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

Phase 3
Completed
Conditions
Gastric Ulcer
Interventions
Drug: TAK-438 Placebo
Drug: Bismuth-Containing Quadruple Therapy
Registration Number
NCT03050307
Lead Sponsor
Takeda
Brief Summary

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

Detailed Description

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

The study will enroll approximately 830 patients.

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

* TAK-438 20 mg

* Lansoprazole 30 mg

Study treatment will depend upon the Helicobacter pylori infection status of the participant, and include bismuth-containing quadruple therapy for the first 2 weeks in H pylori infected (HP+) participants. HP+ participants will be asked to take a TAK- 438 tablet or a lansoprazole capsule twice daily in conjunction with bismuth-containing quadruple therapy for 2 weeks, followed up by a TAK-438 tablet or a lansoprazole capsule once daily for up to 6 weeks. HP- participants will be asked to take a TAK-438 tablet or a lansoprazole capsule once daily for up to 8 weeks.

This multi-center trial will be conducted in China, Korea, Taiwan, and Philippines. The overall time to participate in this study is up to 12 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
234
Inclusion Criteria
  1. Has endoscopic evidence of active gastric ulcer(s) (i.e. mucosal defects with white coating [including cases associated with blood coagula 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 any gastric ulcer of >2 cm in any diameter or with >3 separate gastric ulcers in total as evident by endoscopy within 14 days prior to randomization.

  5. Has a diagnosis of gastric malignancy or a gastric ulcer whose morphology suggested malignancy as evident by endoscopy within 14 days prior to randomization.

  6. Is suspected of having acute gastro-duodenal mucosal lesions (AGDML) as evident by endoscopy within 14 days prior to randomization.

  7. Has a linear ulcer (including a linear ulcer scar) that has been confirmed by endoscopy within 14 days prior to randomization.

  8. Has active postoperative (e.g. endoscopic mucosal resection/endoscopic submucosal dissection) ulcer(s) as confirmed by endoscopy within 14 days prior to randomization.

  9. Has duodenal ulcer that has been confirmed by endoscopy within 14 days prior to randomization.

  10. Has ulcers for which medical therapy alone is not indicated (e.g., perforation, pyloric stenosis, duodenal stenosis, major bleeding).

  11. Has undergone therapeutic upper gastrointestinal (GI) endoscopic therapy (e.g., endoscopic hemostasis or excision including biopsy) within 30 days prior to visit 1.

  12. Has Zollinger-Ellison syndrome or gastric acid hypersecretion or those with a history of gastric acid hypersecretion.

  13. 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 (e.g., abdominal surgery, vagotomy or craniotomy).

  14. 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).

  15. 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) (the participant may be included in the study if he/she is HCV-viral load-RNA-negative).

  16. 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).
  17. 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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TAK-438 20 mgLansoprazole PlaceboHelicobacter Pylori positive (HP+) participants: TAK-438 20 mg tablet, twice daily (BID) along with lansoprazole placebo-matching, capsule BID in addition to bismuth-containing quadruple antibiotic therapy for the first 2 weeks. Following 2 weeks of eradication therapy participants received TAK-438 20 mg QD along with lansoprazole matching placebo 30 mg, capsule QD for up to 6 weeks. HP negative (HP-) participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.
TAK-438 20 mgTAK-438Helicobacter Pylori positive (HP+) participants: TAK-438 20 mg tablet, twice daily (BID) along with lansoprazole placebo-matching, capsule BID in addition to bismuth-containing quadruple antibiotic therapy for the first 2 weeks. Following 2 weeks of eradication therapy participants received TAK-438 20 mg QD along with lansoprazole matching placebo 30 mg, capsule QD for up to 6 weeks. HP negative (HP-) participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.
Lansoprazole 30 mgTAK-438 PlaceboHP+ participants: Lansoprazole 30 mg, capsule, orally, BID and TAK-438 placebo-matching tablet, orally, BID along with bismuth-containing quadruple antibiotic therapy for first 2 weeks. Following 2 weeks participants received Lansoprazole 30 mg, capsule, orally, QD along with TAK-438 placebo-matching tablet, orally, QD for up to 6 weeks. HP- participants: Lansoprazole 30 mg, capsule, orally, QD along with TAK-438 placebo-matching tablet, orally, QD for up to 8 weeks.
Lansoprazole 30 mgBismuth-Containing Quadruple TherapyHP+ participants: Lansoprazole 30 mg, capsule, orally, BID and TAK-438 placebo-matching tablet, orally, BID along with bismuth-containing quadruple antibiotic therapy for first 2 weeks. Following 2 weeks participants received Lansoprazole 30 mg, capsule, orally, QD along with TAK-438 placebo-matching tablet, orally, QD for up to 6 weeks. HP- participants: Lansoprazole 30 mg, capsule, orally, QD along with TAK-438 placebo-matching tablet, orally, QD for up to 8 weeks.
TAK-438 20 mgBismuth-Containing Quadruple TherapyHelicobacter Pylori positive (HP+) participants: TAK-438 20 mg tablet, twice daily (BID) along with lansoprazole placebo-matching, capsule BID in addition to bismuth-containing quadruple antibiotic therapy for the first 2 weeks. Following 2 weeks of eradication therapy participants received TAK-438 20 mg QD along with lansoprazole matching placebo 30 mg, capsule QD for up to 6 weeks. HP negative (HP-) participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.
Lansoprazole 30 mgLansoprazoleHP+ participants: Lansoprazole 30 mg, capsule, orally, BID and TAK-438 placebo-matching tablet, orally, BID along with bismuth-containing quadruple antibiotic therapy for first 2 weeks. Following 2 weeks participants received Lansoprazole 30 mg, capsule, orally, QD along with TAK-438 placebo-matching tablet, orally, QD for up to 6 weeks. HP- participants: Lansoprazole 30 mg, capsule, orally, QD along with TAK-438 placebo-matching tablet, orally, QD for up to 8 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Endoscopically Confirmed Healing of Gastric Ulcers (GUs) at Weeks 4 or 8Week 4 or 8

