Clinical trial NCT01096160: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK8266 in Hypertensive Men (MK-8266-002)
Official title: A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Keywords: Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-03-30
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Participants Receiving MK-8266 or Placebo Who Experienced At Least One Adverse Event (AE) During Treatment and Postdose Follow-up
timeFrame: Up to 24 days
measure: Participants Receiving MK-8266 or Placebo Who Discontinued Treatment Due to an AE
timeFrame: Up to 10 days
measure: Change From Baseline in Systolic Blood Pressure (SBP) Following Multiple Oral Doses of MK-8266 or Placebo
timeFrame: Baseline and Day 10
measure: Heart Rate (HR) on Day 10 Following Multiple Oral Doses of MK-8266 or Placebo
timeFrame: Day 10 (24 hours postdose)
Secondary outcomes:
measure: Aortic Augmentation Index (AIx) on Day 10 Following Multiple Oral Doses of MK-8266 or Placebo
timeFrame: Day 10
measure: Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) Following Multiple Oral Doses of MK-8266 or Placebo
timeFrame: Baseline and Day 10
measure: Percent Inhibition of Platelet Aggregation Induced by Adenosine Diphosphate (ADP) Following Multiple Oral Doses of MK-8266 or Placebo
timeFrame: Baseline and Day 10 (5 hours postdose)
measure: Percent Inhibition of Platelet Aggregation Induced by Collagen Following Multiple Oral Doses of MK-8266 or Placebo
timeFrame: Baseline and Day 10 (5 hours postdose)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: