Clincosm LogoSign in Get a demo

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

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT03050359
Collaborator
(none)
533
Enrollment
81
Locations
2
Arms
27.4
Actual Duration (Months)
6.6
Patients Per Site
0.2
Patients Per Site Per Month

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 duodenal ulcer.

Condition or Disease Intervention/Treatment Phase
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 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 Design

Study Type:
Interventional
Actual Enrollment :
533 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 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
Actual Study Start Date :
Apr 5, 2017
Actual Primary Completion Date :
Mar 19, 2019
Actual Study Completion Date :
Jul 19, 2019

Arms and Interventions

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: 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 Duodenal Ulcers [Week 4 or Week 6]

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

    Secondary Outcome Measures

    1. Percentage of Helicobacter Pylori Infected (HP+) Participants With Successful HP Eradication After 4 or 6 Weeks of Treatment [4 weeks post treatment (Up to 10 weeks)]

      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.

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

      Endoscopic healing is defined as the disappearance of all white coats associated with duodenal ulcers as confirmed endoscopically.

    3. Percentage of Participants With Posttreatment Resolution of Gastrointestinal Symptoms Associated With Duodenal Ulcer at Weeks 2 Through 6 [Week 2 up to Week 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.

    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 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:

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

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

    18. 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: Medical Director Clinical Science, Takeda

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT03050359
    Other Study ID Numbers:
    • TAK-438_304
    • U1111-1139-0293
    • CTR20170104
    First Posted:
    Feb 10, 2017
    Last Update Posted:
    Jun 12, 2020
    Last Verified:
    May 1, 2020
    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
    Gastrointestinal Diseases
    Digestive System Diseases
    Lansoprazole
    Anti-Ulcer Agents
    Gastrointestinal Agents
    Proton Pump Inhibitors
    Enzyme Inhibitors
    Molecular Mechanisms of Pharmacological Action
    Additional relevant MeSH terms:
    Duodenal Ulcer
    Ulcer
    Lansoprazole
    Dexlansoprazole
    Bismuth

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 52 investigative sites in China, Korea, and Taiwan from 05 April 2017 to 19 July 2019.
    Pre-assignment Detail Participants with or without diagnosis of Helicobacter pylori (H. Pylori) Infection were enrolled and randomly assigned in 1:1 ratio to receive either TAK-438 20 mg or lansoprazole 30 mg along with matching placebo (to keep the blind).
    Arm/Group Title TAK-438 20 mg Lansoprazole 30 mg
    Arm/Group Description 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. 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.
    Period Title: Overall Study
    STARTED 265 268
    COMPLETED 248 248
    NOT COMPLETED 17 20

