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Completed

NCT Number: NCT00954538

Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001)

This study will estimate the radiochemical and radiation safety and assess the efficacy of [18F]MK-3328, a novel positron emission tomography (PET) tracer. The study safety hypotheses will test whether [18F]MK-3328 is sufficiently safe and well-tolerated, based on an assessment of clinical and laboratory evaluations and adverse experiences in healthy participants, including healthy elderly (HE) participants, and Alzheimer's disease (AD) participants, to permit continued investigation. The study efficacy hypothesis will test whether [18F]MK-3328 can discriminate between AD participants and cognitively normal elderly control participants based on tracer volume of distribution, or one of its surrogates, in brain posterior cingulate gyrus.

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Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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-reproductive potential at least 55 years of age
  • Participant is cognitively normal (HE participants), or has probable mild-to moderate AD (AD participants)
  • Participant is willing to have an arterial catheter placed in the radial artery (Part II only)

Exclusion criteria

Part I:

  • Participant has a history of stroke, seizures, or neurological disorder
  • Participant has or has a history of any disease or condition, or takes any medication that would interfere with assessment of the tracer or make participation unsafe or unduly uncomfortable

Parts II and III:

  • Participant has a history or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with altered cognition
  • Participant has or has a history of any disease or condition, or takes any medication that would interfere with assessment of the tracer or make participation unsafe or unduly uncomfortable
  • Participant is living in a nursing home or skilled nursing facility

Treatment and study plan

[18F]MK-3328

Drug

IV dose of ~150 megabecquerel (MBq) [18F]MK-3328

Primary outcomes

  1. Number of Participants With an Adverse Event (AE)

    Time frame: 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.

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

    Time frame: 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.

  3. Effective Dose of [18F]MK-3328

    Time frame: 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).

  4. Organ Effective Dose of [18F]MK-3328

    Time frame: 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.

  5. Mean Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) in AD Participants and HE Participants

    Time frame: 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).

  6. Least Squares (LS) Mean [18F]MK-3328 SUVR in Brain Posterior Cingulate Gyrus in AD Participants and HE Participants

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Three Part Study to Evaluate the Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK-3328, a Radiotracer for Use in Positron Emission Tomography

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Aug 7, 2009
Registry last updated
Nov 3, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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