PMID- 34487151
OWN - NLM
STAT- MEDLINE
DCOM- 20220614
LR  - 20220716
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 74
IP  - 11
DP  - 2022 Jun 10
TI  - Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a 
      Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial.
PG  - 1925-1932
LID - 10.1093/cid/ciab763 [doi]
AB  - BACKGROUND: Pradefovir is a liver-targeted prodrug of adefovir, a 
      nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus 
      (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral 
      pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 
      mg) and aimed to identify the most appropriate dose of pradefovir for the 
      forthcoming phase 3 study. METHODS: Treatment-naive and experienced (not on 
      treatment >6 months) patients with chronic hepatitis B were eligible. RESULTS: A 
      total of 240 participants were randomized and treated in the study (48 per 
      group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% 
      had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at 
      week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 
      30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. 
      However, HBeAg loss was attained by more participants who received 45-, 60-, or 
      75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF 
      group exhibited a more significant increase in serum creatinine than the 
      pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among 
      all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related 
      severe AEs were reported. Overall, AEs and laboratory abnormalities were 
      comparable to those in the TDF group. CONCLUSIONS: Pradefovir and TDF exhibited 
      comparable reductions in HBV DNA levels. All treatments were safe and well 
      tolerated. CLINICAL TRIALS REGISTRATION: NCT00230503 and China Drug Trials 
      CTR2018042.
CI  - (c) The Author(s) 2021. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Gao, Yanhang
AU  - Gao Y
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun, 
      Jilin, China.
FAU - Kong, Fei
AU  - Kong F
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun, 
      Jilin, China.
FAU - Song, Xinwen
AU  - Song X
AD  - Department of Infectious Diseases, The First Affiliated Hospital of Xinxiang 
      Medical University, Xinxiang, Henan, China.
FAU - Shang, Jia
AU  - Shang J
AD  - Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, 
      Henan, China.
FAU - Yao, Lvfeng
AU  - Yao L
AD  - Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical 
      University, Fuzhou, Fujian, China.
FAU - Xia, Jinyu
AU  - Xia J
AD  - Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen 
      University, Zhuhai, Guangdong, China.
FAU - Peng, Yanzhong
AU  - Peng Y
AD  - Department of Infectious Diseases, Peking University Shenzhen Hospital, Shenzhen, 
      China.
FAU - Liu, Weidong
AU  - Liu W
AD  - Department of Hepatology, The Second Affiliated Hospital of Shantou University 
      Medical College, Shantou, Guangdong, China.
FAU - Gong, Huanyu
AU  - Gong H
AD  - Department of Infectious Diseases, The Third Xiangya Hospital of Central South 
      University, Changsha, Hunan, China.
FAU - Mu, Mao
AU  - Mu M
AD  - Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical 
      University, Guiyang, Guizhou, China.
FAU - Cui, Hesong
AU  - Cui H
AD  - Department of Infectious Diseases, Yanbian University Affiliated Hospital, Yanji, 
      Jilin, China.
FAU - Han, Tao
AU  - Han T
AD  - Department of Hepatology, Tianjin Third Central Hospital, Tianjin, China.
FAU - Chen, Wen
AU  - Chen W
AD  - Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan, China.
FAU - Wu, Xiaolu
AU  - Wu X
AD  - Department of Infectious Diseases, The First Affiliated Hospital of Xiamen 
      University, Xiamen, Fujian, China.
FAU - Yang, Yongfeng
AU  - Yang Y
AD  - Department of Hepatology, The Second Hospital of Nanjing, Nanjing, Jiangsu, 
      China.
FAU - Yan, Xuebing
AU  - Yan X
AD  - Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical 
      University, Xuzhou, China.
FAU - Jin, Zhenjing
AU  - Jin Z
AD  - Department of Hepatology, The Second Hospital of Jilin University, Changchun, 
      China.
FAU - Wang, Peng
AU  - Wang P
AD  - Department of Infectious Diseases, Shunde Hospital of Southern Medical 
      University, Foshan, Guangdong, China.
