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

Takeda

Status and phase: Completed; Phase 3

Conditions: Duodenal Ulcer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03050359

CTR20170104 (Registry Identifier)

U1111-1139-0293 (Registry Identifier)

TAK-438_304

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 duodenal ulcer.

Full 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.

Enrollment: 533 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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533 participants in 2 patient groups

TAK-438 20 mg

Experimental 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.

Treatment:

Drug: Bismuth-Containing Quadruple Therapy

Drug: Lansoprazole Placebo

Drug: TAK-438

Lansoprazole 30 mg

Experimental group

Description:

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.

Treatment:

Drug: Bismuth-Containing Quadruple Therapy

Drug: TAK-438 Placebo

Drug: Lansoprazole