Trial Outcomes & Findings for Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001) (NCT NCT00954538)
NCT ID: NCT00954538
Last Updated: 2015-11-03
Results Overview
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.
COMPLETED
PHASE1
19 participants
Up to 14 days after last dose
2015-11-03
Participant Flow
Participant milestones
| Measure |
Healthy Participants (Part I Only)
Healthy participants received a single intravenous (IV) dose of \~150 megabecquerel (MBq) \[18F\]MK-3328, followed by Positron Emission Tomography (PET) imaging of the whole body (Part I)
|
Healthy Elderly (HE) Participants (Part II Only)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
Alzheimer's Disease (AD) Participants (Part II Only)
AD participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
HE Participants (Part III Only)
HE participants received up to two separate IV doses of \~150 MBq \[18F\]MK-3328; each dose was followed by PET imaging of the brain (Part III)
|
AD Participants (Part III Only)
AD participants received up to two separate IV doses of \~150 MBq \[18F\]MK-3328; each dose was followed by PET imaging of the brain (Part III)
|
HE Participants (Part II + III)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II) / HE Participants who completed Part II could receive a second IV dose of \~150 MBq \[18F\]MK-3328 in Part III; this dose was followed by PET imaging of the brain
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|---|---|---|---|---|---|---|
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Part I
STARTED
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3
|
0
|
0
|
0
|
0
|
0
|
|
Part I
COMPLETED
|
3
|
0
|
0
|
0
|
0
|
0
|
|
Part I
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II
STARTED
|
0
|
1
|
3
|
0
|
0
|
2
|
|
Part II
COMPLETED
|
0
|
1
|
3
|
0
|
0
|
2
|
|
Part II
NOT COMPLETED
|
0
|
0
|
0
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0
|
0
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0
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|
Part III
STARTED
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0
|
0
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0
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4
|
6
|
2
|
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Part III
COMPLETED
|
0
|
0
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0
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4
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5
|
2
|
|
Part III
NOT COMPLETED
|
0
|
0
|
0
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0
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1
|
0
|
Reasons for withdrawal
| Measure |
Healthy Participants (Part I Only)
Healthy participants received a single intravenous (IV) dose of \~150 megabecquerel (MBq) \[18F\]MK-3328, followed by Positron Emission Tomography (PET) imaging of the whole body (Part I)
|
Healthy Elderly (HE) Participants (Part II Only)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
Alzheimer's Disease (AD) Participants (Part II Only)
AD participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
HE Participants (Part III Only)
HE participants received up to two separate IV doses of \~150 MBq \[18F\]MK-3328; each dose was followed by PET imaging of the brain (Part III)
|
AD Participants (Part III Only)
AD participants received up to two separate IV doses of \~150 MBq \[18F\]MK-3328; each dose was followed by PET imaging of the brain (Part III)
|
HE Participants (Part II + III)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II) / HE Participants who completed Part II could receive a second IV dose of \~150 MBq \[18F\]MK-3328 in Part III; this dose was followed by PET imaging of the brain
|
|---|---|---|---|---|---|---|
|
Part III
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001)
Baseline characteristics by cohort
| Measure |
Healthy Participants (Part I) + HE Participants (Part II/III)
n=10 Participants
This group includes Healthy participants (Part I) and HE participants (Part II/III). Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
AD Participants (Part II/III)
n=9 Participants
This group includes AD participants (Part II/III). Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of brain
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.5 Years
STANDARD_DEVIATION 6.3 • n=5 Participants
|
70.7 Years
STANDARD_DEVIATION 5.5 • n=7 Participants
|
65.8 Years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 14 days after last dosePopulation: All participants who received \[18F\]MK-3328
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.
Outcome measures
| Measure |
All Study Participants
n=19 Participants
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
HE Participants (Part II)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
|---|---|---|
|
Number of Participants With an Adverse Event (AE)
|
8 participants
|
—
|
PRIMARY outcome
Timeframe: Up to 14 days after last dosePopulation: All participants who received \[18F\]MK-3328
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.
Outcome measures
| Measure |
All Study Participants
n=19 Participants
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
HE Participants (Part II)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
|---|---|---|
|
Number of Participants Who Discontinued Study Due to an AE
|
0 participants
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 6 hours post dosePopulation: All participants who received \[18F\]MK-3328 in Part I of study
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).
Outcome measures
| Measure |
All Study Participants
n=3 Participants
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
HE Participants (Part II)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
|---|---|---|
|
Effective Dose of [18F]MK-3328
|
18.2 µSv/MBq
Standard Deviation 2.0
|
—
|
PRIMARY outcome
Timeframe: Up to approximately 6 hours post dosePopulation: All participants who received \[18F\]MK-3328 in Part I of study
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.
