Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection

Zhang, Hong; Wu, Min; Zhu, Xiaodong; Li, Cuiyun; Li, Xiaojiao; Jin, Weili; Zhang, Dengke; Chen, Hong; Liu, Chengjiao; Ding, Yanhua; Niu, Junqi; Liu, Jingrui

doi:10.1016/j.antiviral.2019.104693

Cited by 13 publications

(19 citation statements)

References 27 publications

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“…A 48-weeks Phase II trial involving chronically infected HBV patients further confirmed that pradefovir mesylate (dosed at 5-30 mg/day) was well-tolerated and significantly more active than 19 (dosed at 10 mg/day), without producing significant changes in kidney function markers (Lee et al, 2006). Although further clinical evaluation of 21 was discontinued in USA and Europe due to the potential carcinogenic effect observed in animal studies, a Phase III trial for the treatment of patients with chronic HBV infections is currently ongoing in China to determine (ClinicalTrials.gov Identifier: NCT04543565; Recruitment Status: Recruiting) (Zhang et al, 2020).…”

Section: Anti-hepadnaviral and Anti-retroviral Nucleoside Phosphonatesmentioning

confidence: 99%

Overview of Biologically Active Nucleoside Phosphonates

Groaz

Jonghe

2021

Front. Chem.

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The use of the phosphonate motif featuring a carbon-phosphorous bond as bioisosteric replacement of the labile P–O bond is widely recognized as an attractive structural concept in different areas of medicinal chemistry, since it addresses the very fundamental principles of enzymatic stability and minimized metabolic activation. This review discusses the most influential successes in drug design with special emphasis on nucleoside phosphonates and their prodrugs as antiviral and cancer treatment agents. A description of structurally related analogs able to interfere with the transmission of other infectious diseases caused by pathogens like bacteria and parasites will then follow. Finally, molecules acting as agonists/antagonists of P2X and P2Y receptors along with nucleotidase inhibitors will also be covered. This review aims to guide readers through the fundamentals of nucleoside phosphonate therapeutics in order to inspire the future design of molecules to target infections that are refractory to currently available therapeutic options.

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Section: Anti-hepadnaviral and Anti-retroviral Nucleoside Phosphonatesmentioning

confidence: 99%

Overview of Biologically Active Nucleoside Phosphonates

Groaz

Jonghe

2021

Front. Chem.

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“…Therefore, the dosage for HS-10234 in a phase II trial could be 10-25 mg QD. 17,22,23 In conclusion, this phase Ib trial found that a 28-day treatment regimen with HS-10234, a new TFV prodrug, was safe and well-tolerated in this cohort. The anti-viral efficacy of HS-10234, regardless of dose, resembled TDF.…”

Section: Discussionmentioning

confidence: 62%

“…The AI of TFV was low, which helps design QD dosing of HS-10234. 9,10,17 The systemic TFV level in the 25 mg HS-10234 group was reduced by 88.4%, which resembled 92% reduction after 25 mg TAF (another phosphonate prodrug of tenofovir) compared with 300 mg TDF in CHB patients. 9 After 10 days of treatment with 25 mg TAF, TFV exposures (AUC tau ) were reduced by 86% and TFV-DP increased sevenfold, compared to the exposure level detected upon administration of 300 mg TDF in HIV-infected patients.…”

Section: Discussionmentioning

confidence: 81%

“…These results confirmed the expected PK and drug exposures of HS-10234 and the comparable levels of the metabolites TFV and TFV-DP between HS-10234 and TAF. 10,17,18 CHB patients with cirrhosis of Child-Pugh A were allowed to enroll per inclusion and exclusion criteria, including two patients in 10 mg group with early stage cirrhosis detected by ultrasound with the liver stiffness of 10.1 and 10.7 kPa, respectively. Six patients with liver stiffness >17.5 kPa (though no cirrhosis indicated by Ultrasound) were also enrolled and all of them were at Child-Pugh A.…”

