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MK-7145

Phase 1

Hypertension | Small molecule | Cardiovascular |Merck & Company, Inc.|Last Updated: Sep 21, 2018

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 Trials1
Total Enrollment46
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01370655A Study of MK-7145 Compared to Placebo and Hydrochlorothiazide for Lowering Blood Pressure in Male Participants With Hypertension (MK-7145-009)PHASE1 COMPLETED 46Jun 15, 2011Jan 26, 2012Sep 21, 2018 -
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Study Endpoints
Primary Endpoints
Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Systolic Blood Pressure (SBP)
Baseline and Day 28

Each participant had their blood pressure monitored by continuous 24-hour ambulatory blood pressure monitoring (ABPM) on Days -1 and 28 of each treatment period. The average systolic blood pressure over the 24-hour monitoring period was calculated for baseline (Day -1) and Day 28. The difference between baseline and Day 28 was calculated and recorded.

Change From Baseline in Time-weighted Average Over 24 Hours Post Dose (TWA [0-24]) in Diastolic Blood Pressure (DBP)
Baseline and Day 28

Each participant had their blood pressure monitored by continuous 24-hour ambulatory blood pressure monitoring (ABPM) on Days -1 and 28 of each treatment period. The average diastolic blood pressure over the 24-hour monitoring period was calculated for baseline (Day -1) and Day 28. The difference between baseline and Day 28 was calculated and recorded.

Change From Baseline in Urine Sodium at 24 Hours Post-dose on Day 1
Baseline (Day-1) and Day 1

Urine sodium (Na) levels were measured over 24-hours on Day -1 (baseline) and on Day 1. The total amount of Na excreted in the urine for Day-1 (baseline) and Day1 were calculated and the difference between the 2 values was recorded.

Percentage of Participants Who Experienced at Least 1 Adverse Event (AE)
Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced an AE during the study was summarized by study drug taken at the time of the AE.

Percentage of Participants Who Had Study Discontinued During the Study Due to an Adverse Event (AE)
up to 4 weeks of each treatment period

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who had the administration of the study drug discontinued during the study was summarized by study drug taken at the time of the AE. Participants may or may not have completed the study.

Percentage of Participants Who Experienced at Least 1 Drug-related Adverse Event (AE)
Up to 14 days post last dose of each treatment period (total of 6 weeks for each treatment period)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an AE. The percentage of participants who experienced an AE that was reported as at least possibly-related to the study was summarized by study drug taken at the time of the AE.

Secondary Endpoints
Change From Baseline in Urine Potassium at 24 Hours Post-dose on Day 28
Baseline (Day -1) and Day 28
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelCROSSOVER
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
MK-7145 6 mg (Treatment A)EXPERIMENTALMK-7145 3 mg (three x 1-mg MK-7145 capsules administered orally) and placebo to HCTZ (two 12.5-mg capsules) then three x 1-mg MK-7145 capsules 4 hours later, daily for 4 weeks.
MK-7145 3 mg (Treatment B)EXPERIMENTALMK-7145 3 mg (one 2mg MK-7145 and one MK-7145 placebo capsule) then one 1-mg MK-7145 capsule and two MK-7145 placebo capsules 4 hours later and placebo to HCTZ (2 capsules once daily) daily for 4 weeks.
Hydrochlorothiazide 25 mg (Treatment C)ACTIVE_COMPARATORHCTZ 25 mg (two 12.5-mg capsules) and placebo to MK-7145 (one 3-mg capsule) then placebo for MK-7145 (one 3-mg capsule) 4 hours later daily for 4 weeks.
Placebo (Treatment D)PLACEBO_COMPARATORPlacebo to MK-7145 (2 x 3-mg capsules) and placebo to HCTZ 25 mg (2 capsules) then placebo to MK-7145 (2 x 3-mg capsules) 4 hours later daily for 4 weeks
Interventions
NameTypeDescription
MK-7145DRUG -
Hydrochlorothiazide (HCTZ)DRUG -
Placebo to MK-7145DRUG -
Placebo to HCTZDRUG -
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Eligibility Criteria
Age Range18 Years — 75 Years
SexMALE
Healthy VolunteersNo

Inclusion criteria: * Diagnosis of essential hypertension * Body mass index (BMI) ≤35 kg/m\^2 * Participant in general good health * No history of clinically significant arrhythmias or clinically significant abnormality on electrocardiogram (ECG) * No history of clinically significant cardiac disea...

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