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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03050307
• Collaborator: (none)
• Enrollment: 234
• Locations: 81
• Arms: 2
• Actual Duration (Months): 37.3
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Ulcer	Drug: TAK-438; Drug: Lansoprazole; Drug: TAK-438 Placebo; Drug: Lansoprazole Placebo; Drug: Bismuth-Containing Quadruple Therapy	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-Blind, Double-Dummy, Phase 3 Study to Evaluate the Efficacy and Safety of Oral TAK-438 20mg Compared to Lansoprazole 30mg Once- or Twice-Daily in the Treatment of Endoscopically Confirmed Gastric Ulcer Subjects With or Without Helicobacter Pylori Infection
• Actual Study Start Date: Apr 17, 2017
• Actual Primary Completion Date: Feb 19, 2020
• Actual Study Completion Date: May 26, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-438 20 mg Helicobacter 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.	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 HP+ 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.	Drug: Lansoprazole; Lansoprazole capsules; Other Names: Prevacid ; Drug: TAK-438 Placebo; TAK-438 placebo-matching tablets; Drug: Bismuth-Containing Quadruple Therapy; 1 g Amoxicillin, 500 mg clarithromycin and 600 mg bismuth potassium citrate/bismuth tripotassium dicitrate, twice daily (BID).

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Endoscopically Confirmed Healing of Gastric Ulcers (GUs) at Weeks 4 or 8 [Week 4 or 8]

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

Secondary Outcome Measures

1. Percentage of Helicobacter Pylori Infected (HP+) Participants With Successful HP Eradication After 4 or 8 Weeks of Treatment [4 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.

2. Percentage of Participants With Endoscopically Confirmed Healing of GU at Week 4 [Week 4]

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

3. Percentage of Participants With Post-treatment Resolution of Gastrointestinal Symptoms Associated With GU [Week 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

17. Creatinine levels: >2 mg/dL (>177 μmol/L).

18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or total bilirubin levels: > upper limit of normal (ULN).

