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Safety, Tolerability and Pharmacokinetics of Single Ascending and Multiple Oral Doses of Tegoprazan in Healthy Chinese Subjects

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Abstract

Background and Objectives

Tegoprazan is one of the potassium-competitive acid blockers (P-CABs). It exhibits its anti-secretory effects by competitively and reversibly blocking the availability of K+ of the H+, K+-ATPase. This study was designed to investigate the safety and pharmacokinetics of tegoprazan in healthy Chinese subjects.

Methods

Thirty-eight healthy Chinese subjects were recruited in this randomized, single-center, double-blind, placebo-controlled study, with a single ascending dose of 50, 100, 200 mg and a multiple dose of 100 mg for 10 days. The plasma concentration of tegoprazan was determined by a validated liquid chromatography tandem mass spectrometry (LC–MS/MS) method. Pharmacokinetics were evaluated via non-compartmental and compartmental model analysis. Safety was assessed by physical examinations, vital signs, clinical laboratory tests, and electrocardiograms.

Results

No serious adverse event was observed in this study. After single-dose administration (50, 100 and 200 mg), tegoprazan was rapidly absorbed with a median maximum measure plasma concentration (Tmax) at 0.5 h and declined with a terminal (elimination) half-life (t1/2) of 3.87–4.57 h. The maximum measured plasma concentration (Cmax) for tegoprazan was 813.80, 1494.60 and 2829.00 ng/mL. Meanwhile, the corresponding area under the concentration–time curve (AUC) from time zero to infinity (AUC0−inf) was 2761.00, 5980.05 and 11,044.72 ng∙h/mL in 50, 100, 200 mg group, respectively. Dose-dependent increase was observed in the value of Cmax and AUC after administration of tegoprazan 50 to 200 mg. The two-compartment model well described the pharmacokinetic profile of tegoprazan. In the steady state, no accumulation was found after repeated administration at the 100-mg dose level. No experimental differences were found based on gender.

Conclusions

Tegoprazan was well tolerated in the dose range of 50–200 mg in single- and 100 mg in multiple-dose studies. Tegoprazan shows dose linearity with oral administration after a single dose of 50 to 200 mg and less drug accumulation after 10 days of continuous administration in 100 mg.

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Acknowledgements

The authors thank all the volunteers who took part in the trial, as well as the staff that assisted with the trial at study site. The authors would also like to thank HK inno.N and Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. for providing the study drug and reference standards.

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Author notes

  1. Jinjie He and Guoying Cao contributed to the work equally.

Authors and Affiliations

  1. Phase I Clinical Research Center, Huashan Hospital, Fudan University, No.12 in Wurumuqi Road, Jingan Area, Shanghai, China

    Jinjie He, Guoying Cao, Jicheng Yu, Jingjing Wang, Jufang Wu, Jing Zhang & Xiaojie Wu

  2. School of Pharmacy, Fudan University, Shanghai, China

    Nengneng Cheng

  3. Shandong Luoxin Pharmaceutical Group Stock Co., Ltd., Linyi, China

    Basheng Zhang, Jiayan Lu & Shangzhi Chen

Authors
  1. Jinjie He
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  2. Guoying Cao
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  3. Jicheng Yu
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  4. Jingjing Wang
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  5. Nengneng Cheng
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  6. Jufang Wu
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  7. Jing Zhang
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  8. Xiaojie Wu
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  9. Basheng Zhang
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  10. Jiayan Lu
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  11. Shangzhi Chen
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Corresponding author

Correspondence to Jing Zhang.

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Funding

This study was funded by Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. China.

Conflict of interest

B. Zhang, J. Lu, and S. Chen are employees of Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. China. J. He, G. Cao, J. Yu, X. Wu, J. Wang, J. Wu and J. Zhang are employed by the Huashan Hospital, Fudan University, Shanghai, China, which received funding from Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. China to carry out this study. N. Cheng declares he has no conflict of interest.

Ethical approval

The study protocol and informed consent documents were approved by the Ethics Committee of Huashan Hospital, meanwhile the study was licensed in National Medical Products Administration (NMPA) in China with the registration number of 2017L04362, and the Identifier in ClinicalTrials.gov was NCT03458650. Study conduct was in accordance with the principles of International Conference on Harmonization, Declaration of Helsinki, NMPA, and Good Clinical Practice.

Consent to participation

Written informed consent was obtained from all individual participants included in the studies before commencing any study-related procedures.

Consent for publication

Not applicable.

Data availability

Not applicable.

Code availability

Not applicable.

Author contributions

JH and GC contributed to subject recruitment, sample and data collection, biological analysis, and writing of the manuscript. JY and XW was contributed to sample collection and managed investigational drug. NC contributed to data analysis and manuscript review. JW contributed to collect samples as nurse. JW contributed to clinical observation as a doctor. JZ contributed to management of the clinical trial process.

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He, J., Cao, G., Yu, J. et al. Safety, Tolerability and Pharmacokinetics of Single Ascending and Multiple Oral Doses of Tegoprazan in Healthy Chinese Subjects. Clin Drug Investig 41, 89–97 (2021). https://doi.org/10.1007/s40261-020-00986-4

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  • DOI: https://doi.org/10.1007/s40261-020-00986-4

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