None listed
Conditions
Brief summary
This is a randomized, open-label, active-controlled study whose primary objective is to evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the safety, viral kinetics, and antiviral activity of each of four doses of GS-7340 over 28 days of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of GS-7340 versus TDF 300-mg over 28 days of therapy. Approximately 50 eligible subjects with chronic HBV infection who are naïve to anti-HBV treatment will be randomized 1:1:1:1:1 to receive treatment with GS-7340 8-, 25-, 40-, or 120-mg or TDF 300-mg orally once daily. Subjects may be HBeAg+ or HBeAg-. Enrollment will be stratified by HBeAg status with approximately a 1:1 distribution resulting in approximately 25 HBeAg+ and 25 HBeAg- subjects. All subjects must be followed for safety for 30 days after the 28-day treatment. Optional blood samples may be obtained for exploratory biomarker and pharmacogenomic discovery research at any time during the study or at a separate post study visit, if necessary. Subjects who agree to have blood drawn for pharmacogenomic research will sign a separate informed consent form.
Interventions
4 different doses of GS-7340 (8-mg, 25-mg, 40-mg, and 120-mg) will be studied. Subjects will only be assigned to one of the doses for the entire duration of the study period of 28 days. These tablets will be administered orally once daily under fasted conditions for 28 days.
Sponsors
Gilead Sciences, Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2. Must be between 18 and 65 years of age, inclusive on the date of the screening visit 3. Must have Screening plasma HBV DNA greater than or equal to 2x103 IU/mL 4. Eligible subjects must have chronic hepatitis B infection documented to be at least 6 months in duration (e.g. by positive serum HBsAg) 5. Have estimated creatinine clearance (CLCr) > 70 mL/min (using the Cockcroft-Gault method) {2202} based on serum creatinine and actual body weight as measured at the Screening evaluation, ie,: Male: (140 – age in years) x (wt in kg) = CLCr (mL/min) 72 x (serum creatinine in mg/dL) Female: (140 – age in years) x (wt in kg) x 0.85 = CLCr (mL/min) 72 x (serum creatinine in mg/dL) 6. A female subject is eligible to enter the study if she is: Not pregnant or nursing Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure), or are postmenopausal – women > 50 years of age with permanent cessation of previously occurring menses greater than or equal to 12 months as a result of ovarian failure with documentation of hormonal deficiency * Of childbearing potential (i.e., women who have not had a hysterectomy, both ovaries removed or no medically documented ovarian failure). Women greater than or equal to 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to randomization and agree to 1 of the following: * Complete abstinence from intercourse from the date of Screening until 30 days following the last dose of study drugs OR * Consistent and correct use of 1 of the following protocol recommended methods of birth control, in addition to a male partner who correctly uses a condom from the date of Screening until 30 days after the last dose of study drugs - implants of levonorgestrel - injectable progesterone - any intrauterine device (IUD) with a documented failure rate of less than 1% per year - oral contraceptives (either combined or progesterone only), subjects should have been using this method for 3 months prior to initiating study drugs - female barrier method: cervical cap or diaphragm - vaginal ring - transdermal contraceptive patch - tubal sterilization - vasectomy in male subject or male partner 7. All male subjects must agree to consistently and correctly use a condom while their female partner agrees to use 1 of the appropriate medically accepted methods of birth control listed above from the date of Screening until 30 days after their last dose of study drugs 8. Male subjects must agree to refrain from sperm donation for at least 60 days after the last dose 9. Subjects must refrain from blood donation from baseline/Day 1 through completion of the study and continuing for at least 30 days from date of last dose of study drug 10. Subjects must, in the opinion of the Investigator, be in good general health based upon medical history, physical examination (including vital signs), and Screening laboratory evaluations (hematology, chemistry, and urinalysis must fall within the central laboratory’s reference normal ranges unless the results have been determined by the Investigator to have no clinical significance): - ALT (SGPT) greater than or equal to 10 X ULN at Screening - Adequate hematologic function (absolute neutrophil count > or = 1,500/mm3 or > or = 1,000/mm3 if considered a physiologic variant in a subject of African decent; hemoglobin > or = 10.0 g/dL) 11. Must be willing and able to comply with all study requirements
Exclusion criteria
1. Pregnant or lactating subjects 2. Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior Interferon treatment, greater than 6 months prior to screening, are permitted to participate in the study 3. Known co-infection with HIV, HCV or HDV 4. Presence of autoimmune disorders (eg, systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, psoriasis of greater than mild severity) 5. Have a history of liver disease other than Hepatitis B 6. Have a history of Gilbert’s Disease 7. Known or suspected cirrhosis 8. Evidence of hepatocellular carcinoma (eg, fetoprotein > 50 ng/mL or as indicated by recent ultrasound or other standard of care measure) 9. Any sign of decompensated liver disease, including prothrombin time greater than or equal to 1.5 x ULN, platelets < 100,000/mm3 or albumin < 3.5 g/dL at Screening OR current or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy or variceal hemorrhage) 10. Have a history or family history of Long QT Syndrome, Wolfe-Parkinson-White Syndrome, or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual between the ages of 1 and 40 years 11. Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities 12. Have clinically relevant electrolyte abnormalities 13. History of medical or surgical treatment that permanently alters the gastric condition (eg, gastrectomy) 14. Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to the study dosing 15. Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance 16. Subjects having a positive screen for amphetamines, barbiturates, cocaine, or methadone at either the Screening or baseline/day 1 visit are not permitted to participate in the study. Subjects having a positive screen for barbiturates, benzodiazepines, and/or opiates at the Screening evaluation may be re tested at baseline/Day 1. Subjects on stable methadone maintenance may be considered after discussion with the medical monitor 17. Have a history of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy 18. Have consumed grapefruit, grapefruit juice, pomegranate juice or Seville orange juice within 7 days prior to Day 1 19. Known hypersensitivity to the study drugs, the metabolites or formulation excipients 20. Are unable to comply with study requirements 21. Have a history of bleeding diathesis 22. Significant bone disease, (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures 23. Believed by the study Investigator, to be inappropriate for study participation for any reason including any not otherwise listed. For example: renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (eg, diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment
Outcome results
None listed