19. 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China	230024
2	Yijishan hospital of Wan nan Medical college	Wuhu	Anhui	China	241001
3	Peking University First Hospital	Beijing,P.R.	Beijing	China	100034
4	Beijing Chao Yang Hospital	Beijing	Beijing	China	100020
5	The General Hospital of People's Armed Police Forces China	Beijing	Beijing	China	100039
6	The Central Hospital of China Aerospace Corporation	Beijing	Beijing	China	100049
7	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
8	Beijing Tong Ren Hospital, Capital Medical University	Beijing	Beijing	China	100730
9	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing	China	40010
10	Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA	Fuzhou	Fujian	China	350025
11	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian	China	361003
12	Zhangzhou Hospital	Zhangzhou	Fujian	China	363000
13	The First People's Hospital of Foshan	Foshan	Guangdong	China	528000
14	Guangdong General Hospital	Guangzhou	Guangdong	China	510080
15	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China	510655
16	Peking University Shenzhen Hospital	Shenzhen	Guangdong	China	518000
17	Haikou People's Hospital	Haikou	Hainan	China	570208
18	Shiyan Taihe Hospital	Shiyan	Hebei	China	442000
19	Jingzhou Central Hospital	Jingzhou	Hubei	China	434020
20	Union Hospital of Tongji Medical College of Huazhong Science and Techology University	Wuhan	Hubei	China	420104
21	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology	Wuhan	Hubei	China	430030
22	Wuhan General Hospital of Guangzhou Military	Wuhan	Hubei	China	430070
23	The 2nd Xiangya Hospital Central South University	Changsha	Hunan	China	410011
24	Chenzhou No.1 People's Hospital	Chenzhou	Hunan	China	432000
25	Changsha Central Hospital	Yuhua	Hunan	China	410018
26	The First People's Hospital of Changzhou	Changzhou City	Jiangsu	China	213003
27	Nanjing First Hospital	Nanjing	Jiangsu	China	210012
28	Wuxi 4th People's Hospital	Wuxi	Jiangsu	China	214062
29	Wuxi People's Hospital	Wuxi	Jiangsu	China	241023
30	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu	China	212001
31	The First Affiliated Hospital of NanChang University	Nanchang	Jiangxi	China	330006
32	Jiangxi Nanchang 3rd Hospital	Nanchang	Jiangxi	China	330009
33	Jiangxi Pingxiang People's Hospital	Pingxiang	Jiangxi	China	337055
34	The First Hospital of Jilin University	Changchun	Jilin	China	130000
35	Jilin 4th People'S hospital	Changchun	Jilin	China	130012
36	China-Japan Union Hospital of Jilin University	Changchun	Jilin	China	130033
37	Jilin central Hospital	Jilin	Jilin	China	132011
38	Jilin Siping Central Hospital	Siping	Jilin	China	136000
39	General Hospital of Shenyang Military Region	Shenyang	Liaoning	China	110016
40	General Hospital of Ningxia Medical University	Yinchuan	Ningxia	China	750004
41	People's Hospital of Qinghai Province	Xining	Qinghai	China	810007
42	Ruijin Hospital, Shanghai Jiaotong Uni. School of Med.	Huangpu Qu	Shanghai	China	200020
43	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200032
44	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China	200092
45	Shanghai Tongji Hospital	Shanghai	Shanghai	China	200442
46	The 2nd Hospital of Xi An Jiaotong University	Xi'an	Shanxi	China	710004
47	Tianjin Medical University Affiliated General Hospital	Tianjin	Tianjin	China	300052
48	The First Affiliated Hospital of Kunming Medical College	Kunming	Yunnan	China	650032
49	1st Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang	China	310003
50	Zhejiang Hospital	Hangzhou	Zhejiang	China	310013
51	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang	China	310016
52	The Second Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang	China	325027
53	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou		China	310009
54	Yonsei University Wonju Severance Christian Hospital	Wonju-si	Gangwon-do	Korea, Republic of	26426
55	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do	Korea, Republic of	15355
56	The Catholic University of Korea, Bucheon St. Mary s Hospital	Bucheon-si	Gyeonggi-do	Korea, Republic of	14647
57	Hanyang Univerisy Guri Hospital	Guri-si	Gyeonggi-do	Korea, Republic of	11923
58	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
59	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do	Korea, Republic of	16247
60	Wonkwang University Hospital	Iksan-si	Jeollabuk-do	Korea, Republic of	54538
61	Chonbuk National University Hospital	Jeonju-si	Jeollabuk-do	Korea, Republic of	54907
62	Dong-A University Hospital	Busan		Korea, Republic of	49201
63	Kyungpook National University Hospital	Daegu		Korea, Republic of	41944
64	Yeungnam University Hospital	Daegu		Korea, Republic of	42415
65	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
66	The Catholic University of Korea, Incheon St. Mary's Hospital	Incheon		Korea, Republic of	21431
67	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
68	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
69	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
70	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	03722
71	Cebu Doctors University Hospital	Cebu City		Philippines	6000
72	De La Salle University Medical Center	Dasmarinas City, Cavite		Philippines	4114
73	Davao Doctors Hospital	Davao		Philippines	8000
74	West Visayas State University Medical Center	Iloilo City		Philippines	5000
75	Philippine General Hospital	Manila		Philippines	1000
76	St. Luke's Medical Center Global City	Taguig City		Philippines	1634
77	China Medical University Hospital	Taichung		Taiwan	40447
78	National Taiwan University Hospital	Taipei		Taiwan	100
79	Taipei Veterans General Hospital	Taipei		Taiwan	11217
80	Tri-Service General Hospital	Taipei		Taiwan	11490
81	Chang Gung Memorial Hospital, Linkou	Taoyuan County		Taiwan	333

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director Clinical Science, Takeda

Study Documents (Full-Text)

• Study Protocol - Dec 21, 2016
• Statistical Analysis Plan - Jun 5, 2020

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03050307
• Other Study ID Numbers: TAK-438_302; U1111-1138-8706; CTR20170100
• First Posted: Feb 10, 2017
• Last Update Posted: Jun 18, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Stomach Ulcer; Ulcer; Lansoprazole; Dexlansoprazole; Bismuth

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 60 investigative sites in China, Korea, and Taiwan from 17 April 2017 to 26 May 2020.
Pre-assignment Detail	Participants with a diagnosis of gastric ulcer (GU) with or without Helicobacter pylori (H. Pylori) infection were randomized in 1:1 ratio to receive TAK-438 and lansoprazole along with placebo (to keep the blind).

Arm/Group Title	TAK-438 20 mg	Lansoprazole 30 mg
Arm/Group Description	Helicobacter 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.	HP+ 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.
Period Title: Overall Study
STARTED	115	119
COMPLETED	107	110
NOT COMPLETED	8	9

