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MK-8892

Phase 1

Pulmonary Arterial Hypertension | Small molecule | Cardiovascular |Merck & Company, Inc.|Last Updated: Jul 22, 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-BlindCONTROLLEDBiomarker
Total Trials2
Total Enrollment48
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01926509Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-005)PHASE1 COMPLETED 23Nov 14, 2013Sep 8, 2014Dec 3, 2018 -
NCT01798849A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)PHASE1 COMPLETED 25Mar 15, 2013Jul 17, 2013Jul 22, 2019 -
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Study Endpoints
Primary Endpoints
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 at Day 1 and Day 28
Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 28

Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose on Days 1 and 28 to determine the AUC0-24hr.

Number of Participants Who Experienced an Adverse Event (AE)
Up to 42 days

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants that reported at least 1 AE was summarized.

Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event
Up to 28 days

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants who had study drug discontinued due to an AE was summarized.

Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants
up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.

Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants
up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.

Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants
Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants
up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.

Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants
up to 7 weeks

An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.

Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants
Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)

Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

Secondary Endpoints
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants
Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants
Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants
Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
MK-8892 Panel AEXPERIMENTALParticipants will be administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28).
MK-8892 Panel BEXPERIMENTALParticipants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28).
MK-8892 Panel CEXPERIMENTALParticipants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28).
Placebo (Panels A and B)PLACEBO_COMPARATORParticipants will be administered placebo to MK-8892 once daily for 28 days.
Panel A-HealthyEXPERIMENTALWithin each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, 14 mg or 2.0 mg fed, and 2 participants received placebo. Dosing periods will alternate with Panel B.
Panel B-HealthyEXPERIMENTALWithin each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods will alternate with Panel A.
Panel C-Mild/Moderate HypertensionEXPERIMENTALWithin each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages will be determined by the results of Panels A and B.
Interventions
NameTypeDescription
MK-8892DRUG -
Placebo for MK-8892DRUG -
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Eligibility Criteria
Age Range18 Years — 70 Years
SexALL
Healthy VolunteersNo

Inclusion Criteria: * If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered * B...

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