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

Duodenal Ulcer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03050359
• Other study ID #: TAK-438_304
• Secondary ID: U1111-1139-0293C
• Status: Completed
• Phase: Phase 3
• Start date: April 5, 2017
• Est. completion date: July 19, 2019

Study information

• Verified date: May 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 533
• Est. completion date: July 19, 2019
• Est. primary completion date: March 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Duodenal Ulcer
• Ulcer

Intervention

Drug:
• TAK-438
TAK-438 tablets
• Lansoprazole
Lansoprazole capsules
• TAK-438 Placebo
TAK-438 placebo-matching tablets.
• Lansoprazole Placebo
Lansoprazole placebo-matching capsules
• Bismuth-Containing Quadruple Therapy
1 g Amoxicillin, 500 mg clarithromycin and 600 mg bismuth potassium citrate/bismuth tripotassium dicitrate, twice daily (BID).

Locations

Country	Name	City	State
China	Beijing Chao Yang Hospital	Beijing	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Beijing Tong Ren Hospital, Capital Medical University	Beijing	Beijing
China	The Central Hospital of China Aerospace Corporation	Beijing	Beijing
China	The General Hospital of People's Armed Police Forces China	Beijing	Beijing
China	Peking University First Hospital	Beijing,P.R.	Beijing
China	China-Japan Union Hospital of Jilin University	Changchun	Jilin
China	Jilin 4th People'S hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	The 2nd Xiangya Hospital Central South University	Changsha	Hunan
China	The First People's Hospital of Changzhou	Changzhou City	Jiangsu
China	Chenzhou No.1 People's Hospital	Chenzhou	Hunan
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The First People's Hospital of Foshan	Foshan	Guangdong
China	Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	Haikou People's Hospital	Haikou	Hainan
China	1st Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou
China	Zhejiang Hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.	Huangpu Qu	Shanghai
China	Jilin central Hospital	Jilin	Jilin
China	Jingzhou Central Hospital	Jingzhou	Hubei
China	The First Affiliated Hospital of Kunming Medical College	Kunming	Yunnan
China	Jiangxi Nanchang 3rd Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of NanChang University	Nanchang	Jiangxi
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Jiangxi Pingxiang People's Hospital	Pingxiang	Jiangxi
China	Shanghai Tongji Hospital	Shanghai	Shanghai
China	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	General Hospital of Shenyang Military Region	Shenyang	Liaoning
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Shiyan Taihe Hospital	Shiyan	Hebei
China	Jilin Siping Central Hospital	Siping	Jilin
China	Tianjin Medical University Affiliated General Hospital	Tianjin	Tianjin
China	The Second Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology	Wuhan	Hubei
China	Union Hospital of Tongji Medical College of Huazhong Science and Techology University	Wuhan	Hubei
China	Wuhan General Hospital of Guangzhou Military	Wuhan	Hubei
China	Yijishan hospital of Wan nan Medical college	Wuhu	Anhui
China	Wuxi 4th People's Hospital	Wuxi	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The 2nd Hospital of Xi An Jiaotong University	Xi'an	Shanxi
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	People's Hospital of Qinghai Province	Xining	Qinghai
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Changsha Central Hospital	Yuhua	Hunan
China	Zhangzhou Hospital	Zhangzhou	Fujian
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu
Korea, Republic of	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	Dong-A University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Hanyang Univerisy Guri Hospital	Guri-si	Gyeonggi-do
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Wonkwang University Hospital	Iksan-si	Jeollabuk-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	The Catholic University of Korea, Incheon St. Mary's Hospital	Incheon
Korea, Republic of	Chonbuk National University Hospital	Jeonju-si	Jeollabuk-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do
Korea, Republic of	Yonsei University Wonju Severance Christian Hospital	Wonju-si	Gangwon-do
Philippines	Cebu Doctors University Hospital	Cebu City
Philippines	De La Salle University Medical Center	Dasmarinas City, Cavite
Philippines	Davao Doctors Hospital	Davao
Philippines	West Visayas State University Medical Center	Iloilo City
Philippines	Philippine General Hospital	Manila
Philippines	St. Luke's Medical Center Global City	Taguig City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan County

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

China,  Korea, Republic of,  Philippines,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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