Efficacy and Safety of Dexlansoprazole MR Compared to Placebo on Maintaining Healing in Subjects With Healed Erosive Esophagitis

A Phase 3 Study to Evaluate the Safety and Efficacy of TAK-390MR (30 mg QD and 60 mg QD) Compared to Placebo in Maintenance of Healing in Subjects With Healed Erosive Esophagitis.

The purpose of this study is to assess the ability of once-daily (QD) treatment with dexlansoprazole modified release (MR) 30 mg and 60 mg or placebo in maintaining healing of erosive esophagitis (EE).

Study Overview

• Status: Completed
• Conditions: Esophagitis, Peptic; Esophagitis, Reflux
• Intervention / Treatment: Drug: Placebo; Drug: Dexlansoprazole MR; Drug: Dexlansoprazole MR

Detailed Description

This is a Phase 3, randomized, double-blind, multicenter, placebo-controlled, 6 month maintenance study. The study is designed to compare the efficacy and safety of daily dexlansoprazole MR (30 mg and 60 mg) with that of placebo, in maintaining healing of EE.

• Study Type: Interventional
• Enrollment (Actual): 445
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Kippa Ring, Australia
• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada
  • Ontario
    • Newmarket, Ontario, Canada
    • Richmond Hill, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Longueuil, Quebec, Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada
• Czech Republic
  • Hradec Kralove, Czech Republic
• Estonia
  • Tallinn, Estonia
• Latvia
  • Riga, Latvia
  • Valmiera, Latvia
• Lithuania
  • Kaunas, Lithuania
  • Panevezys, Lithuania
  • Vilnius, Lithuania
• Slovakia
  • Bratislava, Slovakia
  • Nitra, Slovakia
  • Presov, Slovakia
  • Sucany, Slovakia
• United States
  • Alabama
    • Huntsville, Alabama, United States
  • Arizona
    • Tuscon, Arizona, United States
  • California
    • Anaheim, California, United States
    • Azusa, California, United States
    • Carmichael, California, United States
    • Chula Vista, California, United States
    • Cypress, California, United States
    • Fresno, California, United States
    • Garden Grove, California, United States
    • Harrisburg, California, United States
    • Irvine, California, United States
    • Lancaster, California, United States
    • Mission Hills, California, United States
    • Oakland, California, United States
    • Orange, California, United States
    • Pasadena, California, United States
    • San Diego, California, United States
    • San Luis Obispo, California, United States
  • Colorado
    • Boulder, Colorado, United States
    • Colorado Springs, Colorado, United States
    • Wheat Ridge, Colorado, United States
  • Florida
    • Boynton Beach, Florida, United States
    • Jupiter, Florida, United States
    • Miami, Florida, United States
    • New Smyma Beach, Florida, United States
    • Ocala, Florida, United States
    • St. Petersburg, Florida, United States
    • Zephyrhills, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Idaho
    • Boise, Idaho, United States
  • Illinois
    • Moline, Illinois, United States
    • Oak Forrest, Illinois, United States
    • Rockford, Illinois, United States
  • Iowa
    • Clive, Iowa, United States
  • Kentucky
    • Lexington, Kentucky, United States
  • Louisiana
    • Baton Rouge, Louisiana, United States
    • Metairie, Louisiana, United States
  • Maryland
    • Chevy Chase, Maryland, United States
    • Hollywood, Maryland, United States
    • Lutherville, Maryland, United States
    • Prince Federick, Maryland, United States
  • Minnesota
    • Chaska, Minnesota, United States
  • Mississippi
    • Jackson, Mississippi, United States
  • Missouri
    • Jefferson City, Missouri, United States
    • Washington, Missouri, United States
  • New Jersey
    • Egg Harbor Township, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • Binghamton, New York, United States
    • Rochester, New York, United States
  • North Carolina
    • Greensboro, North Carolina, United States
    • High Point, North Carolina, United States
    • Raleigh, North Carolina, United States
  • North Dakota
    • Bismark, North Dakota, United States
  • Ohio
    • Dayton, Ohio, United States
    • Mogadore, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Oregon
    • Medford, Oregon, United States
    • Portland, Oregon, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
    • Lansdale, Pennsylvania, United States
  • South Carolina
    • Anderson, South Carolina, United States
    • Mount Pleasant, South Carolina, United States
  • Tennessee
    • Bristol, Tennessee, United States
    • Chattanooga, Tennessee, United States
    • Germantown, Tennessee, United States
    • Jackson, Tennessee, United States
    • Kingsport, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Amarillo, Texas, United States
    • Fort Worth, Texas, United States
    • Houston, Texas, United States
    • San Antonio, Texas, United States
  • Utah
    • Ogden, Utah, United States
  • Virginia
    • Charlottesville, Virginia, United States
    • Chesapeake, Virginia, United States
  • Washington
    • Spokane, Washington, United States
    • Tacoma, Washington, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States
    • Monroe, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have successfully completed the Phase 3 Study T-EE04-084 (NCT00251693) or T-EE04-085 (NCT00251719); and have healed esophageal erosions proven by endoscopy. Complete healing was assessed for change in LA Esophagitis Classification grades A, B, C, or D to healed (defined as anything less than the criterion for Grade A). The subject was counted as healed if endoscopy findings did not meet the Grade A criterion.

