Efficacy and Safety of Dexlansoprazole MR and Lansoprazole on Healing of Erosive Esophagitis

• Percentage of Subjects With Complete Healing of Erosive Esophagitis (EE) by Week 8 as Assessed by Endoscopy - Crude Rate Analysis. [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A (greater than or equal to 1 mucosal break and less than 5 mm). If it doesn't meet the A criterion, it's counted as healed.
• Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

• Percentage of Subjects With Baseline Erosive Esophagitis Grade C or D Combined Who Have Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis. [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Percentage of subjects with baseline EE grade C or D combined who have complete healing of erosive esophagitis as assessed by endoscopy for Change in LA Esophagitis Classification Grades C and D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.
• Percentage of Subjects With Baseline Erosive Esophagitis Grade C or D Combined Who Have Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method. [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
  Percentage of subjects with baseline EE grade C or D combined who have complete healing of EE as assessed by endoscopy for Change in LA Esophagitis Classification Grades C and D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.
• Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Crude Rate Analyses. [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
  Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.
• Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Life Table Method. [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
  Percentage of subjects with complete healing of EE as assessed by endoscopy was analyzed for change in LA Esophagitis Classification grades A, B, C, or D to healed. Healed is defined as anything that is less than the criterion for Grade A. If it doesn't meet the A criterion, it's counted as healed.

• - Percentage of subjects with complete healing of erosive esophagitis over 4 weeks as assessed by endoscopy.
• - Percentage of subjects with baseline esophagitis grade C or D combined who have complete healing of erosive esophagitis over 8 weeks as assessed by endoscopy.

The purpose of this study is to assess the efficacy and safety of 8 weeks of once-daily (QD) treatment with dexlansoprazole modified release (MR) 60 mg or 90 mg or lansoprazole 30 mg in healing subjects with endoscopically proven erosive esophagitis.

This is a Phase 3, randomized, double-blind, multi-center, active-controlled, 3-arm study with an 8-week treatment period. This study will compare the efficacy of dexlansoprazole MR (60 mg QD and 90 mg QD) with that of lansoprazole (30 mg) when administered orally as a single daily dose in the morning, before breakfast. The study is designed to evaluate healing of erosive esophagitis and the effect of the therapy on relieving gastroesophageal reflux disease-related symptoms. The study consists of two periods, a screening period (maximum 21 days) and a treatment period, which will last 8 weeks.

• Esophagitis, Reflux
• Esophagitis, Peptic

• Drug: Dexlansoprazole MR
  Dexlansoprazole MR 60 mg, capsules, orally, once daily (QD) for up to 8 weeks.
  Other Names:

  • TAK-390MR
  • Kapidex
  • Dexilant
• Drug: Dexlansoprazole MR
  Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks.
  Other Names:

  • TAK-390MR
  • Kapidex
  • Dexilant
• Drug: Lansoprazole
  Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
  Other Names:

  • Prevacid
  • AG-1749

• Experimental: Dexlansoprazole MR 60 mg QD
  Intervention: Drug: Dexlansoprazole MR
• Experimental: Dexlansoprazole MR 90 mg QD
  Intervention: Drug: Dexlansoprazole MR
• Active Comparator: Lansoprazole 30 mg QD
  Intervention: Drug: Lansoprazole

• Sharma P, Shaheen NJ, Perez MC, Pilmer BL, Lee M, Atkinson SN, Peura D. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation--results from two randomized controlled studies. Aliment Pharmacol Ther. 2009 Apr 1;29(7):731-41.
• 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. 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. 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. Epub 2010 Nov 24.
• Peura DA, Pilmer B, Hunt B, Mody R, Perez MC. The effects of increasing body mass index on heartburn severity, frequency and response to treatment with dexlansoprazole or lansoprazole. Aliment Pharmacol Ther. 2013 Apr;37(8):810-8. doi: 10.1111/apt.12270. Epub 2013 Mar 4.

Inclusion Criteria:

• Subject must have endoscopically confirmed erosive esophagitis as defined by the Los Angeles (LA) Classification Grading System (A-D)

Exclusion Criteria:

• Subject has a positive Campylobacter-like organisms (CLO) test for Helicobacter (H.) pylori.
• Use of prescription or non-prescription proton pump inhibitors (PPIs), histamine (H2) receptor antagonists or sucralfate, drugs with significant anticholinergic effects, misoprostol or prokinetics
• Use of antacids [except for study supplied Gelusil®]
• Need for continuous anticoagulant therapy (blood thinners)
• Endoscopic Barrett's esophagus and/or definite dysplastic changes in the esophagus
• History of dilatation of esophageal strictures, other than Schatzki's ring (a ring of mucosal tissue near the lower esophageal sphincter)
• Current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition.
• History of gastric, duodenal or esophageal surgery except simple oversew of an ulcer.
• Acute upper gastrointestinal hemorrhage within 4 weeks of the screening endoscopy