A 2-Part Study to Assess Potential Metabolism-Based Drug-Drug Interactions of E2006 When Coadministered With Itraconazole, Rifampin, Midazolam, or Bupropion

Inclusion Criteria

Subjects must meet all of the following criteria to be included in this study:

1. Healthy males or females, ages 18 to 55 years

2. Body mass index greater than 18 and less than or equal to 32 kg/m2 at Screening

3. All females must be of nonchildbearing potential

4. Males who are not abstinent or have undergone a successful vasectomy, who are
partners of women of childbearing potential must use, or their partners must use, a
highly effective method of contraception

5. Are willing and able to comply with all aspects of the protocol

6. Provide written informed consent

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

1. Any subject that has a known history of malaria or has traveled to a country with
known malarial risk (ie, is designated as "high" or "moderate" risk country according
to the list available at http://www.cdc.gov/malaria) within the last year

2. Subjects with a history of bowel resection, any malabsorptive disorder, severe
gastroparesis, or any gastrointestinal procedure for the purpose of weight loss
(including LAP-BANDTM), which would slow gastric emptying and potentially affect PK
profiles of E2006

3. Subjects with a known history of clinically significant drug or food allergies

4. Subjects who experienced a weight loss or gain of greater than 10% between Screening
and prior to dosing

5. Subjects who had a clinically significant illness that required medical treatment
within 8 weeks or a clinically significant infection within 4 weeks of dosing

6. Subjects with any clinically abnormal symptom or organ impairment found in medical
history, symptoms or signs, vital sign measurements, electrocardiogram (ECG)
findings, or laboratory test results that require medical treatment found in medical
history or at screening and baseline

7. Subjects known to be positive for human immunodeficiency virus, or subjects who have
positive hepatitis B or hepatitis C screening test results

8. Subjects who have a history of drug or alcohol dependency or abuse (as defined by The
Diagnostic and Statistical Manual of Mental Disorders V criteria) within
approximately 2 years prior to Screening, or who have a positive urine drug test
results at Screening or Baseline

9. Subjects who received blood products within 4 weeks, donated blood within 8 weeks, or
donated plasma within 1 week of dosing

10. Subjects who used hormonal replacement therapy within 3 months prior to dosing

11. Subjects who used any drugs, over-the-counter (OTC) medications, nutritional
supplements (eg, products containing St John's wort), excessive doses of vitamins (in
the opinion of the principal investigator), herbal preparations, or foods or
beverages known to modulate CYP (eg, CYP3A4) or transporters within 4 weeks prior to
dosing, or who are unwilling to abstain from using these during the study

12. Subjects who engaged in intense physical activity within 1 week prior to Baseline
(eg, weight training)

13. Subjects who smoke or have used tobacco or nicotine-containing products within 3
months prior to dosing

14. Subjects who habitually consume more than 400-mg caffeine per day

15. Subjects who participated (received investigational product) in another clinical
trial less than 1 month (or 5 elimination half-lives of the investigational product)
prior to dosing or who are currently enrolled in another clinical trial

16. Subjects with a disease that may influence the outcome of the study, such as
psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney,
respiratory system, endocrine system, hematological system, neurological system, or
cardiovascular system, or subjects who have a congenital abnormality in metabolism,
or subjects who have any condition that would make him or her, in the opinion of the
investigator, unsuitable for the study or who, in the opinion of the investigator,
are not likely to complete the study for any reason

Restrictions on concomitant medications, food and beverages:

17. Prescription drugs are prohibited within 4 weeks of dosing and OTC medications within
2 weeks prior to dosing and until the Termination Visit

18. Smoking or use of tobacco or nicotine-containing products is prohibited within 4
weeks prior to dosing and until Termination Visit

19. Intake of caffeinated beverages or food is prohibited 72 hours prior to dosing and
throughout the entire study

20. 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, Brussels sprouts, mustard] and charbroiled
meats) is prohibited within 2 weeks prior to dosing until the Termination Visit