| Eligibility |
Inclusion Criteria:
1. Healthy, adult, male or female (of non childbearing potential only) 19 55 years of
age, inclusive, at screening.
2. Continuous non smoker who has not used nicotine containing products for at least 3
months prior to (the first) dosing and throughout the study, based on subject self
reporting.
3. Body mass index (BMI) = 18 and = 32.0 kg/m2 at screening.
4. Medically healthy with no clinically significant medical history, physical
examination, neurological examination, ophthalmic examination, laboratory profiles,
vital signs or ECGs, as deemed by the PI or designee.
5. A female subject must be of non childbearing potential and must have undergone one of
the following sterilization procedures at least 6 months prior to (the first) dosing:
- hysteroscopic sterilization;
- bilateral tubal ligation or bilateral salpingectomy;
- hysterectomy;
- bilateral oophorectomy; or
- be postmenopausal with amenorrhea for at least 1 year prior to (the first) dosing
and follicle stimulating hormone (FSH) serum levels consistent with
postmenopausal status.
6. A non vasectomized, male subject must agree to use a condom with spermicide or abstain
from sexual intercourse during the study until 90 days after (the last) dosing. (No
restrictions are required for a vasectomized male provided his vasectomy has been
performed 4 months or more prior to (the first) dosing of study drug. A male who has
been vasectomized less than 4 months prior to study (first) dosing must follow the
same restrictions as a non vasectomized male).
7. If male, must agree not to donate sperm from the first dosing until 90 days after (the
last) dosing.
8. Able to swallow multiple capsules.
9. Understands the study procedures in the informed consent form (ICF), and be willing
and able to comply with the protocol.
Exclusion Criteria:
- 1. Is mentally or legally incapacitated or has significant emotional problems at the
time of the screening visit or expected during the conduct of the study.
2. History or presence of clinically significant medical or psychiatric condition or
disease in the opinion of the PI or designee.
3. History of any illness that, in the opinion of the PI or designee, might confound
the results of the study or poses an additional risk to the subject by their
participation in the study.
4. Is at suicidal risk in the opinion of the PI as per the following criteria:
1. Any suicide attempts within 12 months prior to screening or any suicidal intent,
including a plan, within 3 months prior to screening.
2. C-SSRS answer of "YES" on suicidal ideation within 3 months prior to screening.
5. History or presence of alcoholism or drug abuse within the past 2 years prior
to (the first) dosing.
6. History or presence of hypersensitivity or idiosyncratic reaction to the study
drug or related compounds.
7. History of allergy to lignocaine/fluorescein (LF) or tropicamide (T) (eye
examination agents).
8. History of seizures (childhood febrile seizures are excepted). 9. Female
subjects of childbearing potential. 10. Female subjects with a positive pregnancy
test or who are lactating. 11. Positive urine drug or alcohol results at
screening or check in. 12. Positive results at screening for human
immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C
virus (HCV).
13. Supine blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at
screening.
14. Supine heart rate is lower than 40 bpm or higher than 99 bpm at screening.
15. Estimated creatinine clearance <90 mL/min at screening. 16. Unable to refrain
from or anticipates the use of any drug including prescription and non
prescription medications, herbal remedies, or vitamin supplements beginning 14
days prior to the first dosing and throughout the study. Drugs known to be
significant inducers of cytochrome P450 (CYP) enzymes and/or P-glycoprotein (P
gp), including St. John's Wort will be prohibited for 28 days prior to the first
dosing and throughout the study. After dosing, acetaminophen (up to 2 g per 24
hours) may be administered at the discretion of the PI or designee. For subjects
having CSF sampling, topical medication for minor dermatological conditions,
stool softeners, local anesthetics, and/or intravenous normal saline may be
permitted as appropriate for lumbar puncture procedure for CSF sample collection
at the discretion of the PI.
17. Has been on a diet incompatible with the on study diet, in the opinion of the
PI or designee, within the 30 days prior to (the first) dosing and throughout the
study.
18. Donation of blood or significant blood loss within 56 days prior to (the
first) dosing.
19. Plasma donation within 7 days prior to (the first) dosing. 20. Participation
in another clinical study within 30 days prior to the (first) dosing. The 30 day
window will be derived from the date of the last blood collection or dosing,
whichever is later, in the previous study to Day 1 (of Period 1 for the Fed
Cohort) of the current study.
21. History or presence of: risk factors for Torsade de Pointes (e.g., heart
failure, cardiomyopathy, or family history of Long QT Syndrome); sick sinus
syndrome, second or third degree atrioventricular block, myocardial infarction,
pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged
QTcF interval, or conduction abnormalities.
22. Has an abnormal screening ECG indicating a second- or third- degree AV block,
or one or more of the following: QRS > 120 msec, QTcF > 450 msec for males and >
460 msec for females, PR interval > 220 msec. Any rhythm other than normal sinus
rhythm, which is interpreted by the PI or designee to be clinically significant
at screening or check-in.
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