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MK-8266

Phase 1

Hypertension | Small molecule | Cardiovascular |Merck & Company, Inc.|Last Updated: Feb 20, 2019

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDBiomarker
Total Trials2
Total Enrollment41
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01263314Safety, Tolerability, and Pharmacokinetics of MK-8266 in Elderly Participants With High Blood Pressure (MK-8266-003)PHASE1 COMPLETED 16Nov 1, 2010Mar 1, 2011Nov 5, 2018 -
NCT01025791A Single Dose Study of MK-8266 (MK-8266-001)PHASE1 COMPLETED 25Nov 18, 2009May 14, 2010Feb 20, 2019 -
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Study Endpoints
Primary Endpoints
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.

Number of Participants Who Experienced One or More Adverse Events
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.

Number of Participants Who Discontinued Study Drug Due to an AE
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.

Aortic Augmentation Index - Time-Weighted Average 0-24 Hours
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.

MK-8266 Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
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.

MK-8266 PK Parameter Observed Maximum (Peak) Plasma Concentration (Cmax)
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.

MK-8266 PK Parameter Observed Time to Reach Cmax (Tmax)
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.

MK-8266 PK Parameter Apparent t1/2
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.

Secondary Endpoints
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.
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.
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.
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Panel A MK-8266 0.3 mg (Elderly Males with Mild/Mod. HTN)EXPERIMENTALMK-8266 single dose 0.3 mg
Panel A MK-8266 0.6 mg (Elderly Males with Mild/Mod. HTN)EXPERIMENTALMK-8266 single dose 0.6 mg
Panel A MK-8266 0.7/0.3 mg (Elderly Males with Mild/Mod. HTN)EXPERIMENTALMK-8266 single dose 0.7 mg and then 0.3 mg after 10 hours
Panel A Placebo to MK-8266 (Elderly Males with Mild/Mod. HTN)PLACEBO_COMPARATORPlacebo to MK-8266 single dose
Panel B MK-8266 0.3 mg (Elderly Females with Mild/Mod. HTN)EXPERIMENTALMK-8266 single dose 0.3 mg
Panel B MK-8266 0.6 mg (Elderly Females with Mild/Mod. HTN)EXPERIMENTALMK-8266 single dose 0.6 mg
Panel B MK-8266 0.7/0.3 mg (Elderly Fem. with Mild/Mod. HTN)EXPERIMENTALMK-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_COMPARATORPlacebo to MK-8266 single dose
Panel A, Healthy Male Participants, Sequence 1EXPERIMENTALMK-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.
Panel A, Healthy Male Participants, Sequence 2EXPERIMENTALMK-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.
Panel A, Healthy Male Participants, Sequence 3EXPERIMENTALMK-8266 in Period 1: 0.1 mg/ Period 2: placebo/ Period 3: 0.5/ Period 4: 1.0 mg/ Period 5: placebo.
Panel A, Healthy Male Participants, Sequence 4EXPERIMENTALMK-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.
Panel B, Healthy Male Participants, Sequence 1EXPERIMENTALMK-8266 in Period 1: 0.4 mg/ Period 2: 1.2 mg/ Period 3: placebo/ Period 4: 0.4 mg fed/ Period 5: na.
Panel B, Healthy Male Participants, Sequence 2EXPERIMENTALMK-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.
Panel B, Healthy Male Participants, Sequence 3EXPERIMENTALMK-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.
Panel B, Healthy Male Participants, Sequence 4EXPERIMENTALMK-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.
Panel C, Mild/Moderate Hypertension, Sequence 1EXPERIMENTALPeriod 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
Panel C, Mild/Moderate Hypertension, Sequence 2EXPERIMENTALPeriod 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
Panel C, Mild/Moderate Hypertension, Sequence 3EXPERIMENTALPeriod 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
Panel C, Mild/Moderate Hypertension, Sequence 4EXPERIMENTALPeriod 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
Panel C, Mild/Moderate Hypertension, Sequence 5EXPERIMENTALPeriod 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
Panel C, Mild/Moderate Hypertension, Sequence 6PLACEBO_COMPARATORPeriod 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
Interventions
NameTypeDescription
MK-8266DRUGOral capsules, 0.1 mg potency
PlaceboDRUGOral placebo capsules to match MK-8266 capsules
MK-8266 0.1 mgDRUGSingle 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.
MK-8266 1.0 mgDRUGMK-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.
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Eligibility Criteria
Age Range65 Years — 80 Years
SexALL
Healthy VolunteersNo

Inclusion criteria: * Participants are male or non-childbearing female. * Participant with essential hypertension (HTN), Grade 1 or 2 (as per European Society of Hypertension \[ESH\]) or isolated mild to moderate systolic HTN. High normal systolic BP ≥130 mmHg will be also allowed. Blood pressures ...

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