Alzheimer's Disease
Conditions
Brief summary
The purpose of this open-label, 3-part study is to investigate the safety and efficacy of \[11C\]MK-6884 as a positron emission tomography (PET) imaging agent for quantifying muscarinic 4 (M4) positive allosteric modulator (PAM) receptor density in brain regions of interest. The study will enroll healthy participants (Parts 1 and 2) and participants with Alzheimer's Disease (AD) (Part 3). The primary efficacy hypothesis is that the average intra-subject test-retest (T-RT) variability of tracer uptake in brain regions of interest is ≤20%.
Interventions
DRUG[11C]MK-6884
IV bolus dose of \ 370 MBq \[11C\]MK-6884
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1, 2 and 3: * Male, or non-pregnant and non-breast feeding female of 18 to 55 years of age (Part 1) or 55 to 85 years of age (Parts 2 and 3); in addition: * Male participant who is sexually active with females of childbearing potential must be willing to use a condom from the first dose of study drug until 3 months post the last dose of study drug * Female participant with reproductive potential must have serum β-human chorionic gonadotropin (β-hCG) test result consistent with non-pregnant state at screening and agree to use two acceptable methods of birth control beginning at screening visit, during study and until 2 weeks after the last dose of study drug * Female participant of non-childbearing potential must be post-menopausal female (participant has been without menses for at least 1 year and has a follicle stimulating hormone \[FSH\] level in the postmenopausal range at screening), or surgically sterile female (status post hysterectomy, oophorectomy, or tubal ligation) * Body Mass Index (BMI) ≤35 kg/m\^2, with height ≤195 cm and weight ≤136 kg * In good health (Part 1) or generally healthy (Parts 2 and 3) based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG) * Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 3 months Part 2 Only: * Willing to allow placement of an arterial catheter in the radial artery * Mini Mental Status Examination (MMSE) score ≥27 * No history of subjective memory or other cognitive complaints * No objective evidence of memory or cognitive impairment Part 3 Only: * Moderate to severe AD as defined by: * MMSE score ≤20 * Meets National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD * Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria for AD * Rosen-Modified Hachinski score ≤4 * Screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD * Clear history of cognitive and functional decline over ≥1 year * On a stable dose of one of protocol-defined acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil and rivastigmine) for symptomatic treatment of AD. Dose must be stable for at least the last 4 weeks before screening * Has a reliable trial partner/caregiver who is able to accompany the participant to all clinic visits, if needed, and able to provide information to study investigator/staff via telephone contact
Exclusion criteria
Part 1, 2, and 3: * Mentally or legally incapacitated, has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years, except (for Part 3 only) for psychiatric disorders associated with AD * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases, unless (for Part 2 and 3 only) adequately controlled through a stable medication regimen * History of cancer * History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. For Part 2, this includes any known allergy to lidocaine which may be used as an anesthetic for the placement of the arterial catheter * Has positive test result for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV) * Has had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening * Has participated in another investigational trial within 4 weeks of screening * Corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females) * Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies, beginning approximately 2 weeks prior to administration of the initial dose of study drug and throughout the study. * Consumes \>3 servings of alcohol a day * Consumes \>6 caffeine servings a day * Is currently a regular or recreational user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months * Has participated in a PET research study or other study involving administration of a radioactive substance or ionizing radiation within 12 months prior to screening or has undergone an extensive radiological examination within this period * Suffers from claustrophobia or an inability to tolerate confinement in small places and would be unable to undergo MRI or PET scanning Part 2 Only: \- Has been administered an AChEI within the prior 3 months or will require administration of an AChEI during study Part 3 Only: * Has been administered galantamine within the prior 7 days or will require administration of galantamine during study * History within 2 years prior to screening, or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition * History within 2 years prior to screening, or current evidence of a psychotic disorder or a major depressive disorder Part 2 and 3 Only: \- Has or is suspected to have implanted or embedded metal objects, or fragments in the head or body that would present a risk during the MRI scanning procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing an Adverse Event (AE) | Up to 15 days | The number of participants experiencing an adverse event (AE) was assessed. An AE is defined as any unfavorable and unintended medical occurrence, sign, symptom, or disease temporally associated with the use of a pharmaceutical product or protocol-specified procedure, whether or not considered related to the pharmaceutical product or protocol-specified procedure. Any worsening of a preexisting condition, temporally associated with the use of the Sponsor's product, is also an AE. |
