Clinical trial NCT01025791: A Single Dose Study of MK-8266 (MK-8266-001)
Official title: A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-12-04
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A three panel study, to determine if MK-8266 given as a single dose is sufficiently safe and well tolerated. Panel A and B will consist of healthy young males and Panel C will consist of subjects with mild to moderate hypertension. The primary hypotheses for the study are that MK-8266 given as single doses is sufficiently safe and well tolerated to permit continued clinical investigation in healthy young male volunteers and male participants with mild-to-moderate hypertension and that in males with mild to moderate hypertension, at a single oral dose of MK-8266 that is sufficiently safe and well-tolerated, postdose mean time-weighted average across 24 hours of aortic augmentation index (TWA0-12hrs AIx) is reduced compared to placebo. A mean decrease of ≥ 5 percentage points is considered clinically meaningful.

Detailed description: Three panels, each consisting of either 8 or 9 participants (8 healthy young males in Panel A and Panel B; and 9 participants with mild to moderate hypertension in Panel C) will be randomized to receive either MK-8266 or matching placebo in either a 6:2 ratio (Panel A and Panel B) or 6:3 ratio (Panel C), respectively, in up to 5 treatment (1 to 5) periods in Panel A and up to 4 treatment (1 to 4) periods in Panel B and Panel C. In all panels, doses will be escalated in a rising, fixed sequence. Some participants took study drug after fasting and some with food.

Eligibility criteria: Inclusion Criteria:

* For Panel A and B Participant is a healthy male between 18 to 45 years of age. For Panel C Participant is a male with essential hypertension between 18 to 55 years of age
* A non-smoker

Exclusion Criteria:

* Has a history of stroke, chronic seizure or major neurological disorder
* Has a disability that can interfere with rising from a sitting position to the standing position
* Has a personal of family history of bleeding or clotting disorders
* Has a history of cancer
* Is unable to refrain from or anticipates the use of any prescription or nonprescription drug during the study
* Consumes excessive amounts of caffeine or alcohol
* Has had major surgery, donated blood or participated in another investigational study in the past 4 weeks

Primary outcomes:
measure: Number of Participants Who Experienced One or More Adverse Events
timeFrame: Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days)
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 43 days
measure: Aortic Augmentation Index - Time-Weighted Average 0-24 Hours
timeFrame: Predose, 1.5, 3, 12, and 24 hours postdose
measure: MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
timeFrame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
measure: MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax)
timeFrame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
measure: MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax)
timeFrame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
measure: MK-8266 PK Parameter Apparent t1/2
timeFrame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
Secondary outcomes:
measure: Effect of Food on MK-8266 PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24hr) Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants
timeFrame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose
measure: Effect of Food on MK-8266 PK Parameter Cmax Following Administration of Single Oral Doses of MK-8266 at 0.4 mg to Healthy Male Participants
timeFrame: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
measure: Time-Weighted Average of Heart Rate (0-12 Hours)
timeFrame: Up to 12 hours
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: