| Eligibility |
Inclusion Criteria:
All Subjects
- Male or female between the ages of 18 and 75 years old (inclusive)
- BMI >18 and =40 kg/m2 and body weight not <50 kg at screening.
- 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 must be 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 treatment phase, 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.
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 clinical condition within
the last 30 days before screening
- The subject must have a condition consistent with hepatic impairment and associated
symptoms but otherwise be determined to be in good health in the opinion of the
Investigator.
- Subjects with ascites must not have a paracentesis within 3 months of screening.
- If diabetic, the subject must have the diabetes controlled (as determined by the
Investigator).
- Concomitant medications to treat underlying disease states or medical conditions
related to hepatic impairment are allowed. Subjects must be on a stable dose of
medication and/or treatment regimen for at least 2 weeks before dosing as well as
during the study.
Subjects with Normal Hepatic Function
- The subject must be without hepatic disease and have normal hepatic function
- The subject must be in good health
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 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 clinically significant renal laboratory findings, including estimated
creatinine clearance <60 mL/min as calculated by the Cockcroft-Gault equation.
- The subject has participated in a clinical study of another 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 before day 1
- The subject has consumed grapefruit, starfruit, Seville oranges, or their products
within 7 days prior to day 1.
- 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 day 1.
- The subject has received blood or blood products within 8 weeks, or donated blood or
blood products within 8 weeks prior to day 1 or donated double red cells within 16
weeks prior to day 1.
- The subject has experienced a weight loss or gain of >10% within 4 weeks prior to day
1 as documented by recent medical history and weight at screening to check-in
(excluding subjects with moderate hepatic impairment).
- The subject has used any drug that is a strong inhibitor or inducer of CYP3A within 2
weeks (within 3 weeks for St. John's wort) prior to day 1 or will require use during
the treatment period.
- The subject is allergic to the study drug or to any of its excipients.
- Female subject who is pregnant or planning to become pregnant, lactating, or
breastfeeding.
- Male subject who plans to donate sperm or father a child within 3 months after
receiving the study drug.
Subjects with Hepatic Impairment
- The subject has clinically significant vital sign abnormalities at screening or day -1
- 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, esophageal variceal bleeding within 3 months prior to screening unless
successfully treated with banding, known gastric varices, spontaneous bacterial
peritonitis or paracentesis within 3 months before screening, cholestatic liver
disease (eg, primary biliary cirrhosis or primary sclerosing cholangitis), history of
biliary sepsis within the past 2 years, or a portosystemic shunt.
- The subject has previously diagnosed with hepatocellular carcinoma.
- The subject has acute or exacerbating hepatitis, fluctuating hepatic function, or
rapidly deteriorating hepatic function as indicated by widely varying or worsening of
clinical and/or laboratory signs of hepatic impairment in the judgment of either the
Investigator or the Sponsor's medical monitor.
- 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. A positive drug test may not be
exclusionary if it is deemed to be the result of an approved prescribed concomitant
medication.
- The subject has evidence of current or recent abuse of alcohol, which, in the
Investigator's opinion, would compromise subject's safety or compliance with the study
procedures or positive alcohol test at screening or on day -1
- The subject has received therapy known to exacerbate hepatic impairment within 2 weeks
of day 1.
- The subject is taking antiviral therapy for treatment of active hepatitis infection at
the time of screening.
- The subject has presence of clinically significant laboratory findings at screening
are exclusionary, particularly:
- Hemoglobin <8.5 g/dL
- Platelet count <25,000/mm3
- ALT or AST >5× upper limit of normal (ULN)
- Hepatitis B surface antigen (HBsAg) positive and/or Hepatitis B core antibody
positive
- The subject has systolic blood pressure >160 mmHg or diastolic blood pressure >100
mmHg at screening or day -1
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 day -1
- The subject tests positive for Hepatitis B virus (HBV) assessed by the HBsAg and/or
Hepatitis B core antibody, Hepatitis C virus (HCV), or Hepatitis C antibody.
- The subject has a history of drug or alcohol misuse within 6 months prior to screening
or a positive drug test at screening or day -1
- The subject has used any prescription or non-prescription drugs, including
over-the-counter (OTC) medications or vitamins, within 2 weeks prior to day
- The subject has systolic blood pressure >150 mmHg or diastolic blood pressure >95 mmHg
at screening or day -1
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