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| ID | Type | Description | Link |
|---|---|---|---|
| 2009_630 | Other Identifier | Merck Registration Number |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I, Healthy Participants | Experimental | Healthy 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 Participants | Experimental | HE 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 Participants | Experimental | HE and AD participants will receive two separate IV doses of ~150 megabecquerel (MBq) [18F]MK-3328 in Part III of the study |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F]MK-3328 | Drug | IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With an Adverse Event (AE) | 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 | 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 | 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 | 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. |
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Inclusion Criteria:
Part I:
Parts II and III:
Exclusion Criteria:
Part I:
Parts II and III:
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | 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) |
| FG002 | 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) |
| FG003 | 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) |
| FG004 | 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) |
| FG005 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part I |
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| Part II |
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| Part III |
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Participants (Part I) + HE Participants (Part II/III) | 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 |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With an Adverse Event (AE) | 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. | All participants who received [18F]MK-3328 | Posted | Number | participants | Up to 14 days after last dose |
|
|
Up to 14 days after last dose
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Study 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Up to approximately 6 hours post dose |
| Mean Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) in AD Participants and HE Participants | 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 | 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 |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| AD Participants (Part II/III) |
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 |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Participants |
|
|
| Primary | Number of Participants Who Discontinued Study Due to an AE | 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. | All participants who received [18F]MK-3328 | Posted | Number | participants | Up to 14 days after last dose |
|
|
|
| Primary | Effective Dose of [18F]MK-3328 | 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). | All participants who received [18F]MK-3328 in Part I of study | Posted | Mean | Standard Deviation | µSv/MBq | Up to approximately 6 hours post dose |
|
|
|
| Primary | Organ Effective Dose of [18F]MK-3328 | 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. | All participants who received [18F]MK-3328 in Part I of study | Posted | Mean | Standard Deviation | µSv/MBq | Up to approximately 6 hours post dose |
|
|
|
| Primary | Mean Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) in AD Participants and HE Participants | 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). | All participants who received [18F]MK-3328 in Part II of study | Posted | Mean | Standard Deviation | ratio | 60-90 minutes post dose |
|
|
|
|
| Primary | Least Squares (LS) Mean [18F]MK-3328 SUVR in Brain Posterior Cingulate Gyrus in AD Participants and HE Participants | 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. | All participants who received a second dose of [18F]MK-3328 in Part III of study | Posted | Least Squares Mean | 95% Confidence Interval | ratio | 60-90 minutes after second dose |
|
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|
| 0 |
| 19 |
| 8 |
| 19 |
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Sensory loss | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 15.1 | Systematic Assessment |
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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.
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| Title | Measurements |
|---|---|
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| Gallbladder Wall |
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| Lower Large Intestine Wall |
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| Small Intestine |
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| Stomach Wall |
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| Upper Large Intestine Wall |
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| Heart Wall |
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| Kidneys |
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| Liver |
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| Lungs |
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| Muscle |
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| Ovaries |
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| Pancreas |
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| Red Marrow |
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| Osteogenic Cells |
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| Skin |
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| Spleen |
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| Testes |
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| Thymus |
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| Thyroid |
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| Urinary Bladder Wall |
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| Uterus |
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| Rest of Body |
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