Comparison of TAK-438 (Vonoprazan) to Lansoprazole in the Treatment of Duodenal Ulcer Participants With or Without Helicobacter Pylori Infection

A Randomized Double-Blind, Double-Dummy, Phase 3 Study to Evaluate the Efficacy and Safety of Oral TAK-438 20 mg Compared to Lansoprazole 30 mg Once- or Twice-Daily in the Treatment of Endoscopically Confirmed Duodenal Ulcer Subjects With or Without Helicobacter Pylori Infection

The purpose of this study is to demonstrate the non-inferior efficacy of TAK-438 versus lansoprazole in the treatment of participants with duodenal ulcer.

Study Overview

• Status: Completed
• Conditions: Duodenal Ulcer
• Intervention / Treatment: Drug: Lansoprazole; Drug: TAK-438; Drug: Lansoprazole Placebo; Drug: Bismuth-Containing Quadruple Therapy; Drug: TAK-438 Placebo

Detailed Description

The drug being tested in this study is called TAK-438. TAK-438 is being tested to treat people who have duodenal ulcers and also may or may not have Helicobacter pylori (HP) infection. This study will look at duodenal ulcer healing and also the elimination of HP in people who take TAK-438 versus lansoprazole. The study will enroll approximately 530 patients.

Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• TAK-438 20 mg
• Lansoprazole 30 mg

HP+ participants will be asked to take a TAK- 438 tablet and a lansoprazole capsule twice daily in conjunction with bismuth-containing quadruple therapy for 2 weeks, followed up by a TAK-438 tablet and a lansoprazole capsule once daily for up to 4 weeks. HP negative (HP-) participants will be asked to take a TAK-438 tablet and a lansoprazole capsule once daily for up to 6 weeks.

This multi-center trial will be conducted China, Korea and Taiwan. The overall time to participate in this study is up to 10 weeks. Participants will make multiple visits plus final visit at 2 weeks or 4 weeks after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 533
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital Zhejiang University School of Medicine
  • Anhui
    • Hefei, Anhui, China, 230024
      • The First Affiliated Hospital of Anhui Medical University
    • Wuhu, Anhui, China, 241001
      • Yijishan hospital of Wan nan Medical college
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100020
      • Beijing Chao Yang Hospital
    • Beijing, Beijing, China, 100039
      • The General Hospital of People's Armed Police Forces China
    • Beijing, Beijing, China, 100049
      • The Central Hospital of China Aerospace Corporation
    • Beijing, Beijing, China, 100730
      • Beijing Tong Ren Hospital, Capital Medical University
    • Beijing,P.R., Beijing, China, 100034
      • Peking University First Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 40010
      • The Second Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
    • Zhangzhou, Fujian, China, 363000
      • Zhangzhou Hospital
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • The First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
    • Shenzhen, Guangdong, China, 518000
      • Peking University Shenzhen Hospital
  • Hainan
    • Haikou, Hainan, China, 570208
      • Haikou People's Hospital
  • Hebei
    • Shiyan, Hebei, China, 442000
      • Shiyan Taihe Hospital
  • Hubei
    • Jingzhou, Hubei, China, 434020
      • Jingzhou Central Hospital
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
    • Wuhan, Hubei, China, 420104
      • Union Hospital of Tongji Medical College of Huazhong Science and Techology University
    • Wuhan, Hubei, China, 430070
      • Wuhan General Hospital of Guangzhou Military
  • Hunan
    • Changsha, Hunan, China, 410011
      • The 2nd Xiangya Hospital Central South University
    • Chenzhou, Hunan, China, 432000
      • Chenzhou No.1 People's Hospital
    • Yuhua, Hunan, China, 410018
      • Changsha Central Hospital
  • Jiangsu
    • Changzhou City, Jiangsu, China, 213003
      • The First People's Hospital Of Changzhou
    • Nanjing, Jiangsu, China, 210012
      • Nanjing First Hospital
    • Wuxi, Jiangsu, China, 214062
      • Wuxi 4th People's Hospital
    • Wuxi, Jiangsu, China, 241023
      • Wuxi People's Hospital
    • Zhenjiang, Jiangsu, China, 212001
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of NanChang University
    • Nanchang, Jiangxi, China, 330009
      • Jiangxi Nanchang 3rd Hospital
    • Pingxiang, Jiangxi, China, 337055
      • Jiangxi Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130033
      • China-Japan Union Hospital of Jilin University
    • Changchun, Jilin, China, 130012
      • Jilin 4th People'S hospital
    • Jilin, Jilin, China, 132011
      • Jilin Central Hospital
    • Siping, Jilin, China, 136000
      • Jilin Siping Central Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • General Hospital of Shenyang Military Region
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Qinghai
    • Xining, Qinghai, China, 810007
      • People's Hospital of Qinghai Province
  • Shanghai
    • Huangpu Qu, Shanghai, China, 200020
      • Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200442
      • Shanghai Tongji Hospital
  • Shanxi
    • Xi'an, Shanxi, China, 710004
      • The 2nd Hospital of Xi An Jiaotong University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University Affiliated General Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • The First Affiliated Hospital of Kunming Medical College
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310013
      • Zhejiang Hospital
    • Hangzhou, Zhejiang, China, 310003
      • 1st Affiliated Hospital of Zhejiang University
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
    • Wenzhou, Zhejiang, China, 325027
      • The Second Affiliated Hospital of Wenzhou Medical College
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Incheon, Korea, Republic of, 21431
    • The Catholic University of Korea, Incheon St. Mary's Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University
  • Gangwon-do
    • Wonju-si, Gangwon-do, Korea, Republic of, 26426
      • Yonsei University Wonju Severance Christian Hospital
  • Gyeonggi-do
    • Ansan-si, Gyeonggi-do, Korea, Republic of, 15355
      • Korea University Ansan Hospital
    • Bucheon-si, Gyeonggi-do, Korea, Republic of, 14647
      • The Catholic University of Korea, Bucheon St. Mary s Hospital
    • Guri-si, Gyeonggi-do, Korea, Republic of, 11923
      • Hanyang Univerisy Guri Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic university of Korea, St. Vincent's Hospital
  • Jeollabuk-do
    • Iksan-si, Jeollabuk-do, Korea, Republic of, 54538
      • Wonkwang University Hospital
    • Jeonju-si, Jeollabuk-do, Korea, Republic of, 54907
      • Chonbuk National University Hospital
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Doctors University Hospital
  • Dasmarinas City, Cavite, Philippines, 4114
    • De La Salle University Medical Center
  • Davao, Philippines, 8000
    • Davao Doctors Hospital
  • Iloilo City, Philippines, 5000
    • West Visayas State University Medical Center
  • Manila, Philippines, 1000
    • Philippine General Hospital
  • Taguig City, Philippines, 1634
    • St. Luke's Medical Center Global City
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 11490
    • Tri-Service General Hospital
  • Taoyuan County, Taiwan, 333
    • Chang Gung Memorial Hospital, Linkou

