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