Endoscopic healing was defined as the disappearance of all white coats associated with GUs confirmed endoscopically.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Endoscopically Confirmed Healing of GU at Week 4Week 4

Endoscopic healing was defined as the disappearance of all white coats associated with GUs confirmed endoscopically.

Percentage of Participants With Post-treatment Resolution of Gastrointestinal Symptoms Associated With GUWeek 2 up to Week 8

The gastrointestinal symptoms included epigastric pain \[postprandial, fasting, nocturnal\], abdominal bloating, nausea/vomiting, heartburn, lack of appetite. The severity of gastrointestinal symptoms associated with GU were recorded as: none = 0, mild = 1, moderate = 2 or severe = 3. The data is reported in categories for percentage of participants with resolution of gastrointestinal symptoms associated with GU.

Percentage of Helicobacter Pylori Infected (HP+) Participants With Successful HP Eradication After 4 or 8 Weeks of Treatment4 weeks post treatment (up to approximately 12 weeks)

HP infection status was determined by 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 data is provided only for HP+ participants. The participant could take 4 or 8 weeks of treatment for GU healing, then additional 4 weeks later, to have the urea breath test (UBT) test to detect HP.

Trial Locations

Locations (81)

The First Affiliated Hospital of Anhui Medical University

🇨🇳

Hefei, Anhui, China

Yijishan hospital of Wan nan Medical college

🇨🇳

Wuhu, Anhui, China

Beijing Chao Yang Hospital

🇨🇳

Beijing, Beijing, China

Beijing Friendship Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

The General Hospital of People's Armed Police Forces China

🇨🇳

Beijing, Beijing, China

The Central Hospital of China Aerospace Corporation

🇨🇳

Beijing, Beijing, China

The Second Affiliated Hospital of Chongqing Medical University

🇨🇳

Chongqing, Chongqing, China

The First Affiliated Hospital of Xiamen University

🇨🇳

Xiamen, Fujian, China

Beijing Tong Ren Hospital, Capital Medical University

🇨🇳

Beijing, Beijing, China

Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA

🇨🇳

Fuzhou, Fujian, China

The First People's Hospital of Foshan

🇨🇳

Foshan, Guangdong, China

Guangdong General Hospital

🇨🇳

Guangzhou, Guangdong, China

Zhangzhou Hospital

🇨🇳

Zhangzhou, Fujian, China

Peking University Shenzhen Hospital

🇨🇳

Shenzhen, Guangdong, China

The Sixth Affiliated Hospital of Sun Yat-Sen University

🇨🇳

Guangzhou, Guangdong, China

Haikou People's Hospital

🇨🇳

Haikou, Hainan, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

🇨🇳

Wuhan, Hubei, China

Shiyan Taihe Hospital

🇨🇳

Shiyan, Hebei, China

Wuhan General Hospital of Guangzhou Military

🇨🇳

Wuhan, Hubei, China

Chenzhou No.1 People's Hospital

🇨🇳

Chenzhou, Hunan, China

Changsha Central Hospital

🇨🇳

Yuhua, Hunan, China

The First People's Hospital of Changzhou

🇨🇳

Changzhou City, Jiangsu, China

Nanjing First Hospital

🇨🇳

Nanjing, Jiangsu, China

Wuxi 4th People's Hospital

🇨🇳

Wuxi, Jiangsu, China

Wuxi People's Hospital

🇨🇳

Wuxi, Jiangsu, China

Affiliated Hospital of Jiangsu University

🇨🇳

Zhenjiang, Jiangsu, China

The First Affiliated Hospital of NanChang University

🇨🇳

Nanchang, Jiangxi, China

Jiangxi Nanchang 3rd Hospital

🇨🇳

Nanchang, Jiangxi, China

Jilin 4th People'S hospital

🇨🇳

Changchun, Jilin, China

Jiangxi Pingxiang People's Hospital

🇨🇳

Pingxiang, Jiangxi, China

Jilin Siping Central Hospital

🇨🇳

Siping, Jilin, China

