Study to Assess the Safety, Tolerability, Pharmacokinetics of E2027 in Healthy Adult and Elderly Subjects, and the Pharmacodynamics in Healthy Adult Subjects

The study will consist of 4 parts, Parts A, B, C, and D. Part A is a single ascending dose
(SAD) clinical pharmacology for evaluation of safety, tolerability, and PK characteristics
up to the MTD in healthy adult (greater than or equal to 18 years and less than or equal to
50 years old). In Part B, the PK and PD effects of E2027 on CSF cGMP are evaluated in
healthy adult (greater than or equal to 18 years and less than or equal to 50 years old).
Participants in 2nd cohort of Part B will participate in the evaluation of food effect in
Treatment Period 2. In Part C, the design is similar to Part A. This healthy elderly cohort
(greater than or equal to 65 years and less than or equal to 85 years old) will provide
bridging PK, safety, and tolerability data on E2027 compared to younger healthy participants
in Part A and Part B. Part D will be conducted in healthy Japanese adult participants
(greater than or equal to 20 years and less than or equal to 50 years old) and is designed
to bridge the PK, safety, and tolerability data of E2027 between Japanese and non-Japanese
participants. All parts of the study will have 2 phases: the Prerandomization Phase and the
Randomization Phase. The Prerandomization Phase will consist of a Screening Period and a
Baseline Period during which each participant's study eligibility will be determined and
baseline assessments will be conducted. The Randomization Phase will consist of the
Treatment Period and a Follow-Up Period. During the Treatment Period, participants will be
randomized to receive a single oral dose of either E2027 or placebo matching E2027.

Inclusion Criteria:

Part A and B only:

1. Nonsmoking, male or female, age greater than or equal to 18 years and less than or
equal to 50 years old at the time of informed consent

Part C only:

2. Nonsmoking, male or female, age greater than or equal to 65 years and less than or
equal to 85 years old at the time of informed consent

Part D only:

3. Nonsmoking, male or female, age greater than or equal to 20 years and less than or
equal to 50 years old at the time of informed consent

4. Born in Japan to Japanese parents and grandparents of Japanese descent

5. Been living outside Japan for less than 5 years

6. Lifestyle, including diet, has not changed significantly since leaving Japan

All parts:

7. Body mass index (BMI) greater than or equal to 18 and less than or equal to 30 kg/m2
at Screening

Exclusion Criteria:

1. Clinically significant illness that requires medical treatment within 8 weeks or a
clinically significant infection that requires medical treatment within 4 weeks of
dosing

2. Females who are breastfeeding or pregnant at Screening or Baseline

3. If females of childbearing potential who:

1. Had unprotected sexual intercourse within 30 days before study entry and do not
agree to use a highly effective method of contraception

2. Are currently abstinent, and do not agree to use a double barrier method or
refrain from sexual activity

4. Males who have not had a successful vasectomy (confirmed azoospermia) or they and
their female partners do not meet the criteria above. No sperm donation is allowed
during the study period or for 28 days after study drug discontinuation.

5. Evidence of disease that may influence the outcome of the study within 4 weeks before
dosing

6. Any history of abdominal surgery that may affect PK profiles of E2027

7. Any clinically abnormal symptom or organ impairment found by medical history,
physical examinations, vital signs, ECG finding, or laboratory test results that
requires medical treatment at Screening or Baseline

8. A prolonged QT/QTc interval (QTc greater than 450 ms) demonstrated on ECG at
Screening or Baseline

9. Persistent systolic blood pressure greater than 130 mmHg or diastolic blood pressure
greater than 85 mm Hg at Screening or Baseline (Parts A, B, and D)

10. Persistent systolic blood pressure greater than 140 mmHg or diastolic blood pressure
greater than 90 mm Hg at Screening or Baseline (Part C)

11. Heart rate less than 50 or more than 100 beats/min at Screening or Baseline

12. History of prolonged QT/QTc interval

13. Left bundle branch block

14. History of myocardial infarction or active ischemic heart disease

15. History of clinically significant arrhythmia or uncontrolled arrhythmia

16. Known history of clinically significant drug allergy at Screening or Baseline

17. Known history of food allergies or presently experiencing significant seasonal or
perennial allergy at Screening or Baseline

18. Known to be human immunodeficiency virus (HIV) positive at Screening

19. Active viral hepatitis (A, B or C) as demonstrated by positive serology at Screening

20. History of drug or alcohol dependency or abuse within the 2 years before Screening,
or those who have a positive urine drug or alcohol test at Screening or Baseline

21. Intake of caffeinated beverages or food within 72 hours before dosing

22. Intake of nutritional supplements, juice, and herbal preparations or other foods or
beverages that may affect the various drug metabolizing enzymes and transporters
within 1 week before dosing

23. Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing

24. Use of prescription drugs within 4 weeks before dosing

25. Intake of over-the-counter (OTC) medications within 2 weeks before dosing

26. Currently enrolled in another clinical trial or used any investigational drug or
device within 30 days (or 5 half-lives, whichever is longer) preceding informed
consent

27. Engagement in strenuous exercise within 2 weeks before check-in (eg, marathon
runners, weight lifters, etc.)

28. Any contraindication to continuous CSF sampling via indwelling lumbar catheter (Part
B only)