A Study to Evaluate the Pharmacokinetics of E2609 and Its Metabolites in Subjects With Mild and Moderate Hepatic Impairment Compared With Healthy Subjects

Inclusion Criteria

1. Nonsmoking, male or female, ≥18 years and ≤70 years of age at the time of informed
consent, and with body mass index (BMI) of up to 40 kg/m2, inclusive.

2. For Cohorts 1 and 2: stable mild or moderate hepatic impairment conforming to
Child-Pugh class A or B, respectively, documented by medical history, physical
examination and 1 or more of the following diagnostic procedures documented in the
medical notes: liver biopsy, computed tomography (CT) scan, magnetic resonance
imaging (MRI), ultrasound, radionuclide liver/spleen scan, or abdominal laparoscopy.
Participants whose liver imaging was done more than 1 year ago or previous results
were not available, should have a liver ultrasound scan to ensure that the liver
structure is consistent with the diagnosis of hepatic impairment and that there are
no exclusionary features.

3. For Cohorts 1C and 2C: healthy participants matched to participants with mild or
moderate hepatic impairment with regard to age (±10 years), body weight (±20%), and
gender; and as determined by no clinically significant deviation from normal in
medical history, physical examination, electrocardiogram (ECG), and clinical
laboratory determinations.

Exclusion Criteria

For all Participants (Cohorts 1, 2, 1C, and 2C)

1. Females participants who are breastfeeding or pregnant at Screening or Baseline (as
documented by a positive beta-human chorionic gonadotropin [ß-hCG] test. A separate
baseline assessment is required if a negative screening pregnancy test was obtained
more than 72 hours before the dose of study drug.

2. Females of childbearing potential who:

- Had unprotected sexual intercourse within 30 days before study entry and who do
not agree to use a highly effective method of contraception (eg, total
abstinence, an intrauterine device, a double-barrier method [such as condom plus
diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or
have a vasectomized partner with confirmed azoospermia) throughout the entire
study period or for 28 days after study drug discontinuation.

- Are currently abstinent and do not agree to use a double-barrier method (as
previously described) or refrain from sexual activity during the study period or
for 28 days after study drug discontinuation .

- Are using hormonal contraceptives but are not on a stable dose of the same
hormonal contraceptive product except those containing estradiol for at least 4
weeks before dosing and who do not agree to use the same contraceptive during
the study or for 28 days after study drug discontinuation.

- Are using estradiol-containing hormonal contraceptives within 4 weeks before
dosing (NOTE: All females will be considered to be of childbearing potential
unless they are postmenopausal [amenorrheic for at least 12 consecutive months,
in the appropriate age group, and without other known or suspected cause] or
have been sterilized surgically [eg, bilateral tubal ligation, total
hysterectomy, or bilateral oophorectomy; all with surgery at least 1 month
before dosing]).

3. Males who have not had a successful vasectomy (unconfirmed azoospermia) or they and
their female partners do not meet the criteria specified in exclusion criterion 2
(eg, unwilling to refrain from sexual activity, not of childbearing potential or
practicing highly effective contraception throughout the study period or for 28 days
after study drug discontinuation).

4. Inability to tolerate oral medication.

5. Inability to be venipunctured and/or tolerate venous access. For Hepatically Impaired
Participants (Cohorts 1 and 2)

6. Any significant acute medical illness (such as new conditions or exacerbation or
pre-existing conditions) within 4 weeks before dosing.

7. Medical conditions which are not adequately and stably controlled on stable doses of
medications or which, in the clinical opinion of the investigator, may interfere with
study procedures or participant safety within 4 weeks before dosing; eg, psychiatric
disorders and disorders of the gastrointestinal tract, kidney, respiratory system,
endocrine system, hematological system, neurological system, or cardiovascular
system, or participants who have a congenital abnormality in metabolism. Participants
with history of seizures during adulthood are excluded. Participants with a history
of Gilbert's syndrome are excluded.

8. History of esophageal and gastric variceal bleeding within the past 3 months unless
the participant has completed a course of endoscopic therapy with the appropriate
documentation (eg, endoscopy report) of successful ablation of esophageal varices;
participants with esophageal varices may be included if not bleeding within the past
3 months or have been treated adequately by ablation therapy.

9. Spontaneous bacterial peritonitis within 3 months before dosing.

10. Treatment with plasmapheresis within 6 months before dosing.

11. Primarily cholestatic liver diseases (eg, primary biliary cirrhosis or primary
sclerosing cholangitis).

12. Current or recent (within 3 months before Screening) history of significant
gastrointestinal disease other than that secondary to hepatic impairment.

