Safety, Tolerability, and Pharmacokinetics of MK-8266 in Elderly Participants With High Blood Pressure (MK-8266-003)
- Registration Number
- NCT01263314
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Panel A MK-8266 0.3 mg (Elderly Males with Mild/Mod. HTN) MK-8266 MK-8266 single dose 0.3 mg Panel A MK-8266 0.6 mg (Elderly Males with Mild/Mod. HTN) MK-8266 MK-8266 single dose 0.6 mg Panel A MK-8266 0.7/0.3 mg (Elderly Males with Mild/Mod. HTN) MK-8266 MK-8266 single dose 0.7 mg and then 0.3 mg after 10 hours Panel B MK-8266 0.7/0.3 mg (Elderly Fem. with Mild/Mod. HTN) MK-8266 MK-8266 single dose 0.7 mg and then 0.3 mg after 10 hours Panel B Placebo to MK-8266 (Elderly Fem. with Mild/Mod. HTN) Placebo Placebo to MK-8266 single dose Panel A Placebo to MK-8266 (Elderly Males with Mild/Mod. HTN) Placebo Placebo to MK-8266 single dose Panel B MK-8266 0.3 mg (Elderly Females with Mild/Mod. HTN) MK-8266 MK-8266 single dose 0.3 mg Panel B MK-8266 0.6 mg (Elderly Females with Mild/Mod. HTN) MK-8266 MK-8266 single dose 0.6 mg
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) Up to 48 days 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.
Number of Participants With Abnormal Laboratory Hematology Values Reported as an AE Up to 48 days 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.
Number of Participants With Abnormal Laboratory Chemistry Values Reported as an AE Up to 48 days 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.
Number of Participants With Abnormal Laboratory Urinalysis Values Reported as an AE Up to 37 days 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.
Change From Baseline in Systolic Blood Pressure (SBP) Baseline and 0 to 8 hours postdose Participants rested for at least 10 minutes prior to having vital sign measurements obtained.
Change From Baseline in Heart Rate Baseline and 0 to 8 hours postdose 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.
Number of Participants With Abnormal Electrocardiograms (ECG) Reported as an AE Up to 48 days 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.
- Secondary Outcome Measures
Name Time Method MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax) Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose. 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.
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. Up to 8 hours post dose in each dosing period (Up to 8 hours) 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.
MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose. 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.
MK-8266 PK Parameter Apparent Half-Life (t1/2) Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose. 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.
MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax) Period 1, 2 and 3: Predose, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours postdose. 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.