    Baseline Characteristics

    Arm/Group Title TAK-438 20 mg Lansoprazole 30 mg Total
    Arm/Group Description HP - participants: TAK-438 20 mg, tablets, orally, once daily (QD) and lansoprazole placebo-matching capsules, orally, QD for up to 6 weeks. 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. 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. Total of all reporting groups
    Overall Participants 265 268 533
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    42.0
    (12.18)
    41.4
    (12.89)
    41.7
    (12.53)
    Sex: Female, Male (Count of Participants)
    Female
    99
    37.4%
    92
    34.3%
    191
    35.8%
    Male
    166
    62.6%
    176
    65.7%
    342
    64.2%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    265
    100%
    268
    100%
    533
    100%
    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
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    China
    252
    95.1%
    255
    95.1%
    507
    95.1%
    Korea, Republic Of
    10
    3.8%
    8
    3%
    18
    3.4%
    Taiwan, Province Of China
    3
    1.1%
    5
    1.9%
    8
    1.5%
    Height (centimeter (cm)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [centimeter (cm)]
    166.1
    (8.21)
    167.1
    (8.09)
    166.6
    (8.16)
    Weight (kilograms (kg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms (kg)]
    63.45
    (12.342)
    64.00
    (11.383)
    63.72
    (11.860)
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    22.87
    (3.365)
    22.83
    (3.181)
    22.85
    (3.270)
    Smoking Classification (Count of Participants)
    The Participant Has Never Smoked
    164
    61.9%
    165
    61.6%
    329
    61.7%
    The Participant Is a Current Smoker
    86
    32.5%
    84
    31.3%
    170
    31.9%
    The Participant Is an Ex-smoker
    15
    5.7%
    19
    7.1%
    34
    6.4%
    Consumption of Alcohol (Count of Participants)
    Drink Everyday
    6
    2.3%
    2
    0.7%
    8
    1.5%
    Drink a Couple of Days Per Week
    20
    7.5%
    21
    7.8%
    41
    7.7%
    Drink a Couple of Days Per Month
    48
    18.1%
    58
    21.6%
    106
    19.9%
    Never Drink
    191
    72.1%
    187
    69.8%
    378
    70.9%
    Consumption of Caffeine (Count of Participants)
    Yes (More Than 5 Times Per Week)
    23
    8.7%
    16
    6%
    39
    7.3%
    No (Never Drink or Less Than 5 Times Per Week)
    242
    91.3%
    252
    94%
    494
    92.7%
    History of H.pylori Eradication Therapy (Count of Participants)
    Yes (Therapy Received Ever)
    16
    6%
    5
    1.9%
    21
    3.9%
    No (Never Receive Any Therapy)
    249
    94%
    263
    98.1%
    512
    96.1%
    H. pylori Infection Status (Count of Participants)
    Positive
    226
    85.3%
    229
    85.4%
    455
    85.4%
    Negative
    37
    14%
    38
    14.2%
    75
    14.1%
    Characteristics of Current Duodenal Ulcers (DU): Location (Count of Participants)
    Superior Part (Including Bulb)
    262
    98.9%
    266
    99.3%
    528
    99.1%
    Descending Part
    3
    1.1%
    1
    0.4%
    4
    0.8%
    Characteristics of Current DU: Mean Number of Ulcers Found (number of ulcers) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [number of ulcers]
    1.2
    (0.48)
    1.3
    (0.54)
    1.2
    (0.51)
    Characteristics of Current DU: Ulcer Morphology (Count of Participants)
    Circular
    110
    41.5%
    117
    43.7%
    227
    42.6%
    Ellipsoidal
    109
    41.1%
    107
    39.9%
    216
    40.5%
    Other
    46
    17.4%
    44
    16.4%
    90
    16.9%
    Characteristics of Current DU: Ulcer Size (Count of Participants)
    Minuscule (<5 mm)
    0
    0%
    1
    0.4%
    1
    0.2%
    Minor (>=5 mm/<10 mm)
    183
    69.1%
    188
    70.1%
    371
    69.6%
    Intermediate (>=10 mm/<=20 mm)
    81
    30.6%
    78
    29.1%
    159
    29.8%
    Large (>20 mm/<30 mm)
    1
    0.4%
    0
    0%
    1
    0.2%
    Giant (>=30 mm)
    0
    0%
    1
    0.4%
    1
    0.2%
    History of DU: Time Since Onset of Current Ulcers (days) [Median (Full Range) ]
    Median (Full Range) [days]
    1.0
    1.0
    1.0
    Use of NSAIDs or Low-dose Aspirin at the Time of Ulcer Onset (Count of Participants)
    Yes
    1
    0.4%
    2
    0.7%
    3
    0.6%
    No
    264
    99.6%
    266
    99.3%
    530
    99.4%
    History of DU: Type of Ulcers (Count of Participants)
    Primary
    230
    86.8%
    227
    84.7%
    457
    85.7%
    Recurrent
    35
    13.2%
    41
    15.3%
    76
    14.3%
    Time Since Onset of Recurrent Ulcers (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    1149.3
    (910.72)
    999.7
    (828.57)
    1068.7
    (859.12)

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS) included all participants who were randomized and 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 HP - participants: TAK-438 20 mg, tablets, orally, once daily (QD) and lansoprazole placebo-matching capsules, orally, QD for up to 6 weeks. 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. 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.
    Measure Participants 254 255
    Number (95% Confidence Interval) [percentage of participants]
    96.9
    36.6%
    96.5
    36%
    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 was ≥-6%, the DU healing rate for TAK-438 was considered to be noninferior to that seen with lansoprazole.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Exact (Clopper-Pearson)
    Estimated Value 0.4
    Confidence Interval (2-Sided) 95%
    -2.998 to 3.791
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Helicobacter Pylori Infected (HP+) Participants With Successful HP Eradication After 4 or 6 Weeks of Treatment
    Description 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.
    Time Frame 4 weeks post treatment (Up to 10 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants from FAS, included all participants who were randomized and received at least 1 dose of the study drug with H pylori positive status at Baseline with data available for analyses.
    Arm/Group Title TAK-438 20 mg Lansoprazole 30 mg
    Arm/Group Description 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. 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.
    Measure Participants 211 204
    Number (95% Confidence Interval) [percentage of participants]
    91.5
    34.5%
    86.8
    32.4%
    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 was ≥-10%, the HP eradication rate for TAK-438 was considered to be noninferior to that seen with lansoprazole.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Exact (Clopper-Pearson)
    Estimated Value 4.7
    Confidence Interval (2-Sided) 95%
    -1.281 to 10.690
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With Endoscopically Confirmed Healing of Duodenal Ulcer at Week 4
    Description Endoscopic healing is defined as the disappearance of all white coats associated with duodenal ulcers as confirmed endoscopically.
    Time Frame Week 4

