A Study to Evaluate the Efficacy and Safety of Bismuth-Containing Quadruple Therapy With Oral Vonoprazan (TAK-438) 20 mg Compared to Esomeprazole 20 mg Twice Daily in Paticipants With Helicobacter Pylori Infection

A Randomized Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Bismuth-Containing Quadruple Therapy With Oral TAK-438 20 mg Compared to Esomeprazole 20 mg Twice Daily in Subjects With Helicobacter Pylori Infection

The purpose of this study is to evaluate the efficacy of helicobacter pylori (HP) eradication with bismuth-containing quadruple therapy with vonoprazan versus esomeprazole in all HP-positive participants.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori
• Intervention / Treatment: Drug: Vonoprazan; Drug: Amoxicillin; Drug: Clarithromycin; Drug: Bismuth Potassium citrate; Drug: Esomeprazole

Detailed Description

The drug being tested in this study is called vonoprazan (TAK-438). Vonoprazan is being tested to treat people who have helicobacter pylori infection.

The study is planned to enroll 425 patients at the beginning and will enroll a maximum of approximately 510 patients based on the interim analysis results. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

Vonoprazan 20 mg

Esomeprazole 20 mg

All participants will be asked to take one tablet in combination with bismuth containing quadruple therapy (amoxicillin, clarithromycin and bismuth potassium citrate) twice at the same time each day throughout the study.

This multi-center trial will be conducted in China. The overall time to participate in this study is 10 weeks. Participants will make multiple visits to the clinic, and 28 days after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100000
      • Friendship Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fuzhou General hospital of Nanjing Military Command
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
    • Xiamen, Fujian, China, 361004
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • The First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
  • Hainan
    • Haikou, Hainan, China, 570208
      • Haikou people's Hosptial
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410011
      • The second Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University, Digestive Department
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • The First People's Hospital Of Changzhou
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China, 210029
      • Nanjing First Hospital
    • Yangzhou, Jiangsu, China, 225001
      • Northern Jiangsu People's Hospital
    • Yangzhou, Jiangsu, China, 225000
      • Yangzhou First People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • The Third Hospital of Nanchang
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Digestive Department
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China, 200000
      • Shanghai East Hospital
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Xi'an, Shanxi, China, 710004
      • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • First Affiliated Hospital of Xinjiang Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The Second Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Helicobacter pylori (HP)-positive participants as determined by ^13C-urea breath test (^13C-UBT) at the start of the study (Visit 1 [screening]) and who require HP eradication in Physician judgment.

Exclusion Criteria:

1. Participant had any of the following conditions at the start of the study (Visit 1, screening): acute upper gastrointestinal bleeding, active gastric ulcer (GU) or duodenal ulcer (DU) characterized by defective mucos with white coating (with or without adherent blood clots) 3 mm or more in size, acute gastric mucosal lesion (AGML), or acute duodenal mucosal lesion (ADML). However, participants with gastritis, gastric or duodenal erosion are permitted to participate.
2. Participants with Zollinger-Ellison syndrome or gastric acid hypersecretion or those with a history of gastric acid hypersecretion.
3. Participant has a history of malignancy or was treated for malignancy within 5 years before the start of the screening visit (the participant may be included in the study if he/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ).
4. Participant has a known acquired immunodeficiency syndrome or hepatitis infection, including hepatitis virus carriers (hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV]- antibody-positive).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vonoprazan 20 mg; Vonoprazan 20 mg, tablets, orally, twice daily given in combination with bismuth containing quadruple therapy (amoxicillin 1 gm, capsules, clarithromycin 500 mg, tablets, and bismuth potassium citrate 600 mg) orally, twice daily for up to 2 weeks.	Drug: Vonoprazan; Vonoprazan Tablets; Other Names: TAK-438; Drug: Amoxicillin; Amoxicillin Capsules; Drug: Clarithromycin; Clarithromycin Tablets; Drug: Bismuth Potassium citrate; Bismuth Potassium citrate
Active Comparator: Esomeprazole 20 mg; Esomeprazole 20 mg, tablets, orally, twice daily given in combination with bismuth containing quadruple therapy (amoxicillin 1 gm, capsules, clarithromycin 500 mg, tablets, and bismuth potassium citrate 600 mg) orally, twice daily for up to 2 weeks.	Drug: Amoxicillin; Amoxicillin Capsules; Drug: Clarithromycin; Clarithromycin Tablets; Drug: Bismuth Potassium citrate; Bismuth Potassium citrate; Drug: Esomeprazole; Esomeprazole Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Helicobacter Pylori Positive (HP+) Participants With Successful HP Eradication at Week 4 Post-Treatment	HP infection status was determined by ^13C Urea Breath Test (^13C-UBT). The urea breath test is used to detect infection with HP, a bacteria associated with stomach ulcers, by testing individual breath samples in a central laboratory. The percentages are rounded off to report the nearest ten.	Week 4 post-treatment

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director Clinical Science, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2020
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 25, 2021

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Natriuretic Agents; Anti-Bacterial Agents; Diuretics; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Respiratory System Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Expectorants; Antacids; Amoxicillin; Clarithromycin; Esomeprazole; Bismuth; Potassium Citrate
• Other Study ID Numbers: Vonoprazan-3002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No