Article Text

Download PDFPDF

Original article
Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis
  1. Yinglian Xiao1,
  2. Shutian Zhang2,
  3. Ning Dai3,
  4. Guijun Fei4,
  5. Khean-Lee Goh5,
  6. Hoon Jai Chun6,
  7. Bor-Shyang Sheu7,
  8. Chui Fung Chong8,
  9. Nobuo Funao9,
  10. Wen Zhou10,
  11. Minhu Chen1
  1. 1 Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  2. 2 Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
  3. 3 Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, China
  4. 4 Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
  5. 5 Division of Gastroenterology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  6. 6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Gastrointestinal Medical Instrument Research, Korea University College of Medicine, Seoul, Republic of Korea
  7. 7 Department of Internal Medicine, National Cheng Kung University Hospital and Tainan Hospital, Tainan, Taiwan
  8. 8 Gastroenterology Therapeutic Area Unit, Takeda Development Center Asia, Singapore, Singapore
  9. 9 Takeda Development Center Japan, Takeda Pharmaceutical Company, Osaka, Japan
  10. 10 Department of Clinical Science, Takeda Pharmaceutical Company, Cambridge, Massachusetts, USA
  1. Correspondence to Professor Minhu Chen, Department of Gastroenterology, First affiliated Hospital, Sun Yat-sen University, GuangZhoub 510080, China; chenminhu{at}mail.sysu.edu.cn

Abstract

Objective To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).

Design In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).

Results In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI –3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI –1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI –4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI –5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI –8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI –9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.

Conclusion Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.

Trial registration number NCT02388724.

  • erosive oesophagitis
  • proton pump inhibition
  • gastric acid
  • gastro-oesophageal reflux disease

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

View Full Text

Statistics from Altmetric.com

Footnotes

  • Contributors YX contributed to study design, acquisition and interpretation of data, and critically reviewed and edited the manuscript. SZ contributed to the enrolment of patients, and critically reviewed and edited the manuscript. ND contributed to acquisition of data, revision of the manuscript and final approval of the manuscript. GF contributed to the enrolment of patients and reviewed the manuscript. K-LG contributed to the enrolment of patients, acquisition and analysis of data, and revision of the manuscript. HJC contributed to the acquisition and analysis of data and drafting the final manuscript. B-SS contributed to the enrolment of patients in Taiwan, data analysis and revision of the manuscript. CFC contributed to study design, acquisition and interpretation of the data, and critically reviewed and edited the manuscript. NF contributed to data analysis and interpretation, and critically reviewed and edited the manuscript. WZ contributed to study design, and critically reviewed and edited the manuscript. MC contributed to study design, acquisition and analysis of data, and critically reviewed and edited the manuscript. All authors read and approved the final manuscript, and all authors agree to be accountable for all aspects of the work, which include ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This study was funded by Takeda Pharmaceutical Company. The sponsor was involved in study design, as well as data collection, analysis and interpretation of the data, as well as reviewing the paper and providing funding support for medical writing assistance. The final decision to submit the paper, however, lay with the authors.

  • Competing interests MC received speaker honorarium from Xian Janssen, AstraZeneca China, Ipsen Tianjin, Takeda China and CMS China. CFC is an employee of Takeda Development Center Asia, and stock shareholder in Air Liquide and Abbott Laboratories. NF is an employee of Takeda Pharmaceutical Company, and WZ is a former employee of Takeda Pharmaceutical Company. K-L G received fees for participating in an advisory committee or review panel and speaking and chairing for Takeda Pharmaceutical Company. All other authors declare no competing interests.

  • Patient consent for publication Obtained.

  • Ethics approval The study protocol, informed consent form and other regulation-specified documents were reviewed and approved by the Independent Ethics Committees at Nakakinen Clinic. The study was conducted in accordance with the principles of the World Medical Association Declaration of Helsinki, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the International Conference for Harmonisation Harmonised Tripartite Guideline for Good Clinical Practice, ethical guideline for clinical research, institutional review board regulations, and all applicable local regulations at each participating centre (mainland China, Korea, Taiwan and Malaysia). Written informed consent was obtained from patients before study commencement.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda’s Data Sharing Policy (see https://www.takedaclinicaltrials.com/ for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor’s qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.