13. Autoimmune liver disease.

14. Active alcoholic hepatitis determined either clinically or by histology per the
discretion of the investigator.

15. History of hepatoma or metastatic disease of the liver.

16. Presence of severe ascites or edema.

17. Presence of hepatopulmonary syndrome or hydrothorax, or hepatorenal syndrome.

18. Known significant bleeding diathesis that could preclude multiple venipunctures
(International Normalized Ratio [INR] >2.5).

19. Any major surgery within 4 weeks before dosing.

20. Any history of abdominal surgery that may affect the pharmacokinetic (PK) of E2609
(eg, hepatectomy, nephrectomy, digestive organ resection, transjugular intrahepatic
portosystemic shunt [TIPS]) at Screening or Baseline (history of cholecystectomy need
not be exclusionary).

21. Donation of blood or plasma within 4 weeks before dosing.

22. Receipt of blood or blood products within 4 weeks before dosing.

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

24. Creatinine clearance <60 mL/min at Screening or Baseline, as calculated using
Cockroft and Gault equation.

25. Known history of clinically significant drug allergy at Screening.

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

27. History of drug or alcohol dependency or abuse within 4 weeks before Screening, or
those who have a positive urine drug test or breath (or urine) alcohol test at
Screening or Baseline unless a prescribed medication for the underlying condition is
the cause of the positive urine screen.

28. A prolonged QT/QTc interval (QTc Fridericia [QTcF] >480 ms) demonstrated on the ECG
at Screening or Baseline. A history of risk factors for torsade de pointes (eg, heart
failure, hypokalemia, family history of long QT Syndrome).

29. Currently enrolled in another clinical study or used any investigational drug or
device within 28 days or 5× the half-life of the investigational drug, whichever is
longer, preceding informed consent.

30. Intake of nutritional supplements, juice, and herbal preparations or other foods or
beverages that may affect the various drug metabolizing enzymes and transporters (eg,
alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or
orange juice, vegetables from the mustard green family [eg, kale, broccoli,
watercress, collard greens, kohlrabi, brussel sprouts, mustard], and charbroiled
meats) within 1 week before dosing.

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

32. Engagement in strenuous exercise within 2 weeks before Baseline.

For Healthy Participants (Cohorts 1C and 2C)

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

34. Evidence of disease that may influence the outcome of the study within 4 weeks before
dosing; eg, psychiatric disorders and disorders of the gastrointestinal tract, liver,
kidney, respiratory system, endocrine system, hematological system, neurological
system, or cardiovascular system), or participants who have a congenital abnormality
in metabolism. Participants with history of seizures in adulthood are excluded.

35. Any history of gastrointestinal surgery that may affect the drug absorption (eg,
hepatectomy, nephrotomy, digestive organ resection, but not cholecystectomy) at
Screening.

36. Any clinically abnormal symptom or organ impairment found by medical history at
Screening, and physical examinations, vital sign assessments, ECG finding, or
laboratory test results that require medical treatment at Screening.

37. A prolonged QT/QTc interval (QTcF >450 ms) demonstrated on ECG at Screening or
Baseline. A history of risk factors for torsade de pointes (eg, heart failure,
hypokalemia, family history of long QT Syndrome), or the use of concomitant
medications that prolonged the QT/QTc interval.

38. Known history of clinically significant drug allergy at Screening.

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

40. Known to be HIV-positive at Screening.

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

42. History of drug or alcohol dependency or abuse within the 1 year before Screening, or
those who have a positive urine drug test or breath (or urine) alcohol test at
Screening or Baseline.

43. Intake of nutritional supplements, juice, and herbal preparations or other foods or
beverages that may affect the various drug metabolizing enzymes and transporters (eg,
alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or
orange juice, vegetables from the mustard green family [eg, kale, broccoli,
watercress, collard greens, kohlrabi, brussel sprouts, mustard], and charbroiled
meats) within 1 week before dosing.

44. Intake of herbal preparations containing St. John's wort within 4 weeks before
dosing.

45. Use of prescription drugs except those allowed per the inclusion/exclusion criteria
(eg, contraception) within 4 weeks or 5 half-lives, whichever is longer, before
dosing.

46. Intake of over-the-counter (OTC) medications within 2 weeks or 5 half-lives,
whichever is longer, before dosing.

47. Currently enrolled in another clinical study or used any investigational drug or
device within 28 days or 5x the half-life of the investigational drug, whichever is
longer, preceding informed consent.

48. Receipt of blood or blood products within 4 weeks, or donation of blood within 4
weeks, of dosing.

49. Engagement in strenuous exercise within 2 weeks before Baseline.