Efficacy of TAK-438, Amoxicillin and Clarithromycin in the First Line Eradication of H. Pylori

A Phase 3, Randomized, Double-Blind, Double Dummy, Multicenter, Parallel Group Comparison Study to Evaluate Efficacy and Safety of a Triple Therapy With TAK-438, Amoxicillin and Clarithromycin by Comparison With a Triple Therapy With AG-1749 (Lansoprazole), Amoxicillin and Clarithromycin for the First Line Eradication of H.Pylori

The purpose of this study is to confirm the efficacy of triple therapy with TAK-438, Amoxicillin and Clarithromycin, twice daily (BID) by demonstrating its non-inferiority to triple therapy with Lansoprazole, Amoxicillin and Clarithromycin in H. pylori-positive patients with scarred gastric or duodenal ulcers.

Study Overview

• Status: Completed
• Conditions: H. Pylori Infection
• Intervention / Treatment: Drug: Clarithromycin; Drug: Lansoprazole; Drug: TAK-438; Drug: Amoxicillin

• Study Type: Interventional
• Enrollment (Actual): 650
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Abiko-shi, Chiba, Japan
    • Kashiwa-shi, Chiba, Japan
  • Fukui
    • Fukui-shi, Fukui, Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
  • Hokkaido
    • Ishikari-shi, Hokkaido, Japan
    • Sapporo-shi, Hokkaido, Japan
  • Hyogo
    • Kobe-shi, Hyogo, Japan
    • Nishinomiya-shi, Hyogo, Japan
  • Kagawa
    • Marugame-shi, Kagawa, Japan
    • Takamatsu-shi, Kagawa, Japan
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan
  • Kanagawa
    • Ebina-shi, Kanagawa, Japan
    • Yokohama-shi, Kanagawa, Japan
  • Kumamoto
    • Yatsushiro-shi, Kumamoto, Japan
  • Kyoto
    • Kyoto-shi, Kyoto, Japan
  • Oita
    • Oita-shi, Oita, Japan
  • Osaka
    • Hirakata-shi, Osaka, Japan
    • Osaka-shi, Osaka, Japan
    • Sakai-shi, Osaka, Japan
    • Suita-shi, Osaka, Japan
    • Takatsuki-shi, Osaka, Japan
    • Toyonaka-shi, Osaka, Japan
  • Saga
    • Saga-shi, Saga, Japan
  • Saitama
    • Kumagaya-shi, Saitama, Japan
    • Tokorozawa-shi, Saitama, Japan
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan
  • Tokyo
    • Adachi-ku, Tokyo, Japan
    • Chiyoda-ku, Tokyo, Japan
    • Hachioji-shi, Tokyo, Japan
    • Kokubunji-shi, Tokyo, Japan
    • Nishi-tokyo-shi, Tokyo, Japan
    • Oota-ku, Tokyo, Japan
    • Ota-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan
    • Shibuya-ku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants must be H. pylori-positive patients at baseline (Visit 1)

2. Participants must be endoscopically confirmed to have scarred gastric ulcer or duodenal ulcer at baseline (Visit 1).

   However, if a history of ulcers is confirmed by the medical interview or previous medical record, Participants whose gastric ulcer scar or duodenal ulcer scar has disappeared may be included in the study.

3. Outpatient (including inpatient for examination)

Exclusion Criteria:

1. Participants who have received H.pylori eradication treatment

2. Participants who have either acute upper gastrointestinal bleeding, gastric ulcer [mucosal defect (with white coating including clot adherence) of 3 mm or larger in size], duodenal ulcer [mucosal defect (with white coating including clot adherence) of 3 mm or larger in size], acute gastric mucosal lesion (AGML), or acute duodenal mucosal lesion (ADML) on endoscopic examination at baseline (Visit 1).

   However, participants with gastric erosion or duodenal erosion may be included in the study.

3. Participants who have received or who are scheduled to undergo surgery which affects gastric acid secretion (ex, resection of upper gastrointestinal tract, vagotomy, etc)
4. Participants who cannot be treated with medicinal treatment (ex, perforation, pyloric stenosis or large hemorrhage, etc)
5. Participants with a previous or current history of Zollinger-Ellison syndrome, or other gastric acid hypersecretion disorders
6. Participants with hepatic or renal impairment receiving treatment with colchicines
7. Participants who have a history of hypersensitivity or allergy to TAK-438 (including its excipients), PPIs, penicillin antibiotics, macrolide antibiotics, or antitrichomonal agents
8. Participants with infectious mononucleosis
9. Participants with an organic disease of the brain or spinal cord

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-438 20 mg BID; TAK-438 20 mg, tablets, orally, twice daily for 1 week Lansoprazole placebo-matching capsules, orally, twice daily for 1 week Amoxicillin 750 mg, capsules, orally, twice daily for 1 week Clarithromycin 200 or 400 mg, tablets, orally, twice daily for 1 week	Drug: Clarithromycin; Drug: TAK-438; Drug: Amoxicillin
Experimental: Lansoprazole 30 mg BID; TAK-438 placebo-matching tablets, orally, twice daily for 1 week Lansoprazole 30 mg, capsules, orally, twice daily for 1 week Amoxicillin 750 mg, capsules, orally, twice daily for 1 week Clarithromycin 200 or 400 mg, tablets, orally, twice daily for 1 week	Drug: Clarithromycin; Drug: Lansoprazole; Other Names: AG-1749; Drug: Amoxicillin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
H. pylori eradication rate 4 weeks after completion of first-line therapy	The participants are judged to be H. pylori-negative or H. pylori-positive based on the 13C-Urea Breath Test.	4-weeks post-dose (first-line therapy)

Secondary Outcome Measures

Outcome Measure	Time Frame
H. pylori eradication rate 4 weeks after completion of second-line therapy	4-weeks post-dose (second-line therapy)

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut. 2016 Sep;65(9):1439-46. doi: 10.1136/gutjnl-2015-311304. Epub 2016 Mar 2.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: December 30, 2011
• First Submitted That Met QC Criteria: January 3, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Estimate): November 5, 2013
• Last Update Submitted That Met QC Criteria: November 2, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole; Amoxicillin; Clarithromycin
• Other Study ID Numbers: TAK-438/CCT-401; U1111-1126-5073 (Registry Identifier: WHO); JapicCTI-111722 (Registry Identifier: JapicCTI)