| Eligibility |
Inclusion Criteria:
1. The subject is male or female between the ages of 18 and 55 years old (inclusive) at
the time of informed consent.
2. The subject has a body mass index (BMI) >18 and =29 kg/m2 at screening.
3. Female subjects must be of non-childbearing potential (eg, postmenopausal [defined as
cessation of all menstrual periods for at least 1 year without an alternative medical
cause, and confirmed by follicle-stimulating hormone (FSH) test =40 IU/L] or
surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal
ligation).
4. Male subjects with partners of childbearing potential must always use a condom and
must agree in addition to use a highly effective form(s) of contraception, that
results in a low failure rate (<1% per year) when used consistently and correctly,
starting during the screening period, continuing throughout the entire study period,
and for 90 days after taking the last dose of study drug. Such methods include:
1. Oral hormonal contraception (combined estrogen/progestogen, or progestogen-only)
associated with inhibition of ovulation
2. Intrauterine device (IUD)
3. Intrauterine hormone-releasing system (IUS)
4. Bilateral tubal ligation
5. Vasectomy
6. True sexual abstinence in line with the preferred and usual lifestyle of the
subject.
Highly effective contraception should always be combined with an additional barrier
method (eg, diaphragm, with a spermicide).
5. The subject must provide written informed consent prior to any study-specific
screening procedures.
6. The subject is willing and able to comply with all aspects of the protocol, as
determined by the Investigator.
Exclusion Criteria:
1. Clinical laboratory test results from the coagulation panel (international normalized
ratio [INR], prothrombin time, and activated partial thromboplastin time) must be
within the normal laboratory reference ranges or deemed not clinically significant by
the Investigator and Sponsor.
2. The subject has clinically significant renal laboratory findings, including estimated
glomerular filtration rate <80 mL/min as calculated by the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation.
3. The subject has a known history of any gastrointestinal surgery or any condition
possibly affecting drug absorption (eg, cholecystectomy, gastrectomy, achlorhydria,
peptic ulcer disease, history of stomach or intestinal surgery or resection).
Appendectomy and hernia repair are allowed.
4. The subject had a clinically significant illness within 8 weeks or a clinically
significant infection within 4 weeks prior to the first dose.
5. The subject has evidence of a clinically significant deviation from normal in the
physical examination, vital signs, or clinical laboratory determinations at screening
or at Day -1 check-in (baseline).
6. The subject has systolic blood pressure >140 mmHg or diastolic blood pressure >90
mmHg.
7. The subject has a clinically significant ECG abnormality, including a marked baseline
prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval >480
msec), or had a family history of prolonged QTc syndrome or sudden death.
8. The subject has a history of smoking or use of nicotine-containing substances within
the previous 2 months, as determined by medical history or subject's verbal report and
confirmed by cotinine test at check in for each treatment period.
9. The subject has a history of drug or alcohol misuse within 6 months prior to screening
or a positive urine drug test at screening or at check in for each treatment period.
10. The subject has been diagnosed with acquired immune deficiency syndrome (AIDS) or has
performed tests that are positive for human immunodeficiency virus (HIV), hepatitis B
virus (HBV), or hepatitis C virus (HCV).
11. The subject has participated in a clinical trial of other drug before screening, and
the time since the last use of other study drug is less than 5 times the half-life or
4 weeks, whichever is longer, or the subject is currently enrolled in another clinical
trial.
12. The subject has consumed grapefruit, starfruit, Seville oranges, or their products
within 7 days prior to the first dose.
13. The subject has consumed herbal preparations/medications, including, but not limited
to, kava, ephedra (ma huang), Ginkgo biloba, dehydroepiandrosterone (DHEA), yohimbe,
saw palmetto, and ginseng, within 7 days prior to the first dose.
14. The subject has experienced a weight loss or gain of >10% within 4 weeks prior to the
first dose as noted by medical history and weight at screening and check-in.
15. The subject has received blood or blood products within 4 weeks, or donated blood or
blood products within 8 weeks prior to the first dose or donated double red cell
within 16 weeks prior to first dose.
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Page 32 CONFIDENTIAL
16. The subject has used any over-the-counter (OTC) medications or prescription drugs that
can affect gastric acid (proton pump inhibitors [PPIs], H2 blockers or locally acting
antacids) or that inhibit CYP3A, P-gp, or BCRP in particular, within 2 weeks prior to
the first dose.
17. Subject has used CYP3A inducers (including St John's wort) within 30 days before the
first dose.
18. The subject is allergic to any of the study drugs (or its excipients) to be given in
this study.
19. Female participant is pregnant, lactating, or breastfeeding.
20. Male subject who plans to donate sperm or father a child within 3 months after
receiving the study drug.
21. The subject has any condition that would make him or her, in the opinion of the
Investigator or Sponsor, unsuitable for the study, or who, in the opinion of the
Investigator, is not likely to complete the study for any reason.
One repeat of laboratory assessments may be performed at screening and check in at the
discretion of the Investigator.
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