Gastroesophageal Reflux Disease
Conditions
Keywords
Non-Erosive Gastroesophageal Reflux Disease(GERD),heartburn
Brief summary
The purpose of this study is to assess the efficacy and safety of daily treatment with Dexlansoprazole modified release (MR) (60 mg or 90 mg once daily \[QD\]) compared to placebo QD in relief of daytime and nighttime heartburn over 4 weeks in subjects with gastroesophageal reflux disease (GERD).
Detailed description
This is a Phase 3, randomized, double-blind, multi-center, placebo-controlled, 3-arm study with a 4 week treatment period. This study will compare the efficacy of daily Dexlansoprazole MR (60 mg and 90 mg) with that of placebo when administered orally as a single daily dose in the morning, before breakfast. The study is designed to evaluate symptom relief in subjects with symptomatic non-erosive GERD. Approximately 450 subjects will be enrolled at approximately 120 U.S. and potentially ex U.S. sites. The study consists of two periods; a Screening Period, which will last a minimum of 7 days and a maximum of 21 days, and a treatment period, which will last 4 weeks. Because the development plan for Dexlansoprazole MR was revised, the results of 2 identical studies, T-GD04-082 (NCT00241745) and T-GD04-083 (this posting, NCT00251758), were combined and analyzed as a single larger study, referred to as study T-GD04-082. A total of 908 subjects were included in the combined analysis; 416 subjects were enrolled into Study T-GD04-082 and 492 subjects were enrolled into Study T-GD04-083.
Interventions
Dexlansoprazole MR 60 mg, capsules, orally, once daily for 4 weeks.
DRUGPlacebo
Dexlansoprazole placebo-matching capsules, orally, once daily for 4 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
* Subjects with Non-Erosive Gastroesophageal Reflux Disease identifying their main symptom as heartburn. * History of episodes of heartburn for 6 months or longer prior to screening. * History of episodes of heartburn for 4 or more days during the 7 days prior to Day -1 as recorded in the electronic diary.
Exclusion criteria
* Use of prescription or non-prescription proton pump inhibitors (PPIs), histamine (H2) receptor antagonists, sucralfate, misoprostol or prokinetics throughout the study * Erosive Esophagitis seen on endoscopy during study screening. * Co-existing diseases affecting the esophagus. * Abnormal laboratory values that suggest significant clinical disease. * Known acquired immunodeficiency syndrome (AIDS) * Females pregnant or lactating. * History of Alcohol abuse. * History of Cancer within 3 years prior to screening. * Chronic (\>12 doses per month) use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors * Use of antacids (except for study supplied Gelusil® ) * Use of drugs with significant anticholinergic effects * Need for continuous anticoagulant (blood thinner) therapy * Endoscopic Barrett's esophagus and/or definite dysplastic changes in the esophagus * History of dilatation of esophageal strictures, other than a 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 * Subjects who, in the opinion of the investigator, are unable to comply with the requirements of the study or are unsuitable for any reason. * Acute upper gastrointestinal (UGI) hemorrhage within 4 weeks of the Screening endoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 4 weeks | 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. |
| Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 4 weeks | 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. |
| Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 4 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects enrolled at 157 sites in the United States (75 in Study T-GD04-082 \[NCT00251745\] and 82 in Study T-GD04-083 \[this posting, NCT00251758\]; date of first dose: 07 December 2005; date of last procedure: 23 May 2006).
