligibility

About

This study evaluated adverse events (AEs), study discontinuation due to AEs, and pharmacodynamics of MK-8266 in male participants with mild to moderate hypertension.

Full description

This study evaluated AEs, discontinuation due to AEs, and effects on hemodynamic parameters, including systolic blood pressure (SBP) and aortic augmentation index (AIx), following multiple oral doses of MK-8266. Five serial panels, each consisting of eight participants (40 participants in Panels A, B, C, D, and E), were randomized to receive either MK-8266 or matching placebo twice daily (BID) or three times daily (TID) for 10 consecutive days. Although the original plan was to evaluate MK-8266 treatment in Panels D and E using both BID and TID regimens, the study actually evaluated identical TID regimens in these panels.

Enrollment: 40 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant is male with essential hypertension (high blood pressure)
• Participant is in good general health (with the exception of hypertension)
• Participant has a Body Mass Index (BMI) <= 33 kg/m^2 at the Screening visit
• Participant has a platelet count >= 150,000 cu/mL at the Screening visit
• Participant has a positive AIx at the Screening visit

Exclusion criteria

• Participant has a history of stroke, chronic seizure, or major neurological disease
• Participant has a functional disability that can interfere with rising from a seated position to the standing position
• Participant has any history of a bleeding or clotting disorder
• Participant has a history of cancer
• Participant is unable to refrain from or anticipates the use of any prescription or non-prescription medication
• Participant consumes excessive amounts of alcohol or caffeinated beverages daily

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

---

40 participants in 5 patient groups

Panel A: MK-8266 BID, 1 mg/Placebo

Experimental group

Description:

MK-8266 1 mg (0.7 mg in the morning \[AM\] + 0.3 mg in the evening \[PM\]), or as matching placebo BID.

Treatment:

Drug: Placebo BID (Panel A)

Drug: MK-8226 BID, 1 mg

Panel B: MK-8266 BID, 1.8 mg/Placebo

Experimental group

Description:

MK-8266 1.8 mg (1 mg in the AM + 0.8 mg in the PM), or as matching placebo BID.

Treatment:

Drug: MK-8266 BID, 1.8 mg

Drug: Placebo BID (Panel B)

Panel C: MK-8266 TID, 1.8 mg/Placebo

Experimental group

Description:

MK-8266 TID, 1.8 mg (0.6 mg every 6 hours \[q6hr\]), or as matching placebo TID.

Treatment:

Drug: Placebo TID (Panel C)

Drug: MK-8266 TID, 1.8 mg

Panel D: MK-8266 TID, 2.4 mg/Placebo

Experimental group

Description:

MK-8266 TID (Panel D), 2.4 mg (0.8 mg q6hr), or as matching placebo TID. Panel D was completed prior to initiation of Panel E.

Treatment:

Drug: MK-8266 TID, 2.4 mg

Drug: Placebo TID (Panel D)

Drug: MK-8266 TID, 2.4 mg

Panel E: MK-8266 TID, 2.4 mg/Placebo

Experimental group

Description:

MK-8266 TID (Panel E), 2.4 mg (0.8 mg q6hr), or as matching placebo TID. Panel E was initiated after completion of Panel D.

Treatment:

Drug: Placebo TID (Panel E)

Drug: MK-8266 TID, 2.4 mg

Drug: MK-8266 TID, 2.4 mg