Exclusion Criteria:

• Use of prescription or nonprescription proton pump inhibitors (PPIs), histamine (H2) receptor antagonists, sucralfate, misoprostol, or prokinetics throughout the study.
• Use of antacids (except for study supplied) throughout the study.
• Use of drugs with significant anticholinergic effects such as tricyclics who cannot stay on a stable dose throughout the study.
• Chronic (>12 doses per month) use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors.
• Need for continuous anticoagulant therapy.
• Evidence of uncontrolled systemic disease.
• Subjects who have participated in either maintenance study (T-EE04-086 [NCT00255164] or T-EE04-087 [NCT00255151]).
• Subjects who, in the opinion of the investigator, is unable to comply with the requirements of the study or is unsuitable for any reason.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Dexlansoprazole placebo-matching capsules, orally, once daily for up to six months.
Experimental: Dexlansoprazole MR 60 mg QD	Drug: Dexlansoprazole MR; Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to six months.; Other Names: TAK-390MR; Kapidex; Dexilant; Drug: Dexlansoprazole MR; Dexlansoprazole MR 60 mg, orally, once daily for up to six months.; Other Names: TAK-390MR; Kapidex; Dexilant
Experimental: Dexlansoprazole MR 30 mg QD	Drug: Dexlansoprazole MR; Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to six months.; Other Names: TAK-390MR; Kapidex; Dexilant; Drug: Dexlansoprazole MR; Dexlansoprazole MR 60 mg, orally, once daily for up to six months.; Other Names: TAK-390MR; Kapidex; Dexilant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Maintained Complete Healing of Erosive Esophagitis as Assessed by Endoscopy - Crude Rate Analysis.	Crude rates analyzed maintenance of healed EE from baseline of this study and considered prematurely discontinued subjects as relapsed.	6 months
Percentage of Subjects Who Maintained Complete Healing of Erosive Esophagitis as Assessed by Endoscopy - Life Table Method	Percentage of subjects who maintained complete healing of erosive esophagitis as assessed by endoscopy. In the life table method, subjects without post-baseline endoscopy were included as censored; subjects who did not have a recurrence of EE and did not complete the study were also considered censored.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days Without Daytime or Nighttime Heartburn as Assessed by Daily Diary-Median.	The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was reported.	6 months
Percentage of Days Without Nighttime Heartburn as Assessed by Daily Diary-Median.	The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.	6 months
Percentage of Days Without Nighttime Heartburn as Assessed by Daily Diary-Mean.	The percentage was calculated as the nights that were heartburn-free out of the total number of days for which a nighttime result was marked.	6 months
Percentage of Days Without Daytime or Nighttime Heartburn as Assessed by Daily Diary-Mean.	The percentage was calculated as the days that were heartburn-free out of the total number of days for which either a daytime or nighttime result was marked.	6 months

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Peura DA, Metz DC, Dabholkar AH, Paris MM, Yu P, Atkinson SN. Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1010-21. doi: 10.1111/j.1365-2036.2009.04137.x. Epub 2009 Sep 4.
• Wyrwich KW, Mody R, Larsen LM, Lee M, Harnam N, Revicki DA. Validation of the PAGI-SYM and PAGI-QOL among healing and maintenance of erosive esophagitis clinical trial participants. Qual Life Res. 2010 May;19(4):551-64. doi: 10.1007/s11136-010-9620-x. Epub 2010 Feb 27.
• Friedlander EA, Pallentino J, Miller SK, VanBeuge SS. The evolution of proton pump inhibitors for the treatment of gastroesophageal reflux disease. J Am Acad Nurse Pract. 2010 Dec;22(12):674-83. doi: 10.1111/j.1745-7599.2010.00578.x. Epub 2010 Nov 24.
• Metz DC, Howden CW, Perez MC, Larsen L, O'Neil J, Atkinson SN. Clinical trial: dexlansoprazole MR, a proton pump inhibitor with dual delayed-release technology, effectively controls symptoms and prevents relapse in patients with healed erosive oesophagitis. Aliment Pharmacol Ther. 2009 Apr 1;29(7):742-54. doi: 10.1111/j.1365-2036.2009.03954.x. Epub 2009 Feb 7.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: May 2, 2006
• First Submitted That Met QC Criteria: May 2, 2006
• First Posted (Estimate): May 4, 2006

Study Record Updates

• Last Update Posted (Estimate): February 3, 2012
• Last Update Submitted That Met QC Criteria: February 1, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Erosive Esophagitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Diseases; Peptic Ulcer; Duodenal Diseases; Esophagitis, Peptic; Esophagitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: T-EE05-135; 2006-000419-90 (EudraCT Number); U1111-1113-9433 (Registry Identifier: WHO)