Study of TAK-071 in Healthy Participants and Participants With Mild Cognitive Impairment/Mild Alzheimer Disease and Relative Bioavailability (BA) and Food Effect of TAK-071 in Healthy Participants

TAK-071 is being tested to find a safe and well-tolerated dose in healthy participants
(non-Japanese and Japanese) and participants with MCI or mild AD (non-Japanese).

The study will enroll approximately 186 participants. The study consists of 4 parts:
Single-rising dose (SRD) part (Cohorts 1-6, and 18-22), multiple-rising dose (MRD) part
(Cohorts 7-15), Cohort 16 with 2-arm parallel design, and Cohort 17 relative bioavailability
and food effect 3 period crossover design. Cohorts 1-12 and 18-19, will have 8 randomized
participants, with 6 receiving TAK-071, and 2 receiving matching placebo. Cohorts 20-22 will
have 12 randomized participants with 3 receiving TAK-071 placebo+donepezil placebo, 3
receiving TAK-071 placebo+donepezil, and 6 receiving TAK-071+donepezil. Cohorts 13-15, will
have 6 randomized participants, with 5 receiving TAK-071, and 1 receiving matching placebo.
Selected cohorts (Cohorts 10 to 12) will be pretreated for 3 weeks with daily oral doses of
donepezil (5 mg QD), followed by continued daily oral donepezil dosing during the TAK-071
treatment period. The planned initial dose of TAK-071 for Cohort 1 is 1 mg and subsequent
dose levels to be determined by emerging safety, tolerability, and PK data in preceding
cohorts.

Participants in each cohort will be randomized to receive treatment with TAK-071 or matching
placebo using drug-in-capsule (DIC) in the morning following a minimum fast of 8 hours. In
Cohort 16, participants will be assigned to 1 of 2 possible treatments, TAK-071 or matching
placebo. In Cohort 17, 12 participants will be assigned to 1 of 3 treatment sequences (ABC,
BCA, or CAB) with treatment A being Fasted State and Capsule Formulation, Treatment B being
Fasted State and Tablet Formulation, and Treatment being C Fed State and Tablet Formulation
(10 mg tablet formulation). In Cohorts 20-22, participants will be administered as a single
dose of TAK-071 or placebo on Day 1, and a single dose of donepezil or placebo approximately
24 hours later on Day 2.

Inclusion Criteria:

1. Man or woman who weighs at least 50 kg and has a body mass index (BMI) from 18.0 to
30.0 kg/m^2, inclusive, at Screening. Participants should be aged 18 to 55 years,
inclusive (nonelderly at the time of informed consent and first study drug dose) for
Cohorts 1 to 12, and 17 to 22; 20 to 55 years, inclusive, for Cohorts 13 to 15; and 55
to 90 years, inclusive, for participants in Cohort 16.

2. For Cohorts 13 to 15 only: First-generation Japanese, defined as having been born in
Japan of Japanese parents and Japanese grandparents and living no more than 10 years
outside of Japan, with no significant change in lifestyle, including diet, while
living outside of Japan.

3. Cohort 16 only: Healthy elderly or participants with MCI or mild AD, who must have
Mini Mental State Examination (MMSE) score of 18 to 30, inclusive or 18 to 26
inclusive, respectively, and no biomarker data to contradict this diagnosis.
Participants with documented diagnosis of MCI or mild AD must be receiving ongoing
donepezil therapy (10 mg) in the evening for a minimum of 21 days prior to Check-in
(Day -1) or must consent to take donepezil dose titrated to at least 21 days of
treatment with 10 mg QD prior to Check-in.

Exclusion Criteria:

1. Has clinically significant (Cohorts 1 to 15 and 17 to 22) or uncontrolled (Cohort 16)
neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal
(GI), urologic, immunologic, endocrine, or psychiatric disease or other abnormality
(other than the disease being studied), which may impact the ability of the
participant to participate or potentially confound the study results.

2. Has a history of type 1 diabetes (Cohorts 1 to 22) or type 2 diabetes (Cohorts 1 to
15, 17 to 22) or hemoglobin A1c >6.5% at Screening. Note: participants with controlled
(hemoglobin A1c <7.0% at Screening) type 2 diabetes in Cohort 16 may participate in
the study.

3. Has a risk of suicide or suicidal ideation with intent and plan according to the
investigator's clinical judgment (affirmative answer to questions 4 and 5 of the
ideation section of the Columbia-Suicide Severity Rating Scale) or has made a suicide
attempt in the previous 6 months.

4. Cohort 16 only: Any significant neurologic disease (other than suspected incipient or
mild AD), such as Parkinson disease, stroke, transient ischemic attack, multi-infarct
dementia, Huntington disease, head trauma with clinically significant cognitive
sequelae, or chronic central nervous system infection, per investigator discretion.

5. Has current or recent (within 6 months) GI disease that would be expected to influence
the absorption of drugs (ie, a history of malabsorption, any surgical intervention
known to impact absorption [eg, bariatric surgery or bowel resection], esophageal
reflux, peptic ulcer disease, erosive esophagitis, or frequent [more than once per
week] occurrence of heartburn).