| Eligibility |
Inclusion Criteria:
All Subjects
- Male or female between 18 and 75 (inclusive)
- Subject has BMI >18 and =40 kg/m^2 and body weight not =50 kg at screening.
- The subject is a non-smoker or light smoker who smokes no more than 10 cigarettes, 2
cigars, 2 pipes, or other nicotine equivalents (eg, vape, snuff, gum) of tobacco per
day; willing to limit smoking during the treatment period to 4 cigarettes or 1 cigar
per day.
- Females of non-childbearing potential or surgically sterile
- Males who have not had a successful vasectomy and are partners of women of
childbearing potential must use, or their partners must use, a medically acceptable
method of contraception starting for at least 1 menstrual cycle prior to and
throughout the entire study period, and for 2 weeks after the last dose of study drug.
Those with partners using hormonal contraceptives must also use an additional approved
method of contraception such as a condom with spermicide. Males who have had a
successful vasectomy (confirmed azoospermia, documentation needed) require no
additional contraception. No sperm donation is allowed during the study period and for
90 days after study drug discontinuation.
Subjects with Hepatic Impairment
- For moderate hepatic impairment, the subject must have a Child-Pugh score of 7 to 9.
For mild hepatic impairment, the subject must have a Child-Pugh score of 5 to 6.
- The subject must have no clinically significant change in disease status within the
last 30 days before screening.
- If diabetic, the subject must have the disease controlled
- Subjects with ascites must not have a paracentesis within 3 months of screening.
- The subject must have blood pressure between 90 and 160 mm Hg systolic, inclusive, and
not higher than 100 mm Hg diastolic.
Subjects with Normal Hepatic Function
- The subject must be without hepatic disease and have normal hepatic function
- The subject must be in good health
- The subject must have blood pressure between 95 and 150 mm Hg systolic, inclusive, and
no higher than 90 mm Hg diastolic
Exclusion Criteria:
All Subjects
- The subject has evidence of clinically significant cardiovascular, GI, renal,
respiratory, endocrine, hematological, neurological, or psychiatric disease or
abnormalities.
- The subject has a known history of any GI surgery or any condition possibly affecting
drug absorption.
- The subject has a clinically significant illness within 8 weeks or a clinically
significant infection within 4 weeks prior to the first dose.
- The subject has a clinically significant ECG abnormality
- The subject has been diagnosed with acquired immune deficiency syndrome (AIDS), or
tests positive for human immunodeficiency virus (HIV).
- The subject has participated in a clinical study of another drug before dosing, and
the time since the last use of other study drug is less than 5 times the half-life or
4 weeks before Day 1, whichever is longer, or is currently enrolled in another
clinical study.
- The subject has consumed grapefruit, starfruit, Seville oranges, or their products
within 7 days prior to the first dose.
- 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.
- The subject has received blood or blood products within 8 weeks, or donated blood or
blood products within 8 weeks prior to the first dose, or donated double red cells
within 16 weeks prior to the first dose.
- The subject has used any drug that is a strong inhibitor or inducer (including St.
John's wort) of CYP3A or P-gp within 2 weeks prior to first dose or will require use
during study treatment period.
- The subject is allergic to the study drug or to any of its excipients.
- Female subjects who are pregnant or planning to become pregnant, lactating, or
breastfeeding.
- The subject has used a proton pump inhibitor (PPI) within 4 days prior to the first
dose or a histamine 2 (H2) receptor antagonist (H2 blocker) within 2 days prior to the
first dose.
Subjects with Hepatic Impairment
- The subject has clinically significant vital sign abnormalities at screening or
baseline.
- The subject has used acetaminophen at doses >1 g/day within 2 weeks prior to study
drug administration.
- The subject has a history or current diagnosis of uncontrolled or significant cardiac
disease indicating significant risk of safety for participation in the study
- The subject has Gilbert's syndrome, liver transplant, Wilson's disease, autoimmune
liver disease
- The subject has previously been diagnosed with hepatocellular carcinoma.
- The subject has acute or exacerbating hepatitis, fluctuating or rapidly deteriorating
hepatic function
- The subject has a history of drug misuse within 6 months prior to screening or a
positive drug test at screening or on Day -1.
- The subject has evidence of current or recent abuse of alcohol
- The subject has received therapy known to exacerbate hepatic impairment within 4 weeks
of study drug administration.
- The subject is taking antiviral therapy for treatment of active hepatitis infection at
the time of screening.
Subjects with Normal Hepatic Function
- The subject has evidence of clinically significant hepatic illness or abnormalities.
- The subject has evidence of a clinically significant deviation from normal in the
physical examination, vital signs, or clinical laboratory determinations at screening
or baseline.
- The subject tests positive for Hepatitis B virus (HBV), HBsAg, Hepatitis C virus
(HCV), or Hepatitis C antibody
- The subject has used any prescription or nonprescription drugs, including
over-the-counter (OTC) medications or vitamins, within 2 weeks prior to the first
dose, unless otherwise specified.
- The subject has a history of drug or alcohol misuse within 6 months prior to screening
or a positive drug test at screening or on Day -1.
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