    Outcome Measure Data

    Analysis Population Description
    FAS included all participants who were randomized and 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 HP - participants: TAK-438 20 mg, tablets, orally, once daily (QD) and lansoprazole placebo-matching capsules, orally, QD for up to 6 weeks. 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. 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.
    Measure Participants 249 251
    Number (95% Confidence Interval) [percentage of participants]
    89.2
    33.7%
    88.4
    33%
    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 was ≥-6%, the DU healing rate for TAK-438 was considered to be noninferior to that seen with lansoprazole.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Exact (Clopper-Pearson)
    Estimated Value 0.7
    Confidence Interval (2-Sided) 95%
    -4.901 to 6.319
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With Posttreatment Resolution of Gastrointestinal Symptoms Associated With Duodenal Ulcer at Weeks 2 Through 6
    Description 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.
    Time Frame Week 2 up to Week 6

    Outcome Measure Data

    Analysis Population Description
    FAS included all participants who were randomized and received at least 1 dose of the study drug. Number analyzed is number of participants analyzed for the particular category (symptom).
    Arm/Group Title TAK-438 20 mg Lansoprazole 30 mg
    Arm/Group Description HP - participants: TAK-438 20 mg, tablets, orally, once daily (QD) and lansoprazole placebo-matching capsules, orally, QD for up to 6 weeks. 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. 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.
    Measure Participants 263 268
    Epigastric Pain (Postprandial)
    87.7
    33.1%
    91.8
    34.3%
    Epigastric Pain (Fasting/Nocturnal)
    91.7
    34.6%
    90.1
    33.6%
    Abdominal Bloating
    83.3
    31.4%
    87.3
    32.6%
    Nausea/Vomiting
    85.2
    32.2%
    94.4
    35.2%
    Heartburn
    100.0
    37.7%
    95.5
    35.6%
    Lack of Appetite
    90.9
    34.3%
    100.0
    37.3%
    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
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value -4.1
    Confidence Interval (2-Sided) 95%
    -15.579 to 7.344
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection TAK-438 20 mg, Lansoprazole 30 mg
    Comments Epigastric Pain (Fasting/Nocturnal)
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 1.6
    Confidence Interval (2-Sided) 95%
    -5.230 to 8.422
    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 Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value -4.0
    Confidence Interval (2-Sided) 95%
    -17.338 to 9.401
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection TAK-438 20 mg, Lansoprazole 30 mg
    Comments Nausea/Vomiting
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value -9.3
    Confidence Interval (2-Sided) 95%
    -26.334 to 7.815
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection TAK-438 20 mg, Lansoprazole 30 mg
    Comments Heartburn
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value 4.5
    Confidence Interval (2-Sided) 95%
    -4.159 to 13.250
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection TAK-438 20 mg, Lansoprazole 30 mg
    Comments Lack of Appetite
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in percentages
    Estimated Value -9.1
    Confidence Interval (2-Sided) 95%
    -21.104 to 2.922
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Up to Week 10 (Up to 6 weeks of treatment)
    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 HP - participants: TAK-438 20 mg, tablets, orally, once daily (QD) and lansoprazole placebo-matching capsules, orally, QD for up to 6 weeks. 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. 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.
    All Cause Mortality
    TAK-438 20 mg Lansoprazole 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/263 (0%) 0/268 (0%)
    Serious Adverse Events
    TAK-438 20 mg Lansoprazole 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/263 (0.4%) 3/268 (1.1%)
    Gastrointestinal disorders
    Duodenal ulcer haemorrhage 1/263 (0.4%) 0/268 (0%)
    Infections and infestations
    Pneumonia 0/263 (0%) 1/268 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder transitional cell carcinoma 0/263 (0%) 1/268 (0.4%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 0/263 (0%) 1/268 (0.4%)
    Other (Not Including Serious) Adverse Events
    TAK-438 20 mg Lansoprazole 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 162/263 (61.6%) 113/268 (42.2%)
    Infections and infestations
    Upper respiratory tract infection 21/263 (8%) 37/268 (13.8%)
    Investigations
    Pepsinogen test positive 124/263 (47.1%) 28/268 (10.4%)
    Pepsinogen I increased 92/263 (35%) 37/268 (13.8%)
    Blood gastrin increased 97/263 (36.9%) 20/268 (7.5%)
    Protein urine present 20/263 (7.6%) 11/268 (4.1%)
    Alanine aminotransferase increased 12/263 (4.6%) 17/268 (6.3%)
    Nervous system disorders
    Dysgeusia 21/263 (8%) 22/268 (8.2%)

    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.

    Results Point of Contact

    Name/Title Medical Director
    Organization Takeda
    Phone +1-877-825-3327
    Email trialdisclosures@takeda.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT03050359
    Other Study ID Numbers:
    • TAK-438_304
    • U1111-1139-0293
    • CTR20170104
    First Posted:
    Feb 10, 2017
    Last Update Posted:
    Jun 12, 2020
    Last Verified:
    May 1, 2020