Efficacy of TAK-438 Compared to AG-1749 (Lansoprazole) in the Treatment of Erosive Esophagitis

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of TAK-438 (20 mg Once-Daily) Compared to AG-1749 (30mg Once-Daily) in Patients With Erosive Esophagitis

The purpose of this study is to determine the efficacy of TAK-438, once daily (QD), compared to lansoprazole in patients with erosive esophagitis of Grade A to D as defined by the LA classification grading system.

Study Overview

• Status: Completed
• Conditions: Erosive Esophagitis
• Intervention / Treatment: Drug: TAK-438; Drug: Placebo; Drug: Placebo; Drug: Lansoprazole

• Study Type: Interventional
• Enrollment (Actual): 409
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan
  • Chiba
    • Abiko-shi, Chiba, Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
    • Itoshima-shi, Fukuoka, Japan
    • Kurume-shi, Fukuoka, Japan
    • Onga-gun, Fukuoka, Japan
  • Gifu
    • Gifu-shi, Gifu, Japan
  • Gunma
    • Annaka-shi, Gunma, Japan
  • Hiroshima
    • Aki-gun, Hiroshima, Japan
    • Hiroshima-shi, Hiroshima, Japan
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan
  • Hyogo
    • Amagasaki-shi, Hyogo, Japan
    • Kobe-shi, Hyogo, Japan
    • Takarazuka-shi, Hyogo, Japan
  • Kagawa
    • Sakade-shi, Kagawa, Japan
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan
  • Kochi
    • Kochi-shi, Kochi, Japan
    • Susaki-shi, Kochi, Japan
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan
  • Kyoto
    • Kyoto-shi, Kyoto, Japan
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan
  • Oita
    • Oita-shi, Oita, Japan
  • Okayama
    • Okayama-shi, Okayama, Japan
  • Osaka
    • Fuziidera-shi, Osaka, Japan
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan
  • Tochigi
    • Otawara-shi, Tochigi, Japan
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan
    • Chuo-ku, Tokyo, Japan
    • Nakano-ku, Tokyo, Japan
    • Ota-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan
  • Yamagata
    • Yamagata-shi, Yamagata, 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. At Visit 1 (start of the observation period), the participant must have endoscopically confirmed erosive esophagitis of Grade A to D, as defined by the LA classification grading system, and the target number of participants who are clearly Grade C or D is 30% (120 participants) or more of the total participants.
2. Outpatient (including inpatient for examination)

Exclusion Criteria:

1. Participants with an esophagus-related complication (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal stenosis, etc.), a history of radiotherapy or cryotherapy of the esophagus, a caustic or physiochemical trauma (esophageal sclerotherapy, etc.). However, participants with Schatzki's ring (mucosal tissue ring around inferior esophageal sphincter) or Barrett's esophagus are allowed to be included.
2. Participants who have received surgery or treatment affecting gastroesophageal reflux (cardioplasty, dilation of esophageal stenosis [excluding Schatzki's ring], etc.), or who have a history of surgery of stomach or duodenum (excluding removal of benign polyp under endoscopy)
3. Participants who have acute upper gastrointestinal bleeding, gastric or duodenal ulcer (mucosal defect with white coating) within 30 days prior to Visit 1 (start of the observation period). However, participants with gastric or duodenal erosions are allowed to be included.
4. Participants with a previous or current history of Zollinger-Ellison syndrome, or other gastric acid hypersecretion disorders

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 QD	Drug: TAK-438; TAK-438 20 mg, tablets, orally, once daily for up to 8 weeks.; Drug: Placebo; TAK-438 placebo-matching tablets, orally, once daily for up to 8 weeks.; Drug: Placebo; Lansoprazole placebo-matching capsules, orally, once daily for up to 8 weeks. For participants whose EE is not endoscopically healed at Week 8, the participants will receive additional treatment of TAK-438 40 mg, tablets, orally, once daily for up to an additional 8 weeks.; Other Names: AG-1749
Active Comparator: AG-1749 30 mg QD	Drug: Placebo; TAK-438 placebo-matching tablets, orally, once daily for up to 8 weeks.; Drug: Placebo; Lansoprazole placebo-matching capsules, orally, once daily for up to 8 weeks. For participants whose EE is not endoscopically healed at Week 8, the participants will receive additional treatment of TAK-438 40 mg, tablets, orally, once daily for up to an additional 8 weeks.; Other Names: AG-1749; Drug: Lansoprazole; Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. For participants whose EE is not endoscopically healed at Week 8, the participants will receive additional treatment of TAK-438 40 mg, tablets, orally, once daily for up to an additional 8 weeks.; Other Names: AG-1749

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic Healing Rate Over 8 Weeks of Erosive Esophagitis	Endoscopic healing of erosive esophagitis is defined as those participants who have endoscopically confirmed EE of Grade O as defined by the Los Angeles (LA) Classification Grading System. The definitions of each grade are: Grade O (No mucosal break), Grade A (Mucosal break <5 mm), Grade B (Mucosal break ≥5 mm), Grade C (Mucosal break continuous between two or more folds and <75% of the circumference) and Grade D (Mucosal break ≥75% of the circumference).	8 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Endoscopic Healing Rate Over 2 Weeks of Erosive Esophagitis	2 Weeks
Endoscopic Healing Rate Over 4 Weeks of Erosive Esophagitis	4 Weeks

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: September 16, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimate): October 17, 2011

Study Record Updates

• Last Update Posted (Estimate): November 9, 2012
• Last Update Submitted That Met QC Criteria: November 7, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Esophageal Diseases; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: TAK-438/CCT-002; U1111-1123-8356 (Registry Identifier: WHO); JapicCTI-111607 (Registry Identifier: JapicCTI)