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Has endoscopic evidence of active duodenal ulcer(s) (i.e., mucosal defects with white coating [including cases associated with blood coagulation as long as there is no active bleeding]) measuring 5 mm or larger in longest diameter within 14 days prior to randomization.

Exclusion Criteria:

1. Has received TAK-438 in a previous clinical study or as a therapeutic agent.
2. Has a history or clinical manifestations of significant central nervous system (CNS), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine or hematological disease that, in the opinion of the investigator, would confound the study results or compromise participant safety.
3. Has been treated with Helicobacter pylori eradication therapy within 30 days prior to study treatment.
4. Has a diagnosis of duodenal malignancy or a duodenal ulcer whose morphology suggested malignancy as evident by endoscopy within 14 days prior to randomization.
5. Is suspected of having acute gastro-duodenal mucosal lesions (AGDML) as evident by endoscopy within 14 days prior to randomization.
6. Has a linear ulcer (including a linear ulcer scar) that has been confirmed as evident by endoscopy within 14 days prior to randomization.
7. Has active postoperative (eg, endoscopic mucosal resection / endoscopic submucosal dissection) ulcer(s) as confirmed by endoscopy within 14 days prior to randomization.
8. Has gastric ulcer that has been confirmed by endoscopy within 14 days prior to randomization.
9. Has ulcers for which medical therapy alone is not indicated (eg, perforation, pyloric stenosis, duodenal stenosis, major bleeding).
10. Has undergone therapeutic upper gastrointestinal (GI) endoscopic therapy (eg, endoscopic hemostasis or excision including biopsy) within 30 days prior to visit 1.
11. Has Zollinger-Ellison syndrome or gastric acid hypersecretion or those with a history of gastric acid hypersecretion.
12. Has undergone major surgical procedures within 30 days prior to Visit 1 or are scheduled to undergo surgical procedures that may affect gastric acid secretion (eg, abdominal surgery, vagotomy or craniotomy).
13. Has a history of malignancy or was treated for malignancy within 5 years before the start of the visit 1 (the participant may be included in the study if he/she has cured cutaneous basal cell carcinoma or cervical carcinoma in situ).
14. Has a known acquired immunodeficiency syndrome (AIDS) or hepatitis infection, including hepatitis virus carriers (hepatitis B surface-antigen [HBsAg] - or hepatitis C virus (HCV)-antibody-positive) (the participant may be included in the study if he/she is HCV-viral load-RNA-negative).