Outcome measures
| Measure |
All Study Participants
n=3 Participants
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
HE Participants (Part II)
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
|---|---|---|
|
Organ Effective Dose of [18F]MK-3328
Adrenals
|
0.0404 µSv/MBq
Standard Deviation 0.0147
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Brain
|
0.0635 µSv/MBq
Standard Deviation 0.0192
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Breasts
|
0.307 µSv/MBq
Standard Deviation 0.0468
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Gallbladder Wall
|
0 µSv/MBq
Standard Deviation 0
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Lower Large Intestine Wall
|
2.57 µSv/MBq
Standard Deviation 0.101
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Small Intestine
|
0.149 µSv/MBq
Standard Deviation 0.0716
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Stomach Wall
|
1.25 µSv/MBq
Standard Deviation 0.195
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Upper Large Intestine Wall
|
0.519 µSv/MBq
Standard Deviation 0.577
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Heart Wall
|
0 µSv/MBq
Standard Deviation 0
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Kidneys
|
0.963 µSv/MBq
Standard Deviation 1.38
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Liver
|
1.35 µSv/MBq
Standard Deviation 0.302
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Lungs
|
1.71 µSv/MBq
Standard Deviation 0.204
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Muscle
|
0.0268 µSv/MBq
Standard Deviation 0.0103
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Ovaries
|
3.06 µSv/MBq
Standard Deviation 0.226
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Pancreas
|
0.0399 µSv/MBq
Standard Deviation 0.0152
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Red Marrow
|
2.36 µSv/MBq
Standard Deviation 0.265
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Osteogenic Cells
|
0.181 µSv/MBq
Standard Deviation 0.0200
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Skin
|
0.0575 µSv/MBq
Standard Deviation 0.00864
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Spleen
|
0.0445 µSv/MBq
Standard Deviation 0.0133
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Testes
|
0 µSv/MBq
Standard Deviation 0
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Thymus
|
0.0247 µSv/MBq
Standard Deviation 0.00904
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Thyroid
|
0.675 µSv/MBq
Standard Deviation 0.0864
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Urinary Bladder Wall
|
2.75 µSv/MBq
Standard Deviation 0.598
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Uterus
|
0.0502 µSv/MBq
Standard Deviation 0.0229
|
—
|
|
Organ Effective Dose of [18F]MK-3328
Rest of Body
|
0 µSv/MBq
Standard Deviation 0
|
—
|
PRIMARY outcome
Timeframe: 60-90 minutes post dosePopulation: All participants who received \[18F\]MK-3328 in Part II of study
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).
Outcome measures
| Measure |
All Study Participants
n=3 Participants
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
HE Participants (Part II)
n=3 Participants
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
|---|---|---|
|
Mean Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) in AD Participants and HE Participants
|
1.75 ratio
Standard Deviation 0.14 • Interval 1.33 to 1.61
|
1.34 ratio
Standard Deviation 0.07 • Interval 1.23 to 1.48
|
PRIMARY outcome
Timeframe: 60-90 minutes after second dosePopulation: All participants who received a second dose of \[18F\]MK-3328 in Part III of study
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.
Outcome measures
| Measure |
All Study Participants
n=5 Participants
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
HE Participants (Part II)
n=6 Participants
HE participants received a single IV dose of \~150 MBq \[18F\]MK-3328, followed by PET imaging of the brain (Part II)
|
|---|---|---|
|
Least Squares (LS) Mean [18F]MK-3328 SUVR in Brain Posterior Cingulate Gyrus in AD Participants and HE Participants
|
1.47 ratio
Interval 1.33 to 1.61
|
1.35 ratio
Interval 1.23 to 1.48
|
Adverse Events
All Study Participants
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
All Study Participants
n=19 participants at risk
Participants were administered one or two IV doses of \~150 MBq \[18F\]MK-3328; all doses were followed by PET imaging of whole body or brain
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
1/19 • Up to 14 days after last dose
|
|
Gastrointestinal disorders
Nausea
|
5.3%
1/19 • Up to 14 days after last dose
|
|
General disorders
Feeling hot
|
5.3%
1/19 • Up to 14 days after last dose
|
|
Infections and infestations
Urinary tract infection
|
15.8%
3/19 • Up to 14 days after last dose
|
|
Nervous system disorders
Dysgeusia
|
5.3%
1/19 • Up to 14 days after last dose
|
|
Nervous system disorders
Headache
|
15.8%
3/19 • Up to 14 days after last dose
|
|
Nervous system disorders
Sensory loss
|
5.3%
1/19 • Up to 14 days after last dose
|
|
General disorders
Injection site pain
|
5.3%
1/19 • Up to 14 days after last dose
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
- Publication restrictions are in place
Restriction type: OTHER