Baseline Characteristics

Arm/Group Title	TAK-438 20 mg	Lansoprazole 30 mg	Total
Arm/Group Description	Helicobacter 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- participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.	HP+ 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.	Total of all reporting groups
Overall Participants	115	119	234
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (13.68)	53.5 (13.37)	53.7 (13.50)
Sex: Female, Male (Count of Participants)
Female	29 25.2%	27 22.7%	56 23.9%
Male	86 74.8%	92 77.3%	178 76.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	114 99.1%	119 100%	233 99.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	1 0.9%	0 0%	1 0.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
China	65 56.5%	71 59.7%	136 58.1%
Korea, Republic Of	44 38.3%	42 35.3%	86 36.8%
Taiwan, Province Of China	6 5.2%	6 5%	12 5.1%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	165.4 (7.49)	167.1 (7.96)	166.2 (7.76)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	63.76 (10.743)	66.83 (11.370)	65.32 (11.149)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.25 (3.224)	23.85 (3.255)	23.56 (3.247)
Smoking classification (Count of Participants)
The Participant has Never Smoked	49 42.6%	52 43.7%	101 43.2%
The Participant is a Current Smoker	50 43.5%	51 42.9%	101 43.2%
The Participant is an Ex-smoker	16 13.9%	16 13.4%	32 13.7%
Consumption of Alcohol (Count of Participants)
Drinks Every Day	9 7.8%	6 5%	15 6.4%
Drinks Two Days a Week	20 17.4%	25 21%	45 19.2%
Drinks Two Days a Month	17 14.8%	25 21%	42 17.9%
Never Drinks	69 60%	62 52.1%	131 56%
Caffeine Consumption (Count of Participants)
Yes (>5 Times per Week)	22 19.1%	29 24.4%	51 21.8%
No (Never or <5 Times a Week)	93 80.9%	90 75.6%	183 78.2%
H pylori infection status (13C-UBT) (Count of Participants)
Positive	85 73.9%	89 74.8%	174 74.4%
Negative	29 25.2%	30 25.2%	59 25.2%
Characteristics of GUs: Location I (Count of Participants)
Cardiac Fundus	2 1.7%	2 1.7%	4 1.7%
Upper Gastric Corpus	5 4.3%	4 3.4%	9 3.8%
Middle Gastric Corpus	11 9.6%	7 5.9%	18 7.7%
Lower Gastric Corpus	10 8.7%	13 10.9%	23 9.8%
Gastric Angle	37 32.2%	42 35.3%	79 33.8%
Pyloric Antral Zone	50 43.5%	51 42.9%	101 43.2%
Characteristics of GUs: Location II (Count of Participants)
Anterior Wall	26 22.6%	20 16.8%	46 19.7%
Lesser Curvature	50 43.5%	63 52.9%	113 48.3%
Posterior Wall	19 16.5%	15 12.6%	34 14.5%
Greater Curvature	13 11.3%	15 12.6%	28 12%
Characteristics of GUs: Number of ulcers (number of ulcers) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of ulcers]	1.3 (0.56)	1.2 (0.45)	1.2 (0.51)
Characteristics of GUs: Ulcer morphology (Count of Participants)
Circular	53 46.1%	56 47.1%	109 46.6%
Ellipsoid	47 40.9%	52 43.7%	99 42.3%
Other	15 13%	11 9.2%	26 11.1%
Characteristics of GUs: Ulcer size (Count of Participants)
Miniscule (<5 mm)	0 0%	1 0.8%	1 0.4%
Minor (≥5 mm and <10 mm)	82 71.3%	76 63.9%	158 67.5%
Intermediate (≥10 mm and ≤20 mm)	33 28.7%	42 35.3%	75 32.1%
Time since onset of current ulcers (days) [Median (Full Range) ]
Median (Full Range) [days]	4.0	4.0	4.0
Use of NSAID or LDA (except topical use) at time of onset of ulcer (Count of Participants)
Yes	11 9.6%	8 6.7%	19 8.1%
No	104 90.4%	111 93.3%	215 91.9%
Type of ulcers (Count of Participants)
Primary	96 83.5%	103 86.6%	199 85%
Recurrent	19 16.5%	16 13.4%	35 15%
Time since onset of recurrent ulcers (days) [Median (Full Range) ]
Median (Full Range) [days]	393.0	408.5	393.0

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Endoscopically Confirmed Healing of Gastric Ulcers (GUs) at Weeks 4 or 8
Description	Endoscopic healing was defined as the disappearance of all white coats associated with GUs confirmed endoscopically.
Time Frame	Week 4 or 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) population included all randomized participants who received at least 1 dose of the study drug. Overall number of participants analyzed were participants with data available for analyses.

Arm/Group Title	TAK-438 20 mg	Lansoprazole 30 mg
Arm/Group Description	Helicobacter 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- participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.	HP+ 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.
Measure Participants	112	114
Number (95% Confidence Interval) [percentage of participants]	91.1 79.2%	94.7 79.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 95%; -10.966 to 3.339
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Helicobacter Pylori Infected (HP+) Participants With Successful HP Eradication After 4 or 8 Weeks of Treatment
Description	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.
Time Frame	4 weeks post treatment (up to approximately 12 weeks)

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants who received at least 1 dose of the study drug. Overall number of participants analyzed were participants with data available for analyses.

