Alzheimer's DiseasePhase 1NCT00954538
Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK3328 (MK-3328-001)
A Phase 1 study testing [18F]MK-3328 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- [18F]MK-3328
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- No sites listed yet
- Study dates
- Aug 2009to May 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
Show all 9Show fewer
- 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)
Who cannot join
- 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
About this study
Official 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
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.
- Conditions
- Alzheimer's Disease
- Being tested
- [18F]MK-3328
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]MK-3328Drug
IV dose of ~150 megabecquerel (MBq) [18F]MK-3328
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: [18F]MK-3328 |
| 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 Receives: Drug: [18F]MK-3328 |
| 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 Receives: Drug: [18F]MK-3328 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 60-90 minutes after second dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00954538
- Sponsor's protocol ID
- 3328-001
- Other IDs
- 2009_630
- Status last verified
- Nov 2015
- First submitted
- 6 Aug 2009
- Last updated
- 3 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00954538
- Acronym / sponsor ID
- 3328-001
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Aug 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 7 Aug 2009 (estimated)
- Results
- Posted 5 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part I, Healthy Participants | Experimental | Drug: [18F]MK-3328Healthy 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 | Drug: [18F]MK-3328HE 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 | Drug: [18F]MK-3328HE and AD participants will receive two separate IV doses of ~150 megabecquerel (MBq) [18F]MK-3328 in Part III of the study |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
- Male or female of non-reproductive potential at least 55 years of age
Key exclusion criteria (7 listed)
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]MK-3328IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 | Drug | Part I, Healthy Participants, Part II, HE and AD Participants, Part III, HE and AD Participants |
Primary outcome
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.
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.
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).
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.
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).
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [18F]MK-3328 in people with Alzheimer's Disease, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With an Adverse Event (AE) (time frame: Up to 14 days after last dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2015.