| Number of Participants Discontinuing the Study Due to an Adverse Event (AE) | Up to 15 days | The number of participants discontinuing the study due to an AE was assessed. An AE is defined as any unfavorable and unintended medical occurrence, sign, symptom, or disease temporally associated with the use of a pharmaceutical product or protocol-specified procedure, whether or not considered related to the pharmaceutical product or protocol-specified procedure. Any worsening of a preexisting condition, temporally associated with the use of the Sponsor's product, is also an AE. |
| [Part 1] Mean Effective Dose of [11C]MK-6884 | Up to 2 hours post-dose | Mean effective dose (ED) of \[11C\]MK-6884 was calculated as a measure of risk associated with exposure of the whole body (WB) to low levels of ionizing radiation. Following \[11C\]MK-6884 injection, WB positron emission tomography (PET) scans were collected to visually identify organs absorbing \[11C\]MK-6884 in significant amounts. Around identified organs, three-dimensional (3D) volumes were drawn to estimate the percentage of injected activity absorbed. These data were converted into time-activity curves (TACs) and retention of radioactivity in these regions was entered into a human biodistribution model to determine ED of \[11C\]MK-6884. ED is expressed in units millisieverts (mSv) / MBq. |
| [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Up to 2 hours post dose | Mean organ ED of \[11C\]MK-6884 was calculated as a measure of risk associated with exposure of individual organs to low levels of ionizing radiation. Following \[11C\]MK-6884 injection, WB PET scans were collected to visually identify organs absorbing \[11C\]MK-6884 in significant amounts. Around identified organs, 3D volumes were drawn to estimate the percentage of injected activity absorbed. These data were converted into TACs and retention of radioactivity in these regions was used to calculate organ-specific ED of \[11C\]MK-6884. For sex organs (testes/ovaries), organ EDs were derived for participants of the respective sex. However, organ ED for the uterus was estimable in all participants as the male radiologic phantom was sufficiently hermaphroditic. |
| [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Up to 90 minutes post dose | Mean BPND of \[11C\]MK-6884 in each brain ROI was assessed. BPND is the ratio at equilibrium of specifically bound \[11C\]MK-6884 to that of non-displaceable \[11C\]MK-6884 in tissue. At time 0, a single IV bolus of \[11\]MK-6884 is administered and PET scanning initiated, yielding brain regional TACs. These TACs are then used to determine peak standard uptake value (SUV) and area under the curve (AUC) in order to quantify brain regional \[11C\]MK-6884 uptake. The target region BPND is estimated using the cerebellum as the reference region with the transient equilibrium tissue ratio (TE-TR) method. Higher values indicate increased specific \[11C\]MK-6884 binding in the brain ROI. |
| [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Up to 24 hours post dose | Intra-subject T-RT variability in BPND of \[11C\]MK-6884 in each brain ROI was assessed. For each healthy elderly participant receiving 2 doses of \[11C\]MK-6884 in study Part 2, the BPND calculated during the first dose (BPND-1) was compared to the BPND calculated during the second dose (BPND-2) to determine the percent T-RT variability of the BPND of \[11C\]MK-6884 for each brain ROI. Percent T-RT variability = \[absolute value (BPND-1 - BPND-2) / (average BPND)\] \* 100. A percent T-RT variability = 0, indicates no variability between BPND-1 and BPND-2. |
| [Part 3] Mean Regional Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest | Up to 90 minutes post dose | Mean BPND of \[11C\]MK-6884 in each brain ROI was assessed. BPND is the ratio at equilibrium of specifically bound \[11C\]MK-6884 to that of non-displaceable \[11C\]MK-6884 in tissue. At time 0, a single IV bolus of \[11\]MK-6884 is administered and PET scanning initiated, yielding brain regional TACs. These TACs are then used to determine SUV and AUC in order to quantify brain regional \[11C\]MK-6884 uptake. The target region BPND is estimated using the cerebellum as the reference region with the TE-TR method. Higher values indicate increased specific \[11C\]MK-6884 binding in the brain ROI. |
Participant flow
Recruitment details
Healthy participants (Part 1), healthy elderly participants (Part 2), and participants with Alzheimer's Disease (AD; Part 3) were enrolled in this study.
Pre-assignment details
N=20 participants were enrolled, with N=20 receiving ≥1 dose of \[11C\]MK-6884. N=1 participant in Part 2 withdrew from study before receiving the second dose of \[11C\]MK-6884.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Healthy Participants Healthy participants receive a single IV dose of \
370 MBq \[11C\]MK-6884 in Part 1 of the study. | 3 |
| Part 2, Healthy Elderly Participants Healthy elderly participants receive two separate IV doses of \
370 MBq \[11C\]MK-6884 in Part 2 of the study. Administration of the two doses is separated by at least 3 hours. | 7 |
| Part 3, Participants With AD Participants with AD receive a single IV dose of \
370 MBq \[11C\]MK-6884 in Part 3 of the study. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1, Healthy Participants | Part 2, Healthy Elderly Participants | Part 3, Participants With AD | Total |
|---|---|---|---|---|
| Age, Continuous | 25.3 Years STANDARD_DEVIATION 2.1 | 62.6 Years STANDARD_DEVIATION 5.4 | 67.6 Years STANDARD_DEVIATION 5.2 | 59.5 Years STANDARD_DEVIATION 15.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 7 | 0 / 10 |
| other Total, other adverse events | 1 / 3 | 4 / 7 | 1 / 10 |
| serious Total, serious adverse events | 0 / 3 | 1 / 7 | 0 / 10 |
Outcome results
Primary
Number of Participants Discontinuing the Study Due to an Adverse Event (AE)
The number of participants discontinuing the study due to an AE was assessed. An AE is defined as any unfavorable and unintended medical occurrence, sign, symptom, or disease temporally associated with the use of a pharmaceutical product or protocol-specified procedure, whether or not considered related to the pharmaceutical product or protocol-specified procedure. Any worsening of a preexisting condition, temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to 15 days
Population: Includes all participants receiving ≥1 dose of \[11C\]MK-6884 in Parts 1, 2, or 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Healthy Participants | Number of Participants Discontinuing the Study Due to an Adverse Event (AE) | 0 Participants |
| Part 2, Healthy Elderly Participants | Number of Participants Discontinuing the Study Due to an Adverse Event (AE) | 0 Participants |
| Part 3, Participants With AD | Number of Participants Discontinuing the Study Due to an Adverse Event (AE) | 0 Participants |
Primary
Number of Participants Experiencing an Adverse Event (AE)
The number of participants experiencing an adverse event (AE) was assessed. An AE is defined as any unfavorable and unintended medical occurrence, sign, symptom, or disease temporally associated with the use of a pharmaceutical product or protocol-specified procedure, whether or not considered related to the pharmaceutical product or protocol-specified procedure. Any worsening of a preexisting condition, temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Up to 15 days
Population: Includes all participants receiving ≥1 dose of \[11C\]MK-6884 in Parts 1, 2, or 3.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Healthy Participants | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
| Part 2, Healthy Elderly Participants | Number of Participants Experiencing an Adverse Event (AE) | 5 Participants |
| Part 3, Participants With AD | Number of Participants Experiencing an Adverse Event (AE) | 1 Participants |
Primary
[Part 1] Mean Effective Dose of [11C]MK-6884
Mean effective dose (ED) of \[11C\]MK-6884 was calculated as a measure of risk associated with exposure of the whole body (WB) to low levels of ionizing radiation. Following \[11C\]MK-6884 injection, WB positron emission tomography (PET) scans were collected to visually identify organs absorbing \[11C\]MK-6884 in significant amounts. Around identified organs, three-dimensional (3D) volumes were drawn to estimate the percentage of injected activity absorbed. These data were converted into time-activity curves (TACs) and retention of radioactivity in these regions was entered into a human biodistribution model to determine ED of \[11C\]MK-6884. ED is expressed in units millisieverts (mSv) / MBq.
Time frame: Up to 2 hours post-dose
Population: Includes only healthy participants in Part 1 (N=3). Per protocol, participants in Parts 2 and 3 were not tested for ED of \[11C\]MK-6884 and are excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Healthy Participants | [Part 1] Mean Effective Dose of [11C]MK-6884 | 0.0072 mSv / MBq | Standard Deviation 0.00127 |
Primary
[Part 1] Mean Organ Effective Dose of [11C]MK-6884
Mean organ ED of \[11C\]MK-6884 was calculated as a measure of risk associated with exposure of individual organs to low levels of ionizing radiation. Following \[11C\]MK-6884 injection, WB PET scans were collected to visually identify organs absorbing \[11C\]MK-6884 in significant amounts. Around identified organs, 3D volumes were drawn to estimate the percentage of injected activity absorbed. These data were converted into TACs and retention of radioactivity in these regions was used to calculate organ-specific ED of \[11C\]MK-6884. For sex organs (testes/ovaries), organ EDs were derived for participants of the respective sex. However, organ ED for the uterus was estimable in all participants as the male radiologic phantom was sufficiently hermaphroditic.
Time frame: Up to 2 hours post dose
Population: Includes only healthy participants in Part 1 (N=3), having estimable data for the individual organ. Per protocol, participants in Parts 2 and 3 were not tested for organ ED of \[11C\]MK-6884 and are excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Heart Wall | 0 mSv / MBq | Standard Deviation 0 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Skin | 0.0000145 mSv / MBq | Standard Deviation 0.00000409 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Adrenals | 0.00000924 mSv / MBq | Standard Deviation 0.0000019 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Brain | 0.00000666 mSv / MBq | Standard Deviation 0.00000135 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Breasts | 0.0000804 mSv / MBq | Standard Deviation 0.0000212 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Gallbladder Wall | 0 mSv / MBq | Standard Deviation 0 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Lower Large Intestine Wall | 0.000499 mSv / MBq | Standard Deviation 0.000146 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Small Intestine | 0.000802 mSv / MBq | Standard Deviation 0.000217 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Stomach Wall | 0.000357 mSv / MBq | Standard Deviation 0.0000962 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Upper Large Intestine Wall | 0.0000312 mSv / MBq | Standard Deviation 0.00000782 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Kidneys | 0.0000476 mSv / MBq | Standard Deviation 0.00000571 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Liver | 0.00104 mSv / MBq | Standard Deviation 0.000236 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Lungs | 0.000709 mSv / MBq | Standard Deviation 0.000228 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Muscle | 0.00000541 mSv / MBq | Standard Deviation 0.00000144 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Ovaries (Female Participants Only) | 0.00126 mSv / MBq | Standard Deviation 0 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Pancreas | 0.00000938 mSv / MBq | Standard Deviation 0.00000215 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Red Marrow | 0.000541 mSv / MBq | Standard Deviation 0.0000553 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Osteogenic Cells | 0.000041 mSv / MBq | Standard Deviation 0.0000106 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Spleen | 0.0000256 mSv / MBq | Standard Deviation 0.0000202 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Testes (Male Participants Only) | 0.0017 mSv / MBq | Standard Deviation 0.000573 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Thymus | 0.00000463 mSv / MBq | Standard Deviation 0.00000118 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Thyroid | 0.0000732 mSv / MBq | Standard Deviation 0.0000218 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Urinary Bladder Wall | 0.00135 mSv / MBq | Standard Deviation 0.00045 |
| Part 1, Healthy Participants | [Part 1] Mean Organ Effective Dose of [11C]MK-6884 | Uterus | 0.0000124 mSv / MBq | Standard Deviation 0.00000334 |
Primary
[Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI)
Intra-subject T-RT variability in BPND of \[11C\]MK-6884 in each brain ROI was assessed. For each healthy elderly participant receiving 2 doses of \[11C\]MK-6884 in study Part 2, the BPND calculated during the first dose (BPND-1) was compared to the BPND calculated during the second dose (BPND-2) to determine the percent T-RT variability of the BPND of \[11C\]MK-6884 for each brain ROI. Percent T-RT variability = \[absolute value (BPND-1 - BPND-2) / (average BPND)\] \* 100. A percent T-RT variability = 0, indicates no variability between BPND-1 and BPND-2.
Time frame: Up to 24 hours post dose
Population: Includes only healthy elderly participants in Part 2 receiving 2 doses of \[11C\]MK-6884 who sufficiently comply with study protocol (N=6). Per protocol, participants in Parts 1 and 3 were not tested for intra-subject T-RT variability of BPND of \[11C\]MK-6884 and are excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2, Healthy Elderly Participants | [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Putamen | 14.1 Percent variability | Standard Deviation 9 |
| Part 2, Healthy Elderly Participants | [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Striatum | 11.1 Percent variability | Standard Deviation 9.2 |
| Part 2, Healthy Elderly Participants | [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Frontal Cortex | 16.0 Percent variability | Standard Deviation 7.8 |
| Part 2, Healthy Elderly Participants | [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Temporal Cortex | 10.9 Percent variability | Standard Deviation 13.7 |
| Part 2, Healthy Elderly Participants | [Part 2] Intra-subject Test-Retest (T-RT) Variability of Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Hippocampus | 24.9 Percent variability | Standard Deviation 15.3 |
Primary
[Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI)
Mean BPND of \[11C\]MK-6884 in each brain ROI was assessed. BPND is the ratio at equilibrium of specifically bound \[11C\]MK-6884 to that of non-displaceable \[11C\]MK-6884 in tissue. At time 0, a single IV bolus of \[11\]MK-6884 is administered and PET scanning initiated, yielding brain regional TACs. These TACs are then used to determine peak standard uptake value (SUV) and area under the curve (AUC) in order to quantify brain regional \[11C\]MK-6884 uptake. The target region BPND is estimated using the cerebellum as the reference region with the transient equilibrium tissue ratio (TE-TR) method. Higher values indicate increased specific \[11C\]MK-6884 binding in the brain ROI.
Time frame: Up to 90 minutes post dose
Population: Includes only healthy elderly participants in Part 2 receiving 2 doses of \[11C\]MK-6884 who sufficiently comply with study protocol (N=6). Per protocol, participants in Part 1 were not tested for mean BPND of \[11C\]MK-6884 and are excluded. Mean BPND data for Part 3 participants are presented in a separate table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2, Healthy Elderly Participants | [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Putamen | 1.15 Ratio | Standard Deviation 0.14 |
| Part 2, Healthy Elderly Participants | [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Striatum | 0.96 Ratio | Standard Deviation 0.13 |
| Part 2, Healthy Elderly Participants | [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Frontal Cortex | 0.92 Ratio | Standard Deviation 0.15 |
| Part 2, Healthy Elderly Participants | [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Temporal Cortex | 0.92 Ratio | Standard Deviation 0.12 |
| Part 2, Healthy Elderly Participants | [Part 2] Mean Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest (ROI) | Hippocampus | 0.45 Ratio | Standard Deviation 0.11 |
Primary
[Part 3] Mean Regional Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest
Mean BPND of \[11C\]MK-6884 in each brain ROI was assessed. BPND is the ratio at equilibrium of specifically bound \[11C\]MK-6884 to that of non-displaceable \[11C\]MK-6884 in tissue. At time 0, a single IV bolus of \[11\]MK-6884 is administered and PET scanning initiated, yielding brain regional TACs. These TACs are then used to determine SUV and AUC in order to quantify brain regional \[11C\]MK-6884 uptake. The target region BPND is estimated using the cerebellum as the reference region with the TE-TR method. Higher values indicate increased specific \[11C\]MK-6884 binding in the brain ROI.
Time frame: Up to 90 minutes post dose
Population: Includes only participants with AD in Part 3 receiving \[11C\]MK-6884 who sufficiently comply with study protocol (N=10). Per protocol, participants in Part 1 were not tested for mean BPND of \[11C\]MK-6884 and are excluded. Mean BPND data for Part 2 participants are presented in a separate table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 3, Participants With AD | [Part 3] Mean Regional Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest | Frontal Cortex | 0.74 Ratio | Standard Deviation 0.2 |
| Part 3, Participants With AD | [Part 3] Mean Regional Non-displaceable Binding Potential (BPND) of [11C]MK-6884 in Brain Regions of Interest | Striatum | 0.98 Ratio | Standard Deviation 0.2 |