A Single Dose Study of MK-8266 (MK-8266-001)
15 oktober 2018 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
25
Fas
- Fas 1
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 55 år (Vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Manlig
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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.
|
|
Experimentell: 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.
Andra namn:
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-jämförare: 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.
Andra namn:
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.
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Number of Participants Who Experienced One or More Adverse Events
Tidsram: 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
Tidsram: 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
Tidsram: 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])
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
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
Tidsram: 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
Tidsram: 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)
Tidsram: 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
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
18 november 2009
Primärt slutförande (Faktisk)
14 maj 2010
Avslutad studie (Faktisk)
14 maj 2010
Studieregistreringsdatum
Först inskickad
3 december 2009
Först inskickad som uppfyllde QC-kriterierna
3 december 2009
Första postat (Uppskatta)
4 december 2009
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
20 februari 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
15 oktober 2018
Senast verifierad
1 oktober 2018
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 8266-001
- MK-8266-001 (Annan identifierare: Merck protocol number)
- 2009_700 (Annan identifierare: Telerx ID)
- 2009-015774-36 (EudraCT-nummer)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Ja
IPD-planbeskrivning
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
produkt tillverkad i och exporterad från U.S.A.
Nej
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .