A Single Dose Study of MK-8266 (MK-8266-001)
15 октября 2018 г. обновлено: Merck Sharp & Dohme LLC
A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266
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.
Обзор исследования
Статус
Завершенный
Условия
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Интервенционный
Регистрация (Действительный)
25
Фаза
- Фаза 1
Критерии участия
Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.
Критерии приемлемости
Возраст, подходящий для обучения
От 18 лет до 55 лет (Взрослый)
Принимает здоровых добровольцев
Нет
Полы, имеющие право на обучение
Мужской
Описание
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
Учебный план
В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Одногрупповое задание
- Маскировка: Двойной
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Panel A, Healthy Male Participants, Sequence 1
MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: placebo/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel A, Healthy Male Participants, Sequence 2
MK-8266 in Period 1: 0.1 mg/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: placebo/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel A, Healthy Male Participants, Sequence 3
MK-8266 in Period 1: 0.1 mg/ Period 2: placebo/ Period 3: 0.5/ Period 4: 1.0 mg/ Period 5: placebo.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel A, Healthy Male Participants, Sequence 4
MK-8266 in Period 1: placebo/ Period 2: 0.2 mg/ Period 3: 0.5 mg/ Period 4: 1.0 mg/ Period 5: 1.0 mg dose followed in 6 hours by a 0.8 mg dose.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel B, Healthy Male Participants, Sequence 1
MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: placebo/ Period 4: 0.4 mg fed/ Period 5: na.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel B, Healthy Male Participants, Sequence 2
MK-8266 in Period 1: 0.4 mg/ Period 2: placebo/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel B, Healthy Male Participants, Sequence 3
MK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 0.4 mg fed/ Period 5: na.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel B, Healthy Male Participants, Sequence 4
MK-8266 in Period 1: placebo/ Period 2: 1.2 mg/ Period 3: 1.2 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na.
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel C, Mild/Moderate Hypertension, Sequence 1
Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel C, Mild/Moderate Hypertension, Sequence 2
Period 1: placebo/ Period 2 1.2 mg dose followed in 8 hours by a 1.0 mg dose/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel C, Mild/Moderate Hypertension, Sequence 3
Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2 placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel C, Mild/Moderate Hypertension, Sequence 4
Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: placebo/ Period 3: 1.0 mg dose followed in 6 hours by a 0.6 mg dose followed in 6 hours by a 0.6 mg dose/ Period 4: placebo/ Period 5: na
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Экспериментальный: Panel C, Mild/Moderate Hypertension, Sequence 5
Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: 1.0 mg dose followed in 6 hours by a 1.0 mg dose followed in 6 hours by a 0.6 mg dose/ Period 5: na
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
|
Плацебо Компаратор: Panel C, Mild/Moderate Hypertension, Sequence 6
Period 1: 1.0 mg dose followed in 8 hours by a 0.8 mg dose/ Period 2: 1.2 mg dose followed in 8 hours by a 1.0 mg dose// Period 3: placebo/ Period 4: placebo/ Period 5: na
|
Single oral doses of 0.1 to 1.2 mg of MK-8266 in 0.1 capsule form.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Some participants will receive study drug with food.
Другие имена:
MK-8266 1.0 mg oral capsule.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
Placebo to match MK-8266 0.1 or 1.0 mg.
Participants will fast for 8 hours prior to dosing.
There will be at least a 7- day washout period between doses for any given participant.
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Number of Participants Who Experienced One or More Adverse Events
Временное ограничение: Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days)
|
An adverse event (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.
Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.
|
Up to 14 days after administration of last dose of study drug in each study period (Up to 43 Days)
|
|
Number of Participants Who Discontinued Study Drug Due to an AE
Временное ограничение: Up to 43 days
|
An adverse event (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.
Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.
|
Up to 43 days
|
|
Aortic Augmentation Index - Time-Weighted Average 0-24 Hours
Временное ограничение: Predose, 1.5, 3, 12, and 24 hours postdose
|
Central ascending aortic blood pressure augmentation index (AIx) is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness.
AIx can be measured non-invasively by radial tonometry using aplanation tonometry of radial artery with the SphygmoCor Pulse Wave Analysis System Guide (SphygmoCor system).
AIx was performed at prestudy to ensure an adequate waveform can be obtained.
At each time point, a minimum of 2 AIx were completed in an attempt to obtain 2 acceptable quality assessments.
A time weighted average was calculated.
AIx was adjusted for heart rate.
A decrease in the AIx of ≥5 percentage is considered clinically meaningful.
Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.
The 12-hour measurement was not collected (per protocol) in all periods of Panels A and B.
|
Predose, 1.5, 3, 12, and 24 hours postdose
|
|
MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
Временное ограничение: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 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.
AUC[0-inf] was not collected, analyzed or summarized for participants receiving placebo.
|
Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
|
|
MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax)
Временное ограничение: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 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.
For Panel A 1.0/0.8
mg MK-8266, the second dose was not well characterized due to limited sampling.
Observed exposure likely underestimates the true exposure.
Cmax was not collected, analyzed or summarized for participants receiving placebo.
|
Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
|
|
MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax)
Временное ограничение: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 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.
Tmax was not collected, analyzed or summarized for participants receiving placebo.
|
Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
|
|
MK-8266 PK Parameter Apparent t1/2
Временное ограничение: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 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%.
Harmonic means +/- Pseudo standard deviations are displayed.
t1/2 was not collected, analyzed or summarized for participants receiving placebo.
|
Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
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
Временное ограничение: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose
|
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body.
AUC[0-24 hours] is a measure of the mean concentration levels of drug in the plasma after the dose.
The Fed Group was administered a high fat meal.
|
Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 postdose
|
|
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
Временное ограничение: Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 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.
The Fed Group was administered a high fat meal.
|
Predose, 0.5, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 hours postdose
|
|
Time-Weighted Average of Heart Rate (0-12 Hours)
Временное ограничение: Up to 12 hours
|
HR was measured with a validated automatic measuring device.
Time weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period.
The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.
Participants in Arms/Groups in which MK-8266 or placebo was administered in more than one period were counted separately for each period.
|
Up to 12 hours
|
Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Даты записи исследования
Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.
Изучение основных дат
Начало исследования (Действительный)
18 ноября 2009 г.
Первичное завершение (Действительный)
14 мая 2010 г.
Завершение исследования (Действительный)
14 мая 2010 г.
Даты регистрации исследования
Первый отправленный
3 декабря 2009 г.
Впервые представлено, что соответствует критериям контроля качества
3 декабря 2009 г.
Первый опубликованный (Оценивать)
4 декабря 2009 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
20 февраля 2019 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
15 октября 2018 г.
Последняя проверка
1 октября 2018 г.
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- 8266-001
- MK-8266-001 (Другой идентификатор: Merck protocol number)
- 2009_700 (Другой идентификатор: Telerx ID)
- 2009-015774-36 (Номер EudraCT)
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Да
Описание плана IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Нет
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Нет
продукт, произведенный в США и экспортированный из США.
Нет
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .