[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)
Alzheimer's Disease, Amnestic Mild Cognitive Impairment
About this trial
This is an interventional diagnostic trial for Alzheimer's Disease
Eligibility Criteria
Inclusion Criteria:
Part 1 and Part 2:
Male, or non-pregnant and non-breast feeding female; 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
- Post-menopausal female participant has been without menses for at least 1 year and has a documented follicle stimulating hormone (FSH) level in the postmenopausal range at screening
- Surgically sterile female participant may enroll in study if procedure (hysterectomy, oophorectomy, or tubal ligation) is documented/confirmed by medical records or protocol-defined examination/tests
- Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 3 months
Part 1 only:
- 18 to 55 years of age
- Body Mass Index (BMI) between 18-32 kg/m^2
- In good health based on medical history, physical examination, vital sign measurements, electrocardiogram (ECG) and laboratory safety tests
Part 2 only:
- 56 to 85 years of age
- Body weight <136 kg
- In stable medical condition based on medical history, physical examination, vital sign measurements and ECG
- In good health based on laboratory safety tests
- For some participants, willing to allow placement of an arterial catheter in the radial artery
For AD participants:
- Mini-Mental State Examination (MMSE) score ≤28
- 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, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
- Modified Hachinski score ≤4
- Screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD
- Able to read at a 6th grade level or equivalent and has a history of academic achievement and/or employment sufficient to exclude mental retardation
- Has a reliable informant/caregiver who is able to accompany the participant to all clinic visits and provide information to study investigator/staff via telephone contact
- If taking symptomatic treatment for AD, be on a stable dose for at least 4 weeks prior to study
For amnestic MCI participants:
- MMSE score ≥26
- A history of subjective memory decline before screening
- Objective impairment in verbal memory based on investigator's clinical assessment
- General cognitive function and activities of daily living sufficiently intact, so as not to meet criteria for mild AD dementia
- Modified Hachinski score ≤4
- MRI scan obtained at the screening visit is either normal or consistent with a diagnosis of AD
- Able to read at a 6th grade level or equivalent and has a history of academic achievement and/or employment sufficient to exclude mental retardation
For non-AD/non-MCI healthy elderly participants:
- MMSE score ≥27
- No history of subjective memory or other cognitive complaints
- No objective evidence of memory or cognitive impairment
Exclusion Criteria:
Part 1 and Part 2:
- Subject has participated in another investigational trial within 4 weeks of screening
- Subject 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
- History within 2 years prior to screening, or current evidence of a psychotic disorder or a major depressive disorder
- History of alcoholism or drug dependency/abuse within the last 2 years before screening
- 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
- Has positive test result for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
- Participant has had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
- QTc interval ≥470 msec (for males) or ≥480 msec (for females)
- Participant consumes >3 servings of alcohol a day
- Participant consumes >6 caffeine servings a day
- Participant 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
- Suffers from claustrophobia or an inability to tolerate confinement in small places and would be unable to undergo PET or (for Part 2 only) MRI scanning
Part 1 Only:
- Evidence of a clinically relevant neurological disorder at screening
- History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormality or disease
- Participant 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
Part 2 Only:
- Evidence of a clinically relevant neurological disorder other than AD at screening
- History or current evidence of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormality or disease, which is not adequately controlled through a stable medication regimen
- Participant 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
For participants undergoing arterial catheter placement only:
- Allergy to lidocaine which may be locally injected as an anesthetic
- Currently uses aspirin or aspirin-containing medications at doses exceeding 100 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs), which cannot be discontinued 2 weeks prior to dosing and throughout the course of the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Part 1, Healthy Young Participants
Part 2, Healthy Elderly Participants
Part 2, AD and Amnestic MCI Elderly Participants
Healthy young participants received a single intravenous (IV) dose of ~185 megabecquerel (MBq) [18F]MK-6240 in Part 1 of the study
Healthy elderly participants received a single IV dose of ~160 MBq [18F]MK-6240, in Part 2 of the study
AD and amnestic MCI participants received up to two IV doses of ~160 MBq [18F]MK-6240 in Part 2 of the study