[18F]MK-6240 Positron Emission Tomography (PET) Tracer First-in-Human Validation Study (MK-6240-001)

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