Dataset Information

Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study.

ABSTRACT:

Background and aims

Canocapavir (ZM-H1505R) is a small-molecule hepatitis B virus capsid assembly modulator with a novel pyrazole structure. This is the first-in-human study to investigate its safety, tolerability, and pharmacokinetics (PK) following oral administration in healthy subjects.

Methods

This was a randomized, double-blind, placebo-controlled study including single ascending dose (SAD) study with an additional crossover food-effect arm, and multiple ascending dose study. In SAD, 40 subjects, 8 in each cohort, were randomized in a 3:1 ratio to receive a single dose of 25, 75, 150, 300, and 450 mg of Canocapavir or placebo in fasted state. For food-effect study, subjects in the 150 mg cohort of SAD received a second dose (150 mg) of Canocapavir in the fed state after a 7-day washout period. In multiple ascending dose, 24 subjects, 8 in each cohort, were randomized in a 3:1 ratio to receive 75, 150, and 300 mg of Canocapavir or placebo once daily for 14 days. The safety and tolerability were assessed using vital signs, physical evaluation, electrocardiogram, laboratory investigations, and adverse events (AEs). Plasma PK parameters measured included area under the curves, C_max, C_min, T_max, and T_1/2.

Results

Oral administration of single doses (25-450 mg) and multiple doses (75-300 mg) of Canocapavir was well tolerated. The most common AE seen was increased alanine aminotransferase. No dose dependency was observed in incidence and intensity of AEs. Mean plasma area under the curve and C_max of Canocapavir increased dose-proportionally. A significant margin was observed between plasma exposure of Canocapavir and its in vitro anti-hepatitis B virus activity. Food had an effect on its absorption.

Conclusion

The safety and PK profile of Canocapavir support its further evaluation in chronic hepatitis B patients. The study was registered on ClinicalTrial.gov with the number NCT04220801.

SUBMITTER: Jiang X

PROVIDER: S-EPMC11307714 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study.

Jiang Xiuhong X Hua Bo B Liu Gang G Xia Tian T Deng Aiyun A Lu Hui H Guo Ruoling R Wang Zhe Z Liang Bo B Chen Huanming H Jin Qiu Q Zhang Zhijun Z

Gastro hep advances 20230107 4

<h4>Background and aims</h4>Canocapavir (ZM-H1505R) is a small-molecule hepatitis B virus capsid assembly modulator with a novel pyrazole structure. This is the first-in-human study to investigate its safety, tolerability, and pharmacokinetics (PK) following oral administration in healthy subjects.<h4>Methods</h4>This was a randomized, double-blind, placebo-controlled study including single ascending dose (SAD) study with an additional crossover food-effect arm, and multiple ascending dose study ...[more]

PMID: 39132049

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Dataset Information

Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study.

Background and aims

Methods

Results

Conclusion

Publications

Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study.

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