Trial reportAntimicrobial agents and chemotherapy2019
A First-in-Human Trial of GLS4, a Novel Inhibitor of Hepatitis B Virus Capsid Assembly, following Single- and Multiple-Ascending-Oral-Dose Studies with or without Ritonavir in Healthy Adult Volunteers.
Trial report in Antimicrobial agents and chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Trial
- Safety, pharmacokinetics, and antiviral activity of the capsid inhibitor AB-506 from Phase 1 studies in healthy subjects and those with hepatitis B.Hepatology communications · 2022Trial
- Safety, antiviral activity and pharmacokinetics of JNJ-64530440, a novel capsid assembly modulator, as 4 week monotherapy in treatment-naive patients with chronic hepatitis B virus infection.The Journal of antimicrobial chemotherapy · 2022Trial
- Advances in pharmacological interventions for hepatic fibrosis: from pathogenic mechanisms to novel therapeutic targets.Annals of medicine · 2026Review
- Chromatin remodeler BAF maintains HBV cccDNA transcriptional competence and represents a therapeutic target.Nucleic acids research · 2026Article
- Combination therapies for chronic hepatitis B in the era of emerging novel drugs.Hepatology international · 2026Review
- Emerging antiviral drugs and immunotherapy for chronic hepatitis B and associated liver disease.Frontiers in immunology · 2026Review
- Design, Synthesis, and Biological Evaluation of Highly Potent Boronic Acid (Boronate Ester)-Bearing Heteroaryldihydropyrimidine Derivatives as HBV Capsid Assembly Modulators.Journal of medicinal chemistry · 2025Article
- Chronic Hepatitis B: Current Management and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- [Research progress on new drugs for the treatment of chronic hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.CPT: pharmacometrics & systems pharmacology · 2024Article
- A revolutionary oral HBV treatment candidate as innovative therapeutic approach warranting clinical trials.Journal of gastroenterology · 2024Article
- Discovery of carboxyl-containing heteroaryldihydropyrimidine derivatives as novel HBV capsid assembly modulators with significantly improved metabolic stability.RSC medicinal chemistry · 2023Article
- Chronic Hepatitis B Infection: New Approaches towards Cure.Biomolecules · 2023Review
- The progress of molecules and strategies for the treatment of HBV infection.Frontiers in cellular and infection microbiology · 2023Review
- Novel therapeutic strategies for chronic hepatitis B.Virulence · 2022Review
- Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy.Molecules (Basel, Switzerland) · 2021Review
- Design, synthesis and evaluation of heteroaryldihydropyrimidine analogues bearing spiro ring as hepatitis B virus capsid protein inhibitors.European journal of medicinal chemistry · 2021Article
- Amino acid residues at core protein dimer-dimer interface modulate multiple steps of hepatitis B virus replication and HBeAg biogenesis.PLoS pathogens · 2021Article
- Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GLS4 is a novel inhibitor of the hepatitis B virus (HBV) capsid assembly with inhibitory activities against nucleot(s)ide-resistant HBV strains. This study investigated the pharmacokinetics, safety, and tolerability of GLS4 and the effects of food and ritonavir in healthy adults. GLS4 was administered in a single-ascending-dose study over 1 to 240 mg and multiple-ascending-dose study that ranged from 30 mg once daily to 180 mg three times daily. The drug interaction study included sequential design (day 1 for 120 mg GLS4 alone, day 5 for 100 mg ritonavir alone, followed by 9 days of both drugs) and a placebo control (9 days of both 240 mg GLS4 and 100 mg ritonavir). The results showed that the steady-state trough concentration of multiple dosing of GLS4 alone was significantly lower than the 90% effective concentration of 55.7 ng/ml, even with increasing dosing frequency and dosage. An initial dose of 100 mg ritonavir significantly boosted plasma concentration at 24 h of 120 mg GLS4 from 2.40 to 49.8 ng/ml (geometric mean ratio, 20.7; 90% confidence interval, 17.0 to 25.3), while a milder effect was observed on the area under the curve from 0 to 24 h, with a 7.42-fold increase, and on the maximum concentration, with a 4.82-fold increase. The pharmacokinetics change in GLS4 persisted after 9 days of chronic dosing, with a trough concentration of 182 ng/ml. Both single and multiple doses of GLS4 up to 240 mg with or without ritonavir were well tolerated. These results support the investigation of a novel HBV treatment regimen containing GLS4 with 100 mg ritonavir added solely to enhance GLS4 concentrations in plasma. (This study was registered at the China Platform for Registry and Publicity of Drug Clinical Trials [http://www.chinadrugtrials.org.cn] under numbers CTR20132137 and CTR20150230.).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.