Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B

Ching Lung Lai, Sang Hoon Ahn, Kwan Sik Lee, Soon Ho Um, Mong Cho, Seung Kew Yoon, Jin Woo Lee, Neung Hwa Park, Young Oh Kweon, Joo Hyun Sohn, Jiyoon Lee, Jeong Ae Kim, Kwang Hyub Han, Man Fung Yuen

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Abstract

Background: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. Design: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. Results: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (<20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p>0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively ( p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. Conclusions: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.

Original languageEnglish
Pages (from-to)996-1004
Number of pages9
JournalGut
Volume63
Issue number6
DOIs
Publication statusPublished - 2014 Jun 1

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Chronic Hepatitis B
Carnitine
Hepatitis B virus
Hepatitis B e Antigens
DNA
Serum
((1-((2-amino-9H-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonic acid dipivoxyl
entecavir
Organophosphonates
Lamivudine
Alanine Transaminase
Biochemistry
Antiviral Agents
Creatinine
Nucleotides
Safety
Mutation

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Lai, Ching Lung ; Ahn, Sang Hoon ; Lee, Kwan Sik ; Um, Soon Ho ; Cho, Mong ; Yoon, Seung Kew ; Lee, Jin Woo ; Park, Neung Hwa ; Kweon, Young Oh ; Sohn, Joo Hyun ; Lee, Jiyoon ; Kim, Jeong Ae ; Han, Kwang Hyub ; Yuen, Man Fung. / Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. In: Gut. 2014 ; Vol. 63, No. 6. pp. 996-1004.
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title = "Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B",
abstract = "Background: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. Design: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. Results: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (<20 IU/mL) were 63.6{\%}, 62.9{\%} and 58.3{\%}, respectively (p>0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively ( p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7{\%}, 76.9{\%}, 89.7{\%}, respectively) and HBeAg seroconversion (11.11{\%}, 15{\%}, 9.52{\%}, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1{\%}) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. Conclusions: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.",
author = "Lai, {Ching Lung} and Ahn, {Sang Hoon} and Lee, {Kwan Sik} and Um, {Soon Ho} and Mong Cho and Yoon, {Seung Kew} and Lee, {Jin Woo} and Park, {Neung Hwa} and Kweon, {Young Oh} and Sohn, {Joo Hyun} and Jiyoon Lee and Kim, {Jeong Ae} and Han, {Kwang Hyub} and Yuen, {Man Fung}",
year = "2014",
month = "6",
day = "1",
doi = "10.1136/gutjnl-2013-305138",
language = "English",
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pages = "996--1004",
journal = "Gut",
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}

Lai, CL, Ahn, SH, Lee, KS, Um, SH, Cho, M, Yoon, SK, Lee, JW, Park, NH, Kweon, YO, Sohn, JH, Lee, J, Kim, JA, Han, KH & Yuen, MF 2014, 'Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B', Gut, vol. 63, no. 6, pp. 996-1004. https://doi.org/10.1136/gutjnl-2013-305138

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. / Lai, Ching Lung; Ahn, Sang Hoon; Lee, Kwan Sik; Um, Soon Ho; Cho, Mong; Yoon, Seung Kew; Lee, Jin Woo; Park, Neung Hwa; Kweon, Young Oh; Sohn, Joo Hyun; Lee, Jiyoon; Kim, Jeong Ae; Han, Kwang Hyub; Yuen, Man Fung.

In: Gut, Vol. 63, No. 6, 01.06.2014, p. 996-1004.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B

AU - Lai, Ching Lung

AU - Ahn, Sang Hoon

AU - Lee, Kwan Sik

AU - Um, Soon Ho

AU - Cho, Mong

AU - Yoon, Seung Kew

AU - Lee, Jin Woo

AU - Park, Neung Hwa

AU - Kweon, Young Oh

AU - Sohn, Joo Hyun

AU - Lee, Jiyoon

AU - Kim, Jeong Ae

AU - Han, Kwang Hyub

AU - Yuen, Man Fung

PY - 2014/6/1

Y1 - 2014/6/1

N2 - Background: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. Design: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. Results: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (<20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p>0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively ( p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. Conclusions: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.

AB - Background: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. Design: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. Results: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (<20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p>0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively ( p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. Conclusions: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.

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