A Single Dose Study of MK-8266 (MK-8266-001)
2018년 10월 15일 업데이트: 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.
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (실제)
25
단계
- 1단계
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
남성
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 단일 그룹 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
실험적: 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.
다른 이름들:
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.
|
|
위약 비교기: 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.
다른 이름들:
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.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of Participants Who Experienced One or More Adverse Events
기간: 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
기간: 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
기간: 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])
기간: 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)
기간: 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)
기간: 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
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
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
기간: 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
기간: 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)
기간: 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
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2009년 11월 18일
기본 완료 (실제)
2010년 5월 14일
연구 완료 (실제)
2010년 5월 14일
연구 등록 날짜
최초 제출
2009년 12월 3일
QC 기준을 충족하는 최초 제출
2009년 12월 3일
처음 게시됨 (추정)
2009년 12월 4일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 2월 20일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 10월 15일
마지막으로 확인됨
2018년 10월 1일
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- 8266-001
- MK-8266-001 (기타 식별자: Merck protocol number)
- 2009_700 (기타 식별자: Telerx ID)
- 2009-015774-36 (EudraCT 번호)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
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아니
미국에서 제조되어 미국에서 수출되는 제품
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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