| Eligibility |
Inclusion Criteria:
1. Able to comprehend and willing to sign an informed consent form (ICF);
2. Male or female subjects, between 18 and 65 years of age, inclusive;
3. Within body mass index (BMI) range 18 to 40 kg/m2, inclusive;
4. Negative test for selected drugs of abuse at Screening (does not include alcohol) and
at Check-in (does include alcohol); positive drug screens in the hepatically-impaired
subjects may be allowed with the confirmation of use of the medication under
supervision of a physician)
5. Negative HIV antibody and hepatitis B surface antigen (HBsAg) screens;
6. Female subjects will be non-pregnant, non-lactating, and either postmenopausal for at
least 1 year (with follicle-stimulating hormone (FSH) levels =40 mIU/mL), surgically
sterile (e.g., tubal ligation, hysterectomy) for at least 90 days, or agree to use
from the time of signing the ICF until 30 days after Study Discharge one of the
following forms of contraception: a non-hormonal intrauterine device (IUD) with
spermicide; female condom with spermicide; contraceptive sponge with spermicide; a
non-hormonal intravaginal system; diaphragm with spermicide; cervical cap with
spermicide; a male sexual partner who agrees to use a male condom with spermicide; or
a sterile sexual partner; for all female subjects, the pregnancy test result must be
negative at Screening and Check-in;
7. Male subjects will either be sterile or agree to use from Check-in until 45 days
following Study Discharge one of the following approved methods of contraception: a
male condom with spermicide; a sterile sexual partner; or use by female sexual partner
of an IUD with spermicide; a female condom with spermicide; contraceptive sponge with
spermicide; an intravaginal system (e.g., NuvaRing®); a diaphragm with spermicide; a
cervical cap with spermicide; or oral, implantable, transdermal, or injectable
contraceptives.
For healthy subjects with normal hepatic function:
1. Normal hepatic function defined as alanine aminotransferase, aspartate
aminotransferase, bilirubin, serum albumin, and gamma glutamyl transferase all within
normal limits;
2. The absence of clinically-relevant abnormalities identified by a detailed medical
history, full physical examination, vital signs, 12-lead electrocardiogram (ECG), and
clinical laboratory tests;
3. Negative hepatitis panel (including HBsAg and hepatitis C virus antibody);
4. No medical or surgical conditions that might significantly interfere with
gastrointestinal absorption of CMX001.
For subjects with impaired hepatic function:
1. Otherwise healthy subjects as determined by a detailed medical history, complete
physical examination, vital signs, 12-lead ECG, and clinical laboratory tests
(abnormal findings that are related to the subject's underlying condition are
acceptable);
2. Satisfy the criteria for Class B or Class C of the modified Child-Turcotte-Pugh (CPT)
classification (mild [CPT score of 5 to 6 points], moderate [CPT score of 7 to 9
points], and severe [CPT score of >9 to <12 points]);
3. A diagnosis of chronic hepatic impairment due to cirrhosis or fibrosis, not secondary
to other diseases, which is confirmed and documented by medical history, physical
examination, and/or liver biopsy, hepatic ultrasound, computed tomography scan, or
magnetic resonance imaging.
Exclusion Criteria:
1. Significant history or clinical manifestation of any significant metabolic, allergic,
dermatological, hepatic (healthy control subjects only), renal, hematological,
pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as
determined by the Investigator, Sponsor, and/or Sponsor's representative);
2. Any non-hepatic disease or condition that could affect safety or data interpretation
(as determined by the Investigator, Sponsor, and/or Sponsor's representative);
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound,
including cidofovir (CDV), food, or other substance, unless approved by the
Investigator, Sponsor, and/or Sponsor's representative;
4. History of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs except that appendectomy
and/or hernia repair will be allowed;
5. History of any condition possibly affecting drug absorption (e.g., gastrectomy, active
peptic ulcer) within the last 3 months;
6. serum albumin <3 g/dL;
7. History or presence of an abnormal ECG, which, in the opinion of the Investigator,
Sponsor, and/or Sponsor's representative, is clinically significant;
8. History of alcoholism or drug addiction within 1 year prior to Check-in (healthy
control subjects only);
9. Use of any tobacco- or nicotine-containing products within 6 months prior to Check-in
(healthy control subjects only);
10. Participation in any other investigational study drug trial in which receipt of an
investigational study drug occurred within 30 days (or 5 half-lives, whichever is
longer) prior to Check-in;
11. Use of oral, implantable, injectable, or transdermal contraceptives within 14 days
prior to Check-in (female subjects only);
12. For healthy control subjects, use of any prescription medications/products within 14
days prior to Check-in, unless deemed acceptable by the Investigator and Sponsor;
13. For healthy control subjects, use of any over-the-counter (OTC), non-prescription
preparations (including vitamins, minerals, and phytotherapeutic/ herbal/plant-derived
preparations) within 7 days prior to Check-in, unless deemed acceptable by the
Investigator, Sponsor, and/or Sponsor's representative;
14. Use of alcohol-, grapefruit-, or caffeine-containing foods or beverages within 72
hours prior to Check-in, unless deemed acceptable by the Investigator, Sponsor, and/or
Sponsor's representative;
15. Poor peripheral venous access;
16. Donation of blood during the period of 30 days prior to Screening or donation of
plasma during the period of 2 weeks prior to Screening;
17. Receipt of blood products within 2 months prior to Check-in;
18. Any acute or chronic non-hepatic condition that, in the opinion of the Investigator,
Sponsor, and/or Sponsor's representative, would limit the subject's ability to
complete and/or participate in this clinical study;
19. History of liver transplant;
20. History of febrile illness within 5 days prior to dosing.
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