Pre-assignment details
Subjects with endoscopically documented normal esophageal mucosa were enrolled in Dexlansoprazole Modified Release (MR) or Placebo once daily (QD) treatment group; subjects were instructed that lifestyle or behavioral modifications designed to treat their symptoms of Gastroesophageal Reflux Disease (GERD) should not be altered throughout the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo QD Placebo capsules, orally, once daily for up to 4 weeks. | 292 |
| Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks. | 312 |
| Dexlansoprazole MR 90 mg QD Dexlansoprazole MR 90 mg, capsules, orally, once daily for up to 4 weeks. | 304 |
| Total | 908 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 9 | 11 |
| Overall Study | Lack of Efficacy | 3 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 | 5 |
| Overall Study | Noncompliant | 0 | 2 | 2 |
| Overall Study | Per Investigator Request | 1 | 0 | 0 |
| Overall Study | Per Subject Request | 0 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Unmet Inclusion/Exclusion Criteria | 0 | 6 | 5 |
| Overall Study | Withdrawal by Subject | 13 | 7 | 3 |
Baseline characteristics
| Characteristic | Placebo QD | Dexlansoprazole MR 60 mg QD | Dexlansoprazole MR 90 mg QD | Total |
|---|---|---|---|---|
| Age Continuous | 49.0 years STANDARD_DEVIATION 13.6 | 48.0 years STANDARD_DEVIATION 13.55 | 46.7 years STANDARD_DEVIATION 13.64 | 47.9 years STANDARD_DEVIATION 13.61 |
| Age, Customized 45 - <65 years | 146 participants | 155 participants | 139 participants | 440 participants |
| Age, Customized <45 years | 107 participants | 125 participants | 135 participants | 367 participants |
| Age, Customized ≥65 years | 39 participants | 32 participants | 30 participants | 101 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 60 Participants | 58 Participants | 61 Participants | 179 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 232 Participants | 254 Participants | 243 Participants | 729 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 3 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 12 Participants | 7 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 46 Participants | 41 Participants | 121 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 1 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 240 Participants | 246 Participants | 245 Participants | 731 Participants |
| Sex: Female, Male Female | 216 Participants | 214 Participants | 213 Participants | 643 Participants |
| Sex: Female, Male Male | 76 Participants | 98 Participants | 91 Participants | 265 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 | 37 / — | 55 / — | 54 / — |
| serious Total, serious adverse events | 0 / — | 2 / — | 1 / — |
Outcome results
Primary
Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic 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.
Time frame: 4 weeks
Population: Analysis was conducted on an intent-to-treat (ITT) population that included all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment. All ITT populations excluded subjects with confirmed Barrett's esophagus and/or definite dysplastic changes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 24.9 percentage of days | Standard Deviation 25.7 |
| Dexlansoprazole MR 60 mg QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 44.8 percentage of days | Standard Deviation 33.8 |
| Dexlansoprazole MR 90 mg QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 49.1 percentage of days | Standard Deviation 34.2 |
Primary
Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic 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 marked.
Time frame: 4 weeks
Population: Analysis was conducted on an intent-to-treat (ITT) population that included all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment. All ITT populations excluded subjects with confirmed Barrett's esophagus and/or definite dysplastic changes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 17.0 percentage of days |
| Dexlansoprazole MR 60 mg QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 45.7 percentage of days |
| Dexlansoprazole MR 90 mg QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 52.7 percentage of days |
Comparison: The comparison between the two treatment groups was made using Wilcoxon rank-sum test.p-value: <0.00001Wilcoxon (Mann-Whitney)
Comparison: The comparison between the two treatment groups was made using Wilcoxon rank-sum test.p-value: <0.00001Wilcoxon (Mann-Whitney)
Comparison: The comparison between the two treatment groups was made using Wilcoxon rank-sum test.p-value: 0.15505Wilcoxon (Mann-Whitney)
Secondary
Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic 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.
Time frame: 4 weeks
Population: Analysis was conducted on an ITT population (all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment), but excluded subjects without any morning diary entries on Day 1 or later.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 49.6 percentage of days | Standard Deviation 34.1 |
| Dexlansoprazole MR 60 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 62.0 percentage of days | Standard Deviation 34.5 |
| Dexlansoprazole MR 90 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 64.4 percentage of days | Standard Deviation 34.6 |
Secondary
Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic 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.
Time frame: 4 weeks
Population: Analysis was conducted on an ITT population (all randomized subjects who received at least 1 dose of study drug and completed at least 1 diary entry for heartburn during treatment), but excluded subjects without any morning diary entries on Day 1 or later.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 51.0 percentage of days |
| Dexlansoprazole MR 60 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 72.3 percentage of days |
| Dexlansoprazole MR 90 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 76.6 percentage of days |
Comparison: The comparison between the two treatment groups was made using Wilcoxon rank-sum test.p-value: 0.00001Wilcoxon (Mann-Whitney)
Comparison: The comparison between the two treatment groups was made using Wilcoxon rank-sum test.p-value: <0.00001Wilcoxon (Mann-Whitney)
Comparison: The comparison between the two treatment groups was made using Wilcoxon rank-sum test.p-value: 0.3874Wilcoxon (Mann-Whitney)