Section: Discussionmentioning

confidence: 99%

“…The PK values of TFV were also dose‐responsive and showed efficient transformation from HS‐10234 (median T max , 0.75‐1.0 hours) and relatively slow plasma elimination (mean t 1/2 , 25.95‐43.22 hours). The AI of TFV was low, which helps design QD dosing of HS‐10234 9,10,17 …”

Section: Discussionmentioning

confidence: 99%

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Randomised clinical trial: safety, efficacy and pharmacokinetics of HS‐10234 versus tenofovir for the treatment of chronic hepatitis B infection

Zhang

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundHS‐10234 is a novel prodrug of tenofovir developed to increase anti‐viral potency and to reduce systemic toxicities.AimsTo evaluate the tolerability, pharmacokinetics and anti‐viral efficacy of HS‐10234 in patients with chronic hepatitis B (CHB) infectionMethodsTreatment‐naïve subjects with non‐cirrhotic CHB were divided into three groups (n = 12/group) and randomised within each group to receive 10, 25 or 40 mg of HS‐10234, or 300 mg of tenofovir disoproxil fumarate (TDF) once a day for 28 days.ResultsAmong 36 enrolled subjects, 33.3% were hepatitis B e antigen‐negative with a mean hepatitis B virus (HBV) DNA level of 6.32‐7.42 log10 IU/mL. Nephrotoxicity and serious adverse events were not observed; all adverse events were mild or moderate and non‐specific. The mean reductions in serum HBV DNA after 28 days were −2.70, −2.89, −2.72 and −3.04 log10 IU/mL for treatment with 10, 25 or 40 mg HS‐10234, and 300 mg TDF, respectively. HS‐10234 and its metabolite TFV showed linear, dose‐proportional pharmacokinetics. The concentrations of active TFV‐DP in peripheral blood mononuclear cells were higher (approximately 2‐ to 11‐fold increase) and TFV in plasma were lower (approximately 4.5‐ to 25‐fold reduction) in subjects taking HS‐10234 than those in the TDF group.ConclusionsHS‐10234 was well tolerated during a 4‐week course. TDF and HS‐10234 had comparable potency in inhibiting HBV replication. A daily dose of 10‐25 mg of HS‐10234 is recommended for CHB treatment. (Chinese Drug Trial Identifier: CTR20161077).

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Establishing an evaluation index system of nursing quality for clinical drug trials: A Delphi study

Chen,

Zhou,

Mai

et al. 2023

Nursing Open

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AimsTo construct a quality evaluation index system for clinical drug trials nursing management and obtain the weight of all indicators.DesignA mixed‐method research design with a quantitative component was used, primarily qualitative.MethodsThrough a literature review and semi‐structured interview, an expert consultation questionnaire on the quality of nursing evaluation indicators for clinical drug trials was developed in April 2021. Eighteen experts in clinical drug trial nursing, medical, and pharmacy conducted 2 rounds of consultation according to the Delphi method to determine the indicators for evaluating the quality of clinical drug trial nursing. The weights of each indicator were determined using analytic hierarchical analysis.ResultsThe established quality evaluation system of clinical drug trial nursing mainly includes 3 first‐level indicators, 12 second‐level indicators, and 59 third‐level indicators. The positive coefficients of the two rounds of expert consultation were 90%–100%, and the authority coefficients were 0.831 and 0.885, respectively; the coordination coefficients were 0.189 and 0.214, respectively. The consulting results and weight settings are reliable. The evaluation index system we constructed is in line with the characteristics of the clinical drug trial nursing profession, with clear index levels and strong clinical operability, which can provide a reference for the assessment, monitoring and improvement of nursing quality in clinical drug trials. It will also clarify how nurses contribute to subjects' safety.

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Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection

Cited by 13 publications

References 27 publications

Overview of Biologically Active Nucleoside Phosphonates

Overview of Biologically Active Nucleoside Phosphonates

Randomised clinical trial: safety, efficacy and pharmacokinetics of HS‐10234 versus tenofovir for the treatment of chronic hepatitis B infection

Establishing an evaluation index system of nursing quality for clinical drug trials: A Delphi study

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