Eligibility Details:
Inclusion Criteria:
All subjects:
1. Provision of signed and dated informed consent form (ICF)
2. Stated willingness to comply with all study procedures and availability for the
duration of the study
3. If female, meets 1 of the following criteria:
1. Is of childbearing potential and agrees to use an accepted contraceptive method.
Acceptable method of contraception include:
- Abstinence from heterosexual intercourse from at least 28 days prior to the
first study drug administration through to at least 30 days after the last
dose of the study drug or until completion of the study, whichever is longer
- Male partner vasectomized at least 6 months prior to the first study drug
administration
- Use a systemic contraceptive or an intrauterine device (with or without
hormones), from at least 28 days prior to the first study drug
administration through to at least 30 days after the last dose of the study
drug or until completion of the study, whichever is longer, with a male
condom or a diaphragm/cervical cap plus spermicide, from the first study
drug administration through to at least 30 days after the last dose of the
study drug or until completion of the study, whichever is longer Or
2. Male partner has had a vasectomy less than 6 months prior to dosing, and agrees
to use an additional acceptable contraceptive method from the first study drug
administration through to at least 30 days after the last dose of the study drug
or until completion of the study, whichever is longer Or
3. Is of non-childbearing potential, defined as surgically sterile (i.e. has
undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is
in a postmenopausal state (i.e. at least 1 year without menses without an
alternative medical condition prior to the first study drug administration and
follicle-stimulating hormone levels ≥ 40 mIU/mL at screening)
4. If male, meets 1 of the following criteria:
1. Is able to procreate and agrees to use 1 of the accepted contraceptive regimens
and not to donate sperm from the first study drug administration to at least 90
days after the last drug administration. An acceptable method of contraception
includes 1 of the following:
- Abstinence from heterosexual intercourse
- Male condom with spermicide or male condom with a vaginal spermicide (gel,
foam, or suppository) or
2. Is unable to procreate; defined as surgically sterile (i.e. has undergone a
vasectomy at least 180 days prior to the first study drug administration)
5. Light-, non- or ex-smoker (A light-smoker is defined as someone using 10.0 nicotine
units or less per day for at least 90 days prior to the first study drug
administration. An ex smoker is defined as someone who completely stopped using
nicotine products for at least 180 days prior to the first study drug administration)
6. Clinical laboratory values within the laboratory's stated normal range; if not within
this range, they must be without clinical significance, as determined by an
investigator
7. Have no clinically significant diseases captured in the medical history or evidence of
clinically significant findings on the physical examination (including vital signs)
and/or ECG, as determined by an investigator
Healthy subjects (Phase 1a):
8. Male or female, aged at least 18 years but not older than 55 years
9. Body mass index (BMI) within 18.0 kg/m2 to 32.0 kg/m2, inclusive
HBV-infected subjects (Phase 1b):
10. Male or female, aged at least 18 years but not older than 65 years
11. BMI within 18.0 kg/m2 to 35.0 kg/m2, inclusive
12. Serum HBsAg positive at screening and at least 6 months prior to screening
13. Serum HBeAg positive and HBV DNA ≥ 20,000 IU/mL, or serum HBeAg negative and HBV DNA ≥
2,000 IU /mL at screening
14. ALT and AST <5 times the upper limit of normal (ULN) at screening and prior to the
first study drug administration
Exclusion Criteria:
All subjects:
1. Female who is lactating at screening
2. Female who is pregnant according to the pregnancy test at screening or prior to the
first study drug administration
3. History of significant hypersensitivity to clevudine or any related products
(including excipients of the formulations) as well as severe hypersensitivity
reactions (like angioedema) to any drugs
4. History of significant cardiovascular, pulmonary, hematologic, neurological,
psychiatric, endocrine, immunologic or dermatologic disease
5. Presence of clinically significant muscle disorders, myopathies or other forms of
liver disease
6. Presence of clinically significant ECG abnormalities at the screening visit, as
defined by medical judgment
7. Positive test result for alcohol and/or drugs of abuse at screening or prior to the
first drug administration
8. Any history of tuberculosis
9. Inclusion in a previous cohort for this clinical study
10. Intake of an Investigational Product (IP) in the 28 days prior to the first study drug
administration
11. Active illicit drug use including, but not limited to, cocaine, heroin and
methamphetamine (the use of cannabinoid is acceptable)
12. Donation of 50 mL or more of blood in the 28 days prior to the first study drug
administration
13. Donation of 500 mL or more of blood in the 56 days prior to the first study drug
administration
Healthy subjects (Phase 1a):
14. Maintenance therapy with any drug or significant history of drug dependency or alcohol
abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
15. Any clinically significant illness in the 28 days prior to the first study drug
administration
16. Presence or history of clinically significant gastrointestinal, liver or kidney
disease, or surgery that may affect drug bioavailability
17. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or
hepatitis C virus tests
18. Use of any prescription drugs including amiodarone (with the exception of hormone
replacement therapy) in the 28 days prior to the first study drug administration, that
in the opinion of an investigator would put into question the status of the
participant as healthy
HBV-infected subjects (Phase 1b):
19. Significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day,
intake of excessive alcohol, acute or chronic)
20. Use of amiodarone in the 28 days prior to the first study drug administration
21. Presence or history of clinically significant gastrointestinal or kidney disease, or
surgery that may affect drug bioavailability
22. Cirrhosis of the liver as determined by one of the following:
- A score greater than F2 for liver fibrosis by FibroScan or FibroSure test within
6 months prior to screening or at the time of screening OR
- A score greater than F2 on liver biopsy within 12 months prior to screening or at
the time of screening
23. Medical history or known presence of hepatocellular carcinoma
24. Previous treatment for hepatitis B virus, including nucleoside therapy
25. Acute infection or any other clinically significant illness within 14 days of
randomization
26. History of organ transplantation
27. Uncontrolled hypertension
28. Positive screening results to HIV Ag/Ab combo, hepatitis C virus or hepatitis D virus
tests
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
