This is a randomized, double-blind, placebo-controlled study. The hypothesis for this study is that single oral doses of MK-8266 selected for this study are sufficiently safe and well tolerated by elderly male and elderly female participants with hypertension to permit continued clinical investigation.
Two panels, each consisting of eight participants (8 elderly males with mild to moderate hypertension in Panel A and 8 elderly females with mild to moderate hypertension in Panel B) will be randomized to receive either MK-8266 or matching placebo in a 3:1 ratio. Participants will receive single doses of MK-8266 or matching placebo in three treatment periods (Periods 1 through 3). In both Panel A and Panel B, doses will escalate in a rising, fixed sequence. In Period 1 (0.3 mg), Period 2 (0.6 mg), and Period 3 (0.7 mg and then 0.3 mg 10 hours later) once daily doses of MK-8266 or matching placebo will be administered. All participants will receive at least 2 doses of MK-8266. Participants completing placebo treatment in Period 1 will flow to the MK-8266 arm in the next period, with 2 participants from the MK-8266 arm receiving placebo in the next period. Blood samples will be obtained pre-dose and at selected time points up to 48 hours post-dose for determination of MK-8266 plasma concentrations.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
16
Number of Participants With Adverse Events (AEs)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to 48 days
Number of Participants With Abnormal Laboratory Hematology Values Reported as an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Abnormal laboratory hematology value was any AE reported under the System Organ Class of Investigations that was related to an abnormal laboratory hematology value.
Time frame: Up to 48 days
Number of Participants With Abnormal Laboratory Chemistry Values Reported as an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Abnormal laboratory chemistry value was any AE reported under the System Organ Class of Investigations that was related to an abnormal laboratory chemistry value.
Time frame: Up to 48 days
Number of Participants With Abnormal Laboratory Urinalysis Values Reported as an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Abnormal laboratory urinalysis value was any AE reported under the System Organ Class of Investigations that was related to an abnormal laboratory urinalysis value.
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Time frame: Up to 37 days
Change From Baseline in Systolic Blood Pressure (SBP)
Participants rested for at least 10 minutes prior to having vital sign measurements obtained.
Time frame: Baseline and 0 to 8 hours postdose
Change From Baseline in Heart Rate
Participants rested for at least 10 minutes prior to having vital sign measurements obtained. Heart rate measurements were obtained in the semirecumbent position and 3 sets of measurements were obtained approximately 1 minute apart.
Time frame: Baseline and 0 to 8 hours postdose
Number of Participants With Abnormal Electrocardiograms (ECG) Reported as an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. An abnormal ECG value was any AE reported under the System Organ Classes of Investigations or Cardiac that was related to an abnormal ECG value.
Time frame: Up to 48 days
MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. (AUC\[0-inf\]) is a measure of the mean concentration levels of drug in the plasma after the dose.
Time frame: Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose.
MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose.
MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Nominal instead of actual times are presented.
Time frame: Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose.
MK-8266 PK Parameter Apparent Half-Life (t1/2)
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. t1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. Results are presented for the Harmonic Mean ± Pseudo standard deviation.
Time frame: Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose.
The Time Weighted Average Systolic Blood Pressure (SBP) Evaluated Over 8 Hours Post Dose (TWA[0-8hrs]) Following a Single Oral Dose of MK-8266.
Participants rested for at least 10 minutes prior to having vital sign measurements obtained. Single dose effects on central SBP were estimated as a time-weighted average over the 8-hour post single dose observation period.
Time frame: Up to 8 hours post dose in each dosing period (Up to 8 hours)