The First Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

China-Japan Union Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

Jilin central Hospital

🇨🇳

Jilin, Jilin, China

General Hospital of Shenyang Military Region

🇨🇳

Shenyang, Liaoning, China

Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.

🇨🇳

Huangpu Qu, Shanghai, China

People's Hospital of Qinghai Province

🇨🇳

Xining, Qinghai, China

Zhongshan Hospital Fudan University

🇨🇳

Shanghai, Shanghai, China

Tianjin Medical University Affiliated General Hospital

🇨🇳

Tianjin, Tianjin, China

Shanghai Tongji Hospital

🇨🇳

Shanghai, Shanghai, China

The 2nd Hospital of Xi An Jiaotong University

🇨🇳

Xi'an, Shanxi, China

1st Affiliated Hospital of Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, Shanghai, China

The First Affiliated Hospital of Kunming Medical College

🇨🇳

Kunming, Yunnan, China

Zhejiang Hospital

🇨🇳

Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

The Second Affiliated Hospital of Wenzhou Medical College

🇨🇳

Wenzhou, Zhejiang, China

Yonsei University Wonju Severance Christian Hospital

🇰🇷

Wonju-si, Gangwon-do, Korea, Republic of

The Second Affiliated Hospital Zhejiang University School of Medicine

🇨🇳

Hangzhou, China

Korea University Ansan Hospital

🇰🇷

Ansan-si, Gyeonggi-do, Korea, Republic of

The Catholic University of Korea, Bucheon St. Mary s Hospital

🇰🇷

Bucheon-si, Gyeonggi-do, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Gyeonggi-do, Korea, Republic of

Hanyang Univerisy Guri Hospital

🇰🇷

Guri-si, Gyeonggi-do, Korea, Republic of

Dong-A University Hospital

🇰🇷

Busan, Korea, Republic of

Chonbuk National University Hospital

🇰🇷

Jeonju-si, Jeollabuk-do, Korea, Republic of

The Catholic University of Korea, St. Vincent's Hospital

🇰🇷

Suwon-si, Gyeonggi-do, Korea, Republic of

Wonkwang University Hospital

🇰🇷

Iksan-si, Jeollabuk-do, Korea, Republic of

Kyungpook National University Hospital

🇰🇷

Daegu, Korea, Republic of

Yeungnam University Hospital

🇰🇷

Daegu, Korea, Republic of

The Catholic University of Korea, Incheon St. Mary's Hospital

🇰🇷

Incheon, Korea, Republic of

Kangbuk Samsung Hospital

🇰🇷

Seoul, Korea, Republic of

West Visayas State University Medical Center

🇵🇭

Iloilo City, Philippines

Gachon University Gil Medical Center

🇰🇷

Incheon, Korea, Republic of

Severance Hospital, Yonsei University

🇰🇷

Seoul, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Korea, Republic of

St. Luke's Medical Center Global City

🇵🇭

Taguig City, Philippines

China Medical University Hospital

🇨🇳

Taichung, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

Chang Gung Memorial Hospital, Linkou

🇨🇳

Taoyuan County, Taiwan

Jingzhou Central Hospital

🇨🇳

Jingzhou, Hubei, China

Union Hospital of Tongji Medical College of Huazhong Science and Techology University

🇨🇳

Wuhan, Hubei, China

The 2nd Xiangya Hospital Central South University

🇨🇳

Changsha, Hunan, China

General Hospital of Ningxia Medical University

🇨🇳

Yinchuan, Ningxia, China

Davao Doctors Hospital

🇵🇭

Davao, Philippines

Cebu Doctors University Hospital

🇵🇭

Cebu City, Philippines

Tri-Service General Hospital

🇨🇳

Taipei, Taiwan

Chonnam National University Hospital

🇰🇷

Gwangju, Korea, Republic of

De La Salle University Medical Center

🇵🇭

Dasmarinas City, Cavite, Philippines

Philippine General Hospital

🇵🇭

Manila, Philippines

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Peking University First Hospital

🇨🇳

Beijing,P.R., Beijing, China

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