A Double-blind Placebo-Controlled Study of Emtricitabine in Chronic Hepatitis B

January 11, 2006

ARCHIVES OF INTERNAL MEDICINE

Vol. 166 No. 1, January 9, 2006

A Double-blind Placebo-Controlled Study of Emtricitabine in Chronic

Hepatitis B

Seng Gee Lim, MD; Tay Meng Ng, MD; Kung, MD; Zahary Krastev, MD, PhD;

Miroslava Volfova, MD, PhD; Petr Husa, MD, PhD; S. Lee, MD; Sing

Chan, MD; L. Shiffman, MD; Kay Washington, MD, PhD; Amy

Rigney, MEd; Jane , PhD; Elsa Mondou, MD; Snow, BS; Jeff

Sorbel, MS; Guan, MD; Franck Rousseau, MD; for the Emtricitabine

FTCB-301 Study Group

Arch Intern Med. 2006;166:49-56.

Background Emtricitabine is a nucleoside analogue approved for treatment of

human immunodeficiency virus 1 with clinical activity against hepatitis B

virus (HBV).

Methods To compare the safety and efficacy of emtricitabine with placebo in

patients with HBV, we conducted a randomized (2:1), double-blind study at 34

sites in North America, Asia, and Europe that enrolled adults between

November 2000 and July 2002 who had chronic HBV infection but had never been

exposed to nucleoside or nucleotide treatment. Each patient received either

200 mg of emtricitabine (n = 167) or placebo (n = 81) once daily for 48

weeks and underwent a pretreatment and end-of-treatment liver biopsy.

Histologic improvement was defined as a 2-point reduction in Knodell

necroinflammatory score with no worsening in fibrosis.

Results At the end of treatment, 103 (62%) of 167 patients receiving active

treatment had improved liver histologic findings vs 20 (25%) of 81 receiving

placebo (P<.001), with significance demonstrated in subgroups positive

(P<.001) and negative (P = .002) for hepatitis Be (HBe) antigen. Serum HBV

DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in

the emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001);

alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81),

respectively (P<.001). At week 48, 20 (13%) of 159 patients in the

emtricitabine group with HBV DNA measured at the end of treatment had

detectable virus with resistance mutations (95% confidence interval,

8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss

were not different between arms. The safety profile of emtricitabine during

treatment was similar to that of placebo. Posttreatment exacerbation of HBV

infection developed in 23% of emtricitabine-treated patients.

Conclusion In patients with chronic HBV, both positive and negative for HBe

antigen, 48 weeks of emtricitabine treatment resulted in significant

histologic, virologic, and biochemical improvement.

Author Affiliations: National University Hospital (Dr Lim), Changi General

Hospital (Dr Ng), and Mount Medical Center (Dr Guan), Singapore;

United Christian Hospital, Kowloon, Hong Kong Special Administrative Region,

China (Dr Kung); University Hospital " St Ivan Rilsky, " Sofia, Bulgaria (Dr

Krastev); University Hospital Hradec Kralove (Dr Volfova) and University

Hospital Brno (Dr Husa), Brno, Czech Republic; University of Calgary,

Calgary, Alberta (Dr Lee); New York Hospital at Queens, Flushing, NY (Dr

Chan); Virginia Commonwealth University Medical Center, Richmond, Va (Dr

Shiffman); Vanderbilt University Medical Center, Nashville, Tenn (Dr

Washington); and Gilead Sciences Inc, Durham, NC (Drs , Mondou, and

Rousseau, Mss Rigney and Snow, and Mr Sorbel).

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January 11, 2006