15. Laboratory tests performed prior to randomization revealed any of the following abnormalities in the participant:

    1. Creatinine levels: >2 mg/dL (>177 μmol/L).
    2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or total bilirubin levels: > upper limit of normal (ULN).
16. Has hypersensitivity to TAK-438, proton pump inhibitors (PPIs), bismuth, clarithromycin, or amoxicillin. Skin testing may be performed according to local standard practice (for HP+ participants only).

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: TAK-438 20 mg; H. pylori negative (HP -) participants: TAK-438 20 mg, tablets, orally, once daily (QD) and lansoprazole placebo-matching capsules, orally, QD for up to 6 weeks. H. pylori positive (HP +) participants: TAK-438 20 mg, tablets, orally, twice daily (BID) and lansoprazole placebo-matching capsules, orally, BID for first 2 weeks along with Bismuth-Containing Quadruple Therapy followed byTAK-438 20 mg, tablets, orally, QD and lansoprazole placebo-matching capsules, orally, QD for up to 4 weeks.	Drug: TAK-438; TAK-438 tablets; Other Names: Vonoprazan; Drug: Lansoprazole Placebo; Lansoprazole placebo-matching capsules; Drug: Bismuth-Containing Quadruple Therapy; 1 g Amoxicillin, 500 mg clarithromycin and 600 mg bismuth potassium citrate/bismuth tripotassium dicitrate, twice daily (BID).
Experimental: Lansoprazole 30 mg; H. pylori negative (HP -) participants: lansoprazole 30 mg, capsules, orally, QD and TAK-438 placebo-matching tablets, orally, QD for up to 6 weeks. HP + participants: lansoprazole 30 mg, capsules, orally, BID and TAK-438 placebo-matching tablets, orally, BID for first 2 weeks along with Bismuth-Containing Quadruple Therapy followed by lansoprazole 30 mg, capsules, orally, QD and TAK-438 placebo-matching tablets, orally, BID for up to 4 weeks.	Drug: Lansoprazole; Lansoprazole capsules; Other Names: Prevacid; Drug: Bismuth-Containing Quadruple Therapy; 1 g Amoxicillin, 500 mg clarithromycin and 600 mg bismuth potassium citrate/bismuth tripotassium dicitrate, twice daily (BID).; Drug: TAK-438 Placebo; TAK-438 placebo-matching tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Endoscopically Confirmed Healing of Duodenal Ulcers	Endoscopic healing was defined as the disappearance of all white coats associated with duodenal ulcers as confirmed endoscopically.	Week 4 or Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Helicobacter Pylori Infected (HP+) Participants With Successful HP Eradication After 4 or 6 Weeks of 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.	4 weeks post treatment (Up to 10 weeks)
Percentage of Participants With Endoscopically Confirmed Healing of Duodenal Ulcer at Week 4	Endoscopic healing is defined as the disappearance of all white coats associated with duodenal ulcers as confirmed endoscopically.	Week 4
Percentage of Participants With Posttreatment Resolution of Gastrointestinal Symptoms Associated With Duodenal Ulcer at Weeks 2 Through 6	The percentage of participants with resolution of various gastrointestinal symptoms are reported as categories. Gastrointestinal symptoms included epigastric pain (postprandial, fasting, nocturnal), abdominal bloating, nausea/vomiting, heartburn and lack of appetite. The severity of subjective symptoms of erosive esophagitis were recorded as: none = 0, mild = 1, moderate = 2 or severe = 3.	Week 2 up to Week 6

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Actual): March 19, 2019
• Study Completion (Actual): July 19, 2019

Study Registration Dates

• First Submitted: February 8, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (Actual): February 10, 2017

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: May 27, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Drug therapy; Gastrointestinal Diseases; Digestive System Diseases; Enzyme Inhibitors; Lansoprazole; Proton Pump Inhibitors; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Anti-Ulcer Agents
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Ulcer; Duodenal Ulcer; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antacids; Dexlansoprazole; Lansoprazole; Bismuth
• Other Study ID Numbers: TAK-438_304; U1111-1139-0293 (Registry Identifier: WHO); CTR20170104 (Registry Identifier: CFDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see 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.

Drug and device information, study documents

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