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MK-6240, ~185 MBq

Phase 1

Alzheimer's Disease | Small molecule | Neurology |Merck & Company, Inc.|Last Updated: Sep 18, 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
CONTROLLEDBiomarker
Total Trials1
Total Enrollment13
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02562989[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)PHASE1 COMPLETED 13Oct 19, 2015Dec 27, 2016Sep 18, 2018 -
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Study Endpoints
Primary Endpoints
Number of Participants With Adverse Events (AEs)
Part 1: Up to 5 weeks; Part 2: up to 16 weeks

The number of participants experiencing an adverse event (AE) was monitored. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.

Number of Participants Who Discontinued Study Due to an AE
Part 1: Up to 5 weeks; Part 2: up to 16 weeks

The number of participants discontinuing study due to an AE was monitored.

Effective Dose of [18F]MK-6240
Up to approximately 5 hours following [18F]MK-6240 administration

Mean effective dose (ED) of \[18F\]MK-6240 was calculated from whole-body (WB) PET scans of healthy young participants included in Part 1 of study. ED, reported as microsieverts (µSv) / megabecquerel (MBq), is a measure of WB radiation exposure risk that accounts for differences in individual organ exposure and organ susceptibility to ionizing radiation. Following \[18F\]MK-6240 PET tracer administration, organ-specific time-activity curves (TACs) and radioactivity residence times were utilized to calculate exposure risk for individual organs. These values calculated for individual organs were then entered into a human biodistribution model to determine ED of \[18F\]MK-6240.

Organ Effective Dose of [18F]MK-6240
Up to approximately 5 hours following [18F]MK-6240 administration

Mean organ ED of \[18F\]MK-6240 was calculated from WB PET scans of healthy young participants included in Part 1 of study. Organ ED, reported as micrograys (µGy) / MBq, is a measure of organ-specific radiation exposure risk. Following \[18F\]MK-6240 PET tracer administration, organ-specific TACs and radioactivity residence times were utilized to calculate organ ED for specific organs of the body.

Standardized Uptake Value Ratio (SUVR) of [18F]MK-6240 in Brain Regions of Interest
From 60 to 90 minutes following [18F]MK-6240 administration

As a surrogate of regional \[18F\[MK-6240 tracer distribution volume (VT), mean standardized uptake value ratios (SUVRs), were calculated for specific brain regions of interest (ROIs) in healthy elderly as well as AD/MCI elderly participants in Part 2 of the study. Calculated using calibrated PET scan images from each participant, SUVR is the relative ratio of pixel intensities at a specific brain ROI compared to a reference region (RR; cerebellar cortex, for this study). For an individual participant, the average SUVR for each brain ROI is calculated starting at 60 minutes and ending at 90 minutes following \[18F\]MK-6240 administration to quantify tracer retention; referred to as "SUVR (60-90min)." An SUVR (60-90 min) \< 1 indicates decreased tracer retention at brain ROI relative to RR. An SUVR (60-90 min) = 1 indicates no difference in tracer retention at brain ROI relative to RR. An SUVR (60-90 min) \> 1 indicates increased tracer retention at brain ROI relative to RR.

Intra-subject Test-Retest (T-RT) Variability of Standardized Uptake Value Ratio (SUVR) in Brain Regions of Interest
Up to 16 weeks following initial dose of [18F]MK-6240

For each AD/MCI participant receiving 2 doses of MK-6240, the SUVR (60-90 min) during initial dose (SUVR\_1) was compared to the SUVR (60-90 min) during the second dose (SUVR\_2) to determine the percent test-retest (T-RT) variability of the SUVR (60-90 min) for each brain ROI. T-RT variability = (absolute value (SUVR\_1 - SUVR\_2) / average SUVR) \* 100. If T-RT variability = 0, indicates no variability between SUVR\_1 and SUVR\_2.

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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeDIAGNOSTIC
Treatment Arms
ArmTypeDescription
Part 1, Healthy Young ParticipantsEXPERIMENTALHealthy young participants received a single intravenous (IV) dose of \~185 megabecquerel (MBq) \[18F\]MK-6240 in Part 1 of the study
Part 2, Healthy Elderly ParticipantsEXPERIMENTALHealthy elderly participants received a single IV dose of \~160 MBq \[18F\]MK-6240, in Part 2 of the study
Part 2, AD and Amnestic MCI Elderly ParticipantsEXPERIMENTALAD and amnestic MCI participants received up to two IV doses of \~160 MBq \[18F\]MK-6240 in Part 2 of the study
Interventions
NameTypeDescription
[18F]MK-6240, ~185 MBqDRUGIV dose of \~185 MBq \[18F\]MK-6240
[18F]MK-6240, ~160 MBqDRUGIV dose of \~160 MBq \[18F\]MK-6240
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Eligibility Criteria
Age Range18 Years — 85 Years
SexALL
Healthy VolunteersYes

Inclusion Criteria: Part 1 and Part 2: * Male, or non-pregnant and non-breast feeding female; in addition: * Male participant who is sexually active with females of childbearing potential must be willing to use a condom from the first dose of study drug until 3 months post the last dose of stud...

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