Clinical trial: A phase II, randomized study evaluating the safety, pharmacokinetics and anti-viral activity of clevudine for 12 weeks in patients with chronic hepatitis B

Alimentary Pharmacology and Therapeutics

Volumn 27, Issue 12, 2008, Pages 1282-1292

  Lim, S G ^a   Leung, N ^b   Hann, H W L ^c   Lau, G K K ^d   Trepo, C ^e   Mommeja Marin, H ^f   Moxham, C ^f   Sorbel, J ^f   Snow, A ^f   Blum, M R ^f   Rousseau, F ^f   Marcellin, P ^g  

^a NATIONAL UNIVERSITY HOSPITAL   (Singapore)

^b CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^c THOMAS JEFFERSON UNIVERSITY HOSPITAL   (United States)

^d UNIVERSITY OF HONG KONG   (Hong Kong)

^e HÔTEL DIEU   (France)

^f GILEAD SCIENCES INC   (United States)

^g CENTRE DE RECHERCHE BIOMÉDICALE BICHAT BEAUJON CRB3   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CLEVUDINE;

ABDOMINAL PAIN; ADULT; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; BACKACHE; BRONCHITIS; CHRONIC HEPATITIS; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; COUGHING; CREATINE KINASE BLOOD LEVEL; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FEVER; FLU LIKE SYNDROME; GENOTYPE; HEADACHE; HEPATITIS B; HEPATITIS B VIRUS; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; OPTIMAL DRUG DOSE; PARESTHESIA; PHARMACODYNAMICS; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REBOUND; RECTUM DISEASE; SIDE EFFECT; STATISTICAL ANALYSIS; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS LOAD;

ADOLESCENT; ADULT; ANTIBODIES, VIRAL; ANTIVIRAL AGENTS; ARABINOFURANOSYLURACIL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; GENOTYPE; HEPATITIS B, CHRONIC; HUMANS; MALE; MIDDLE AGED; TREATMENT OUTCOME;

EID: 43849084211     PISSN: 02692813     EISSN: 13652036     Source Type: Journal    
DOI: 10.1111/j.1365-2036.2008.03686.x     Document Type: Article

References (21)

1. Lee WM. Hepatitis B virus infection. N Engl J Med 1997 337 : 1733 45.
2. Wong DK, Cheung AM, O'Rourke K, Naylor CD, Detsky AS, Heathcote J. Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 1993 119 : 312 23.
3. Leung NW, Lai CL, Chang TT, et al. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology 2001 33 : 1527 32.
4. Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003 348 : 808 16.
5. Hadziyannis SJ, Papatheodoridis GV. Treatment of HBeAg negative chronic hepatitis B with new drugs (adefovir and others). J Hepatol 2003 39 (Suppl. 1 S172 6.
6. Lai CL, Shouval D, Lok AS, et al. Entecavir vs. lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006 354 : 1011 20.
7. Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006 354 : 1001 10.
8. Lai CL, Gane E, Liaw YF, et al. Telbivudine vs. lamivudine in patients with chronic hepatitis B. N Engl J Med 2007 357 : 2576 88.
9. Chu CK, Ma T, Shanmuganathan K, et al. Use of 2'-fluoro-5-methyl-beta-L- arabinofuranosyluracil as a novel antiviral agent for hepatitis B virus and Epstein-Barr virus. Antimicrob Agents Chemother 1995 39 : 979 81.
10. Chin R, Shaw T, Torresi J, et al. In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-d-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-l-arabinofuranosyluracil. Antimicrob Agents Chemother 2001 45 : 2495 501.
11. Ma T, Pai SB, Zhu YL, et al. Structure-activity relationships of 1-(2-Deoxy-2-fluoro-beta-l-arabinofuranosyl)pyrimidine nucleosides as anti-hepatitis B virus agents. J Med Chem 1996 39 : 2835 43.
12. Liu SH, Grove KL, Cheng YC. Unique metabolism of a novel antiviral L-nucleoside analog, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil: a substrate for both thymidine kinase and deoxycytidine kinase. Antimicrob Agents Chemother 1998 42 : 833 9.
13. Peek SF, Cote PJ, Jacob JR, et al. Antiviral activity of clevudine [l-FMAU, (1-(2-fluoro-5-methyl-beta, l-arabinofuranosyl) uracil)] against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks (Marmota monax). Hepatology 2001 33 : 254 66.
14. Chu CK, Boudinot FD, Peek SF, et al. Preclinical investigation of L-FMAU as an anti-hepatitis B virus agent. Antivir Ther 1998 3 (Suppl. 3 113 21.
15. Marcellin P, Mommeja-Marin H, Sacks SL, et al. A phase II dose-escalating trial of clevudine in patients with chronic hepatitis B. Hepatology 2004 40 : 140 8.
16. Yoo BC, Kim JH, Chung YH, et al. Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B. Hepatology 2007 45 : 1172 8.
17. Yoo BC, Kim JH, Kim TH, et al. Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression. Hepatology 2007 46 : 1041 8.
18. Lee HS, Chung YH, Lee K, et al. A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B. Hepatology 2006 43 : 982 8.
19. Yamamoto T, Litwin S, Zhou T, et al. Mutations of the woodchuck hepatitis virus polymerase gene that confer resistance to lamivudine and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil. J Virol 2002 76 : 1213 23.
20. Fu L, Cheng YC. Characterization of novel human hepatoma cell lines with stable hepatitis B virus secretion for evaluating new compounds against lamivudine- and penciclovir-resistant virus. Antimicrob Agents Chemother 2000 44 : 3402 7.
21. Yeh CT, Chien RN, Chu CM, Liaw YF. Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy. Hepatology 2000 31 : 1318 26.