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

Takeda

Status and phase: Completed; Phase 3

Conditions: Gastric Ulcer

Treatments: Drug: TAK-438; Drug: Lansoprazole; Drug: Lansoprazole Placebo; Drug: Bismuth-Containing Quadruple Therapy; Drug: TAK-438 Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03050307

U1111-1138-8706 (Other Identifier)

CTR20170100 (Registry Identifier)

TAK-438_302

Details and patient eligibility

About

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.

Full 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.

Enrollment: 234 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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234 participants in 2 patient groups

TAK-438 20 mg

Experimental 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.

Treatment:

Drug: Bismuth-Containing Quadruple Therapy

Drug: TAK-438

Drug: Lansoprazole Placebo

Lansoprazole 30 mg

Experimental group

Description:

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.

Treatment:

Drug: TAK-438 Placebo

Drug: Bismuth-Containing Quadruple Therapy

Drug: Lansoprazole