Long-term Extension Study of TAK-438 for the Prevention of Recurrent Gastric or Duodenal Ulcers During Therapy of Non-steroidal Anti-inflammatory Drug (NSAID)

A Phase 3, Multicenter, Single-blind, AG-1749-controlled, Parallel-group, Long-term Extension Study to Evaluate the Safety and Efficacy of TAK-438 (10 mg or 20 mg, Orally, Once Daily) for the Prevention of Recurrent Gastric or Duodenal Ulcers During Long-term Therapy of Non-steroidal Anti-inflammatory Drug (NSAID)

The purpose of this study is to evaluate the safety of TAK-438, once daily (QD), during long-term concomitant non-steroidal anti-inflammatory drug (NSAID) therapy in patients with a history of gastric or duodenal ulcer who require long-term therapy of NSAID.

Study Overview

• Status: Completed
• Conditions: Gastric Ulcers; Duodenal Ulcers
• Intervention / Treatment: Drug: TAK-438; Drug: Placebo; Drug: TAK-438; Drug: Placebo; Drug: Placebo; Drug: Lansoprazole

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Kasugai-shi, Aichi, Japan
    • Nagoya-shi, Aichi, Japan
    • Seto-shi, Aichi, Japan
  • Akita
    • Akita-shi, Akita, Japan
  • Chiba
    • Funabashi-shi, Chiba, Japan
    • Ichihara-shi, Chiba, Japan
    • Nagareyama-shi, Chiba, Japan
  • Ehime
    • Matsuyama-shi, Ehime, Japan
    • Niihama-shi, Ehime, Japan
    • Saijo-shi, Ehime, Japan
  • Fukui
    • Fukui-shi, Fukui, Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan
    • Itoshima-shi, Fukuoka, Japan
    • Kitakyusyu-shi, Fukuoka, Japan
    • Munakata-shi, Fukuoka, Japan
    • Onga-gun, Fukuoka, Japan
    • Tagawa-shi, Fukuoka, Japan
    • Yukuhashi-shi, Fukuoka, Japan
  • Fukushima
    • Fukushima-shi, Fukushima, Japan
    • Koriyama-shi, Fukushima, Japan
  • Gunma
    • Mebashi-shi, Gunma, Japan
    • Takasaki-shi, Gunma, Japan
  • Hiroshima
    • Fukuyama-shi, Hiroshima, Japan
    • Hatsukaichi-shi, Hiroshima, Japan
    • Higashihirosima-shi, Hiroshima, Japan
  • Hokkaido
    • Asahikawa-shi, Hokkaido, Japan
    • Hakodate-shi, Hokkaido, Japan
    • Obihiro-shi, Hokkaido, Japan
    • Sapporo-shi, Hokkaido, Japan
    • Sunagawa-shi, Hokkaido, Japan
    • Tomakomai-shi, Hokkaido, Japan
  • Hyogo
    • Akashi-shi, Hyogo, Japan
    • Himeji-shi, Hyogo, Japan
    • Itami-shi, Hyogo, Japan
    • Kako-gun, Hyogo, Japan
    • Kato-shi, Hyogo, Japan
    • Kobe-shi, Hyogo, Japan
    • Nishinomiya-shi, Hyogo, Japan
  • Ibaragi
    • Higashiibaragi-gun, Ibaragi, Japan
    • Koga-shi, Ibaragi, Japan
    • Mito-shi, Ibaragi, Japan
  • Ishikawa
    • Hakusan-shi, Ishikawa, Japan
    • Komatsu-shi, Ishikawa, Japan
  • Kagawa
    • Takamatsu-shi, Kagawa, Japan
  • Kanagawa
    • Kamakura-shi, Kanagawa, Japan
    • Kawasaki-shi, Kanagawa, Japan
    • Sagamihara-shi, Kanagawa, Japan
    • Yokohama-shi, Kanagawa, Japan
  • Kochi
    • Kochi-shi, Kochi, Japan
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan
  • Kyoto
    • Uji-shi, Kyoto, Japan
  • Mie
    • Tsu-shi, Mie, Japan
  • Miyagi
    • Sendai-shi, Miyagi, Japan
  • Nagano
    • Matsumoto-shi, Nagano, Japan
    • Nagano-shi, Nagano, Japan
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan
  • Nara
    • Ikoma-shi, Nara, Japan
    • Nara-shi, Nara, Japan
  • Nigata
    • Nigata-shi, Nigata, Japan
  • Oita
    • Beppu-shi, Oita, Japan
    • Oita-shi, Oita, Japan
    • Yuhu-shi, Oita, Japan
  • Okayama
    • Kurashiki-shi, Okayama, Japan
  • Osaka
    • Higashiosaka-shi, Osaka, Japan
    • Moriguchi-shi, Osaka, Japan
    • Osaka-shi, Osaka, Japan
    • Osakasayama-shi, Osaka, Japan
    • Tondabayashi-shi, Osaka, Japan
  • Saga
    • Ogi-shi, Saga, Japan
  • Saitama
    • Ageo-shi, Saitama, Japan
    • Hiki-gun, Saitama, Japan
    • Kasukabe-shi, Saitama, Japan
    • Kumagaya-shi, Saitama, Japan
    • Saitama-shi, Saitama, Japan
    • Sayama-shi, Saitama, Japan
    • Toda-shi, Saitama, Japan
    • Tokorozawa-shi, Saitama, Japan
  • Shiga
    • Otsu-shi, Shiga, Japan
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan
    • Shizuoka-shi, Shizuoka, Japan
  • Tokushima
    • Naruto-shi, Tokushima, Japan
  • Tokyo
    • Adachi-ku, Tokyo, Japan
    • Bunkyo-ku, Tokyo, Japan
    • Hachiouji-shi, Tokyo, Japan
    • Koto-ku, Tokyo, Japan
    • Meguro-ku, Tokyo, Japan
    • Minato-ku, Tokyo, Japan
    • Musashimurayama-shi, Tokyo, Japan
    • Nakano-ku, Tokyo, Japan
    • Ota-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan
    • Sumida-ku, Tokyo, Japan
  • Tottori
    • Yonago-shi, Tottori, Japan
  • Toyama
    • Tonami-shi, Toyama, Japan
    • Toyama-shi, Toyama, Japan
  • Yamaguchi
    • Shimonoseki-shi, Yamaguchi, Japan
    • Ube-shi, Yamaguchi, 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 who require continuous NSAID therapy during the treatment period with the study drug
2. Participants who have completed the preceding study
3. Outpatient (including inpatient for examinations)

