| Eligibility |
Inclusion Criteria:
All subjects
- The subject is male or female between the ages of 18 and 79 years old (inclusive).
- The subject has a BMI >18 and =40 kg/m2 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 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 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
treatment period and for 90 days after study drug discontinuation. Males must confirm
that female partners of childbearing potential agree to use medically accepted
contraception methods.
Subjects with Moderate Renal Impairment
- The subject must have eGFR of 30-59 mL/min/1.73 m^2 as calculated by MDRD.
- 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
- 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 Renal Function
- The subject must be without renal disease and have normal renal function (eGFR =90
mL/min/1.73 m2 based on the MDRD equation) at screening and check-in. Clinical
laboratory test results must be within the normal laboratory reference ranges for
serum urea, serum protein, and serum albumin.
- The subject must be without renal disease and have normal renal 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, hepatic, GI,
respiratory, endocrine, hematological, neurological, or psychiatric disease or
abnormalities.
- 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), Hepatitis B virus (HBV), or
Hepatitis C virus (HCV).
- 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 experienced a weight loss or gain of >10% within 4 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 Moderate Renal Impairment
- The subject has clinically significant vital sign abnormalities at screening or
baseline.
- 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 clinically significant physical, laboratory, or ECG findings
- The subject has any history of renal transplant.
- The subject has any known significant bleeding diathesis (eg, history of recent
bleeding from esophageal varices) that could preclude multiple venipuncture or deep
intramuscular injections.
- The subject has acute or exacerbating renal disease, fluctuating or rapidly
deteriorating renal function as indicated by widely varying or worsening of clinical
and/or laboratory signs of renal impairment within 2 weeks of first dose.
Subjects with Normal Renal Function
- The subject has evidence of clinically significant renal disease 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 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 nonprescription drugs, including
over-the-counter (OTC) medications or vitamins, within 2 weeks prior to the first
dose.
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