Esophagitis, Peptic, Esophagitis, Reflux
Conditions
Keywords
Erosive Esophagitis
Brief summary
This is a study to assess the efficacy and safety of 8 weeks of treatment with Dexlansoprazole modified release (MR)(60 mg daily and 90 mg daily) compared to Lansoprazole (30 mg daily) in healing subjects with endoscopically proven erosive esophagitis.
Detailed description
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 and 90 mg) 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 up to 8 weeks.
Interventions
Dexlansoprazole MR 60 mg, capsules, orally, once daily (QD) for up to 8 weeks.
DRUGLansoprazole
Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (UGI) hemorrhage within 4 weeks of the Screening endoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis. | 8 Weeks | Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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 | 8 Weeks | Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Week 8 | Percentage of subjects with baseline EE grade C or D combined who have complete healing of EE as assessed by endoscopy. Change in LA Classification grades C or D to healed was measured. 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. | 8 Weeks | Percentage of subjects with baseline EE grade C or D combined who have complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades C or D to healed was measured. 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 Analysis. | 4 Weeks | Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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 | 4 Weeks | Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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. |
Countries
Australia, Bulgaria, Canada, Colombia, Czechia, Germany, India, Latvia, Lithuania, New Zealand, Peru, Poland, Russia, Slovakia, South Africa, United States
Participant flow
Recruitment details
Subjects were enrolled at 93 sites in the US and 63 ex-US sites from 16 December 2005 to 22 January 2007.
Pre-assignment details
Subjects recorded day and nighttime heartburn symptoms and rescue medications for a screening period of up to 21 days. Subjects with endoscopically-proven erosive esophagitis (EE) at screening were enrolled in Dexlansoprazole Modified Release (MR) or Lansoprazole once daily (QD) treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 8 weeks. | 694 |
| Dexlansoprazole MR 90 mg QD Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 8 weeks. | 687 |
| Lansoprazole 30 mg QD Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. | 673 |
| Total | 2,054 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 14 | 8 | 7 |
| Overall Study | Barrett's esophagus | 2 | 2 | 0 |
| Overall Study | Inclusion/exclusion criteria not met | 12 | 6 | 2 |
| Overall Study | Investigator decision | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 11 | 8 |
| Overall Study | Noncompliance | 2 | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 12 | 11 |
Baseline characteristics
| Characteristic | Total | Lansoprazole 30 mg QD | Dexlansoprazole MR 90 mg QD | Dexlansoprazole MR 60 mg QD |
|---|---|---|---|---|
| Age Continuous | 47.9 years STANDARD_DEVIATION 13.66 | 47.3 years STANDARD_DEVIATION 13.65 | 47.7 years STANDARD_DEVIATION 13.8 | 48.7 years STANDARD_DEVIATION 13.53 |
| Age, Customized < 45 Years | 842 participants | 294 participants | 293 participants | 255 participants |
| Age, Customized 45 Years to < 65 Years | 972 participants | 314 participants | 310 participants | 348 participants |
| Age, Customized >= 65 Years | 240 participants | 65 participants | 84 participants | 91 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 192 Participants | 58 Participants | 67 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1862 Participants | 615 Participants | 620 Participants | 627 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| LA Classification Grade A: ≥1 mucosal break <5 mm | 727 participant | 222 participant | 271 participant | 234 participant |
| LA Classification Grade B: ≥1 mucosal break ≥5 mm | 735 participant | 257 participant | 221 participant | 257 participant |
| LA Classification Grade C: ≥1 mucosal break and <75% of the circumference | 458 participant | 150 participant | 152 participant | 156 participant |
| LA Classification Grade D: ≥1 mucosal break and ≥75% of the circumference | 132 participant | 44 participant | 42 participant | 46 participant |
| LA Classification Grade NA | 2 participant | 0 participant | 1 participant | 1 participant |
| Race (NIH/OMB) American Indian or Alaska Native | 25 Participants | 7 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 90 Participants | 25 Participants | 32 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 96 Participants | 32 Participants | 30 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 68 Participants | 24 Participants | 23 Participants | 21 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 1770 Participants | 584 Participants | 588 Participants | 598 Participants |
| Sex: Female, Male Female | 963 Participants | 311 Participants | 335 Participants | 317 Participants |
| Sex: Female, Male Male | 1091 Participants | 362 Participants | 352 Participants | 377 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 694 | 31 / 687 | 23 / 673 |
| serious Total, serious adverse events | 4 / 694 | 4 / 687 | 2 / 673 |
Outcome results
Primary
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis.
Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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.
Time frame: 8 Weeks
Population: Crude rate analysis were performed on the ITT subjects who had at least 1 post-baseline endoscopy assessment that was performed within 7 days of the last day of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexlansoprazole MR 60 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis. | 86.9 percentage of subjects |
| Dexlansoprazole MR 90 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis. | 89.4 percentage of subjects |
| Lansoprazole 30 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Crude Rate Analysis. | 84.6 percentage of subjects |
p-value: 0.23495% CI: [-1.45, 6.14]Cochran-Mantel-Haenszel
p-value: 0.01995% CI: [1.2, 8.5]Cochran-Mantel-Haenszel
p-value: 0.22Cochran-Mantel-Haenszel
Primary
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method
Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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.
Time frame: 8 Weeks
Population: In addition to the ITT subjects who had at least 1 post-baseline endoscopy, Life Table Method included the ITT subjects without any post-baseline endoscopy within 7 days of the last day of study drug as censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexlansoprazole MR 60 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method | 93.1 percentage of subjects |
| Dexlansoprazole MR 90 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method | 94.9 percentage of subjects |
| Lansoprazole 30 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 8 as Assessed by Endoscopy - Life Table Method | 91.5 percentage of subjects |
p-value: 0.16795% CI: [-1.65, 4.96]Log Rank
p-value: 0.0395% CI: [0.27, 6.5]Log Rank
p-value: 0.413Log Rank
Secondary
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.
Percentage of subjects with baseline EE grade C or D combined who have complete healing of EE as assessed by endoscopy. Change in LA Classification grades C or D to healed was measured. 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.
Time frame: Week 8
Population: Crude rate analyses were performed on the ITT subjects who had at least 1 post-baseline endoscopy assessment performed within 7 days of the last day of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexlansoprazole MR 60 mg QD | 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. | 77.8 percentage of subjects |
| Dexlansoprazole MR 90 mg QD | 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. | 86.3 percentage of subjects |
| Lansoprazole 30 mg QD | 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. | 78.9 percentage of subjects |
p-value: 0.768Cochran-Mantel-Haenszel
p-value: 0.064Cochran-Mantel-Haenszel
p-value: 0.034Cochran-Mantel-Haenszel
Secondary
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.
Percentage of subjects with baseline EE grade C or D combined who have complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades C or D to healed was measured. 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.
Time frame: 8 Weeks
Population: In addition to the ITT subjects who had at least 1 post-baseline endoscopy, Life Table Method included the ITT subjects without any post-baseline endoscopy within 7 days of the last day of study drug as censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexlansoprazole MR 60 mg QD | 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. | 87.6 percentage of subjects |
| Dexlansoprazole MR 90 mg QD | 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. | 93.3 percentage of subjects |
| Lansoprazole 30 mg QD | 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. | 87.7 percentage of subjects |
p-value: 0.727Log Rank
p-value: 0.064Log Rank
p-value: 0.174Log Rank
Secondary
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Crude Rate Analysis.
Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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.
Time frame: 4 Weeks
Population: Crude rate analyses were performed on the ITT subjects who had at least 1 post-baseline endoscopy assessment performed within 7 days of the last day of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexlansoprazole MR 60 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Crude Rate Analysis. | 69.7 percentage of subjects |
| Dexlansoprazole MR 90 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Crude Rate Analysis. | 70.6 percentage of subjects |
| Lansoprazole 30 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Crude Rate Analysis. | 65.4 percentage of subjects |
p-value: 0.1Cochran-Mantel-Haenszel
p-value: 0.125Cochran-Mantel-Haenszel
p-value: 0.993Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Life Table Method
Percentage of subjects with complete healing of EE as assessed by endoscopy. Change in LA Esophagitis Classification grades A, B, C, D to healed was measured. 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.
Time frame: 4 Weeks
Population: In addition to the ITT subjects who had at least 1 post-baseline endoscopy, Life Table Method included the ITT subjects without any post-baseline endoscopy within 7 days of the last day of study drug as censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexlansoprazole MR 60 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Life Table Method | 80.1 percentage of subjects |
| Dexlansoprazole MR 90 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Life Table Method | 80.4 percentage of subjects |
| Lansoprazole 30 mg QD | Percentage of Subjects With Complete Healing of Erosive Esophagitis by Week 4 as Assessed by Endoscopy - Life Table Method | 77.0 percentage of subjects |
p-value: 0.117Log Rank
p-value: 0.124Log Rank
p-value: 0.949Log Rank