Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial
| Autor: | Liang Chen, Yanzhong Peng, Chunmei Liu, Guangming Li, Hesong Cui, Zong Zhang, Weidong Liu, Z.S. Jin, Xinwen Song, Qing Mao, Qianguo Mao, Yanhang Gao, Jia Shang, Junqi Niu, Xueyuan Jin, Peng Wang, Dengke Zhang, Fei Kong, Jidong Jia, Xiaolu Wu, Daidi Wang, Xiuhong Wen, Caiyan Zhao, Huanyu Gong, Wen Chen, Yanhua Ding, Lvfeng Yao, Xuebing Yan, Qingjing Zhu, Yongfeng Yang, Jinyu Xia, Mao Mu, Weili Jin, Tao Han |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Hepatitis B virus medicine.medical_specialty Cirrhosis Phases of clinical research medicine.disease_cause Antiviral Agents Gastroenterology Hepatitis B Chronic Organophosphorus Compounds Internal medicine medicine Adefovir Humans Prodrugs Hepatitis B e Antigens Tenofovir Adverse effect Pradefovir business.industry Adenine Viral Load Hepatitis B medicine.disease Treatment Outcome Infectious Diseases HBeAg DNA Viral business medicine.drug |
| Zdroj: | Clinical Infectious Diseases. 74:1925-1932 |
| ISSN: | 1537-6591 1058-4838 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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