Exclusion Criteria:

1. Participants deemed to be ineligible to participate in the study by the principal investigator or investigator due to the occurrence of adverse events in the preceding study
2. Participants who are scheduled to change the type and dosage regimen of NSAID
3. Participants with ulcers or bleeding in stomach or duodenum, endoscopically confirmed during the preceding study
4. Participants with small intestine bleeding, large intestine bleeding, or gastrointestinal bleeding of unknown etiology
5. Participants who have a history of surgery which affects gastric acid secretion (e.g., resection of upper gastrointestinal tract, vagotomy) or who are scheduled to undergo such surgery
6. Participants with a previous or current history of Zollinger-Ellison syndrome, or other gastric acid hypersecretion disorders
7. Participants with a previous or current history of aspirin-induced asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-438 10 mg QD	Drug: TAK-438; TAK-438 10 mg tablets, orally, once daily for 28-80 weeks.; Drug: Placebo; Lansoprazole placebo matching capsules, orally, once daily for 28-80 weeks.; Drug: TAK-438; TAK-438 20 mg tablets, orally, once daily for 28-80 weeks.; Drug: Placebo; Lansoprazole placebo-matching capsules, orally, once daily for 28-80 weeks.; Drug: Placebo; TAK-438 placebo-matching tablets, orally, once daily for 28-80 weeks.
Experimental: TAK-438 20 mg QD	Drug: TAK-438; TAK-438 10 mg tablets, orally, once daily for 28-80 weeks.; Drug: Placebo; Lansoprazole placebo matching capsules, orally, once daily for 28-80 weeks.; Drug: TAK-438; TAK-438 20 mg tablets, orally, once daily for 28-80 weeks.; Drug: Placebo; Lansoprazole placebo-matching capsules, orally, once daily for 28-80 weeks.; Drug: Placebo; TAK-438 placebo-matching tablets, orally, once daily for 28-80 weeks.
Active Comparator: Lansoprazole 15 mg QD	Drug: Placebo; Lansoprazole placebo matching capsules, orally, once daily for 28-80 weeks.; Drug: Placebo; Lansoprazole placebo-matching capsules, orally, once daily for 28-80 weeks.; Drug: Placebo; TAK-438 placebo-matching tablets, orally, once daily for 28-80 weeks.; Drug: Lansoprazole; Lansoprazole 15 mg capsules, orally, once daily for 28-80 weeks.; Other Names: AG-1749

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through the last visit of study.	Up to 80 weeks.

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Laboratory values	Up to 80 weeks.
Change from baseline in Electrocardiograms	Up to 80 weeks.
Change from baseline in Vital signs	Up to 80 weeks.
Change from baseline in Serum gastrin	Up to 80 weeks.
Change from baseline in Pepsinogen I and II	Up to 80 weeks.
Recurrence rate of gastric or duodenal ulcer	Up to 80 weeks.

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Mizokami Y, Oda K, Funao N, Nishimura A, Soen S, Kawai T, Ashida K, Sugano K. Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study. Gut. 2018 Jun;67(6):1042-1051. doi: 10.1136/gutjnl-2017-314010. Epub 2017 Oct 7.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: September 16, 2011
• First Submitted That Met QC Criteria: October 18, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Estimate): May 8, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Ulcer; Stomach Ulcer; Duodenal Ulcer; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: TAK-438/OCT-301; U1111-1123-8762 (Registry Identifier: WHO); JapicCTI-111611 (Registry Identifier: JapicCTI)