Randomized, double-blind study of emtricitabine (FTC) plus clevudine versus FTC alone in treatment of chronic hepatitis B.
Emtricitabine (FTC) is approved for the treatment of human immunodeficiency virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV). This report summarizes the results of a double-blind, multicenter study of patients with chronic hepatitis B who had completed a phase 3 study of FTC and were randomized 1:1 to 200 mg FTC once daily (QD) plus 10 mg CLV QD or 200 mg FTC QD plus placebo for 24 weeks with 24 weeks of follow-up. One hundred sixty-three patients were treated (82 with FTC plus CLV [FTC+CLV] and 81 with FTC); 72% were men, 53% were Asian, 47% were Caucasian, and 52% were hepatitis B e antigen positive, and the median baseline HBV DNA level was 6 log(10) copies/ml. After 24 weeks of treatment, 74% (FTC+CLV) versus 65% (FTC alone) had serum HBV DNA levels of <4,700 copies/ml (P = 0.114) (Digene HBV Hybrid Capture II assay). Twenty-four weeks posttreatment, the mean change in serum HBV DNA levels from baseline was -1.25 log(10) copies/ml (FTC+CLV), 40% had undetectable viremia (versus 23% for FTC alone), and 63% had normal alanine aminotransferase levels (versus 42% for FTC alone) (P < or = 0.025 for all endpoints). The safety profile was similar between arms during treatment, with less posttreatment exacerbation of hepatitis B in the combination arm. In summary, after 24 weeks of treatment, no significant difference between arms was observed, but there was a significantly greater virologic and biochemical response 24 weeks posttreatment in the FTC+CLV arm.
Lim
Seng Gee
SG
Gilead Sciences Inc., 4 University Place, 4611 University Drive, Durham, NC 27707, USA.
Krastev
Zahary
Z
Ng
Tay Meng
TM
Mechkov
Grigor
G
Kotzev
Iskren Andreev
IA
Chan
Sing
S
Mondou
Elsa
E
Snow
Andrea
A
Sorbel
Jeff
J
Rousseau
Franck
F
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000681:Amylases / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001639:Bicarbonates / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003402:Creatine Kinase / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004573:Electrolytes / Q000097:blood; D000068679:Emtricitabine; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012709:Serum Albumin / Q000032:analysis
D000998:Antiviral Agents; D001639:Bicarbonates; D001786:Blood Glucose; D004279:DNA, Viral; D004573:Electrolytes; D006513:Hepatitis B e Antigens; D012709:Serum Albumin; D003841:Deoxycytidine; D001086:Arabinofuranosyluracil; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; D000469:Alkaline Phosphatase; D000681:Amylases; D000068679:Emtricitabine; C034935:clevudine; D001663:Bilirubin