FAU - Zhu, Qingjing
AU  - Zhu Q
AD  - Department of Hepatology, Wuhan Hospital for Infectious Diseases, Wuhan, Hubei, 
      China.
FAU - Chen, Liang
AU  - Chen L
AD  - Department of Infectious Diseases, Shanghai Public Health Clinical Center, 
      Shanghai, China.
FAU - Zhao, Caiyan
AU  - Zhao C
AD  - Department of Infectious Diseases, The Third Hospital of Hebei Medical 
      University, Shijiazhuang, Hebei, China.
FAU - Zhang, Dengke
AU  - Zhang D
AD  - Xi'an Xintong Pharmaceutical Research, Xi'an, Shanxi, China.
FAU - Jin, Weili
AU  - Jin W
AD  - Xi'an Xintong Pharmaceutical Research, Xi'an, Shanxi, China.
FAU - Wang, Daidi
AU  - Wang D
AD  - Xi'an Xintong Pharmaceutical Research, Xi'an, Shanxi, China.
FAU - Wen, Xiuhong
AU  - Wen X
AD  - Xi'an Xintong Pharmaceutical Research, Xi'an, Shanxi, China.
FAU - Liu, Chunmei
AU  - Liu C
AD  - Xi'an Xintong Pharmaceutical Research, Xi'an, Shanxi, China.
FAU - Jia, Jidong
AU  - Jia J
AD  - Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Mao, Qing
AU  - Mao Q
AD  - Institute of Infectious Diseases, First Affiliated Hospital of People's 
      Liberation Army Medical University, Chongqing, China.
FAU - Ding, Yanhua
AU  - Ding Y
AD  - Department of Phase I Clinical Trial, The First Hospital of Jilin University, 
      Changchun, Jilin, China.
FAU - Jin, Xueyuan
AU  - Jin X
AD  - Department of Quality Management, The Fifth Medical Center of Chinese PLA General 
      Hospital, Beijing, China.
FAU - Zhang, Zong
AU  - Zhang Z
AD  - Department of Hepatology, Jinan Hospital for Infectious Disease, Jinan, Shandong, 
      China.
FAU - Mao, Qianguo
AU  - Mao Q
AD  - Department of Hepatology, Chinese Medicine Xiamen Hospital, Xiamen, Fujian, 
      China.
FAU - Li, Guangming
AU  - Li G
AD  - Cirrhosis Department, Zhengzhou Sixth Municipal People's Hospital, Zhengzhou, 
      Henan, China.
FAU - Niu, Junqi
AU  - Niu J
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun, 
      Jilin, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT00230503
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Hepatitis B e Antigens)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Prodrugs)
RN  - 99YXE507IL (Tenofovir)
RN  - GZE85Q9Q61 (pradefovir)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/analogs & derivatives
MH  - Antiviral Agents/adverse effects
MH  - DNA, Viral
MH  - Hepatitis B e Antigens
MH  - Hepatitis B virus/genetics
MH  - *Hepatitis B, Chronic
MH  - Humans
MH  - Organophosphorus Compounds
MH  - *Prodrugs/adverse effects
MH  - Tenofovir/adverse effects
MH  - Treatment Outcome
MH  - Viral Load
PMC - PMC9187326
OTO - NOTNLM
OT  - efficacy
OT  - hepatitis B
OT  - pradefovir
OT  - safety
OT  - tenofovir disoproxil fumarate
EDAT- 2021/09/07 06:00
MHDA- 2022/06/15 06:00
PMCR- 2021/09/06
CRDT- 2021/09/06 12:18
PHST- 2021/05/17 00:00 [received]
PHST- 2021/09/07 06:00 [pubmed]
PHST- 2022/06/15 06:00 [medline]
PHST- 2021/09/06 12:18 [entrez]
PHST- 2021/09/06 00:00 [pmc-release]
AID - 6364928 [pii]
AID - ciab763 [pii]
AID - 10.1093/cid/ciab763 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2022 Jun 10;74(11):1925-1932. doi: 10.1093/cid/ciab763.