- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00954538
Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001)
November 2, 2015 updated by: Merck Sharp & Dohme LLC
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
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Part I, Healthy Participants
Healthy participants will receive a single intravenous (IV) dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part I of the study
|
IV dose of ~150 megabecquerel (MBq) [18F]MK-3328
|
EXPERIMENTAL: Part II, HE and AD Participants
HE and AD participants will receive a single IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part II of the study
|
IV dose of ~150 megabecquerel (MBq) [18F]MK-3328
|
EXPERIMENTAL: Part III, HE and AD Participants
HE and AD participants will receive two separate IV doses of ~150 megabecquerel (MBq) [18F]MK-3328 in Part III of the study
|
IV dose of ~150 megabecquerel (MBq) [18F]MK-3328
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 14 days after last dose
|
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.
|
Up to 14 days after last dose
|
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).
|
Up to approximately 6 hours post dose
|
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.
|
Up to approximately 6 hours post dose
|
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).
|
60-90 minutes post dose
|
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.
|
60-90 minutes after second dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2009
Primary Completion (ACTUAL)
May 1, 2011
Study Completion (ACTUAL)
May 1, 2011
Study Registration Dates
First Submitted
August 6, 2009
First Submitted That Met QC Criteria
August 6, 2009
First Posted (ESTIMATE)
August 7, 2009
Study Record Updates
Last Update Posted (ESTIMATE)
November 3, 2015
Last Update Submitted That Met QC Criteria
November 2, 2015
Last Verified
November 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3328-001
- 2009_630 (OTHER: Merck Registration Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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