Arm/Group Title	TAK-438 20 mg	Lansoprazole 30 mg
Arm/Group Description	Helicobacter 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+ 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.
Measure Participants	75	73
Number (95% Confidence Interval) [percentage of participants]	88.0 76.5%	80.8 67.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	If the primary outcome measure was met, then the hypothesis for this outcome measure was that if the lower bound of the 95% CI of the difference was ≥-10%, noninferiority for TAK-438 relative to lansoprazole with regard to H pylori eradication was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 95%; -4.469 to 18.825
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Endoscopically Confirmed Healing of GU at Week 4
Description	Endoscopic healing was defined as the disappearance of all white coats associated with GUs confirmed endoscopically.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants who received at least 1 dose of the study drug. Overall number of participants analyzed were participants with data available for analyses.

Arm/Group Title	TAK-438 20 mg	Lansoprazole 30 mg
Arm/Group Description	Helicobacter 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- participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.	HP+ 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.
Measure Participants	109	112
Number (95% Confidence Interval) [percentage of participants]	76.1 66.2%	82.1 69%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) 95%; -16.644 to 4.741
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Post-treatment Resolution of Gastrointestinal Symptoms Associated With GU
Description	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.
Time Frame	Week 2 up to Week 8

Outcome Measure Data

Analysis Population Description

FAS population included all randomized participants who received at least 1 dose of the study drug. Number analyzed is the number of participants with data available for analysis for the specific category.

Arm/Group Title	TAK-438 20 mg	Lansoprazole 30 mg
Arm/Group Description	Helicobacter 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- participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.	HP+ 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.
Measure Participants	115	119
Epigastric Pain (Postprandial)	78.9 68.6%	80.0 67.2%
Epigastric Pain (Fasting/Nocturnal)	85.0 73.9%	80.5 67.6%
Abdominal Bloating	81.3 70.7%	65.2 54.8%
Nausea/Vomiting	100.0 87%	100.0 84%
Heartburn	95.8 83.3%	85.7 72%
Lack of Appetite	77.8 67.7%	90.0 75.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments	Epigastric Pain (Postprandial)
	Type of Statistical Test	Other
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -25.175 to 23.070
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg
	Comments	Epigastric Pain (Fasting/Nocturnal)
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; -11.907 to 20.931
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments	Abdominal Bloating
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	16.0
	Confidence Interval	(2-Sided) 95%; -11.255 to 43.321
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments	Heartburn
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	10.1
	Confidence Interval	(2-Sided) 95%; -5.109 to 25.348
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	TAK-438 20 mg, Lansoprazole 30 mg
	Comments	Lack of Appetite
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of the 95% CI is ≥-8%, noninferiority for TAK-438 relative to lansoprazole with regard to gastric ulcer healing was declared.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Exact (Clopper-Pearson)
	Estimated Value	-12.2
	Confidence Interval	(2-Sided) 95%; -45.138 to 20.694
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From first dose up to 4 weeks post dose (up to approximately 12 weeks)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	TAK-438 20 mg		Lansoprazole 30 mg
Arm/Group Description	Helicobacter 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- participants: TAK-438 20 mg tablet, (QD) along with lansoprazole matching placebo, 30 mg capsule QD for up to 8 weeks.		HP+ 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.
All Cause Mortality
	TAK-438 20 mg		Lansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/119 (0%)
Serious Adverse Events
	TAK-438 20 mg		Lansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/115 (2.6%)		2/119 (1.7%)
Cardiac disorders
Angina pectoris	0/115 (0%)		1/119 (0.8%)
Infections and infestations
Appendicitis	1/115 (0.9%)		0/119 (0%)
Liver abscess	0/115 (0%)		1/119 (0.8%)
Meningitis	1/115 (0.9%)		0/119 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	1/115 (0.9%)		0/119 (0%)
Other (Not Including Serious) Adverse Events
	TAK-438 20 mg		Lansoprazole 30 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/115 (37.4%)		15/119 (12.6%)
Investigations
Pepsinogen test positive	29/115 (25.2%)		6/119 (5%)
Pepsinogen I increased	23/115 (20%)		8/119 (6.7%)
Blood gastrin increased	24/115 (20.9%)		5/119 (4.2%)
Alanine aminotransferase increased	6/115 (5.2%)		3/119 (2.5%)
Nervous system disorders
Dysgeusia	2/115 (1.7%)		7/119 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.