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MK-3328

Phase 1

Alzheimer's Disease | Small molecule | Neurology |Merck & Company, Inc.|Last Updated: Nov 3, 2015

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 Enrollment19
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00954538Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001)PHASE1 COMPLETED 19Aug 1, 2009May 1, 2011Nov 3, 2015 -
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Study Endpoints
Primary Endpoints
Number of Participants With an Adverse Event (AE)
Up to 14 days after last dose

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.

Number of Participants Who Discontinued Study Due to an AE
Up to 14 days after last dose

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.

Effective Dose of [18F]MK-3328
Up to approximately 6 hours post dose

Using PET whole body images acquired after dosing, regions of interest (ROIs) were drawn in all organs showing visible \[18F\]MK-3328 accumulation. Time activity curves (TACs) showing total \[18F\]MK-3328 retention as a function of time were determined for each organ. Residence times were calculated from the area under each organ TAC. Radiation exposure of the body and critical organs was calculated from the \[18F\]MK-3328 residence times using OLINDA (Organ Level Internal Dose Assessment) software. For each organ, the equivalent dose, which is the absorbed radiation dose weighted for the degree of the biological effect of different types of radiation, was calculated. The total radiation exposure to the body is expressed as the effective dose, which is the sum of the equivalent doses in each organ multiplied by a weighting factor for the type of tissue exposed. Effective dose is the primary surrogate for radiation risk. The unit of effective dose is the Sievert (Sv).

Organ Effective Dose of [18F]MK-3328
Up to approximately 6 hours post dose

Using PET whole body images acquired after dosing, ROIs were drawn in all organs showing visible \[18F\]MK-3328 accumulation. TACs showing total \[18F\]MK-3328 retention as a function of time were determined for each organ. Residence times were calculated from the area under each organ TAC. Radiation exposure of the body and critical organs was calculated from the \[18F\]MK-3328 residence times using OLINDA software. For each organ, the equivalent dose, which is the absorbed radiation dose weighted for the degree of the biological effect of different types of radiation, was calculated. The organ effective dose is the equivalent dose in each organ multiplied by a weighting factor for the type of tissue exposed. The unit of organ effective dose is Sv.

Mean Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) in AD Participants and HE Participants
60-90 minutes post dose

Using PET brain images acquired after dosing, regions of interest (ROIs) were drawn in identified brain areas. The ROIs were projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue TACs. SUVR is calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum. Cortical SUVR is reported, which is a mean SUVR derived from SUVR from multiple brain regions (frontal cortex, parietal cortex, anterior cingulate gyrus, posterior cingulate gyrus, temporal cortex, lateral temporal cortex and occipital cortices).

Least Squares (LS) Mean [18F]MK-3328 SUVR in Brain Posterior Cingulate Gyrus in AD Participants and HE Participants
60-90 minutes after second dose

Using PET brain images acquired after the second dose of \[18F\]MK-3328, regions of interest (ROIs) were drawn in identified brain areas. The ROIs were projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue TACs. Posterior cingulate gyrus SUVR was calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum.

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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeDIAGNOSTIC
Treatment Arms
ArmTypeDescription
Part I, Healthy ParticipantsEXPERIMENTALHealthy participants will receive a single intravenous (IV) dose of \~150 megabecquerel (MBq) \[18F\]MK-3328 in Part I of the study
Part II, HE and AD ParticipantsEXPERIMENTALHE and AD participants will receive a single IV dose of \~150 megabecquerel (MBq) \[18F\]MK-3328 in Part II of the study
Part III, HE and AD ParticipantsEXPERIMENTALHE and AD participants will receive two separate IV doses of \~150 megabecquerel (MBq) \[18F\]MK-3328 in Part III of the study
Interventions
NameTypeDescription
[18F]MK-3328DRUGIV dose of \~150 megabecquerel (MBq) \[18F\]MK-3328
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Eligibility Criteria
Age Range50 Years — N/A
SexALL
Healthy VolunteersYes

Inclusion Criteria: Part I: * Participant is male or female of non-reproductive potential between 50 and 65 years old. * Participant is less than 6'5" tall * Participant is in good health * Participant has been a non-smoker for at least 10 years Parts II and III: * Male or female of non-reproduc...

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