Gastroesophageal Reflux Disease
Conditions
Keywords
Gastroesophageal Reflux Disease(GERD), Heartburn
Brief summary
The purpose of this study is to assess the efficacy and safety of Dexlansoprazole modified release (MR) (30 mg once daily \[QD\] or 60 mg QD) compared to placebo in relief of daytime and nighttime heartburn over 4 weeks in subjects with symptomatic, nonerosive gastroesophageal reflux disease (GERD).
Detailed description
This is a Phase 3, randomized, double-blind, multicenter, placebo-controlled, 3-arm study with a 4 week treatment period. This study will compare the efficacy of Dexlansoprazole MR (30 mg QD and 60 mg QD) 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 nonerosive GERD. Approximately 900 subjects will be enrolled at approximately 200 United States (US) and potentially ex-US 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.
Interventions
Dexlansoprazole MR 30 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 identifying their main symptom as a burning feeling in the mid epigastric area and/or chest area (ie, heartburn). * Subject has a history of episodes of heartburn for 6 months or longer prior to Screening. * Subject must have a history of episodes of heartburn for 4 or more days during the 7 days prior to Day -1.
Exclusion criteria
* Endoscopic Barrett's esophagus and/or definite dysplastic changes. History of dilatation of esophageal strictures. * Subjects with erosive esophagitis (EE) as shown by endoscopy. * Evidence of uncontrolled systemic disease. Co-existing diseases affecting the esophagus. Current or history of Zollinger-Ellison syndrome. * Subject has abnormal laboratory values. * Subjects with active gastric or duodenal ulcers within 4 weeks of the first dose. * Subject known to have acquired immunodeficiency syndrome (AIDS). * Known hypersensitivity to any proton pump inhibitor (PPI), any component of Dexlansoprazole MR, or antacid. * Use of prescription or non-prescription PPIs, histamine (H2) receptor antagonists, or sucralfate. * 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. * Subjects who cannot discontinue the use of misoprostol or prokinetics * Need for continuous anticoagulant therapy. * Females who are pregnant or lactating. * History of gastrointestinal surgery except for simple oversew of ulcer. * History of cancer within 3 years prior to screening. * Subject has participated in a previous Dexlansoprazole study. * Subjects who, in the opinion of the investigator, are unable to comply with the requirements of the study or are unsuitable for any reason.
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 154 sites in the United States (US); date of first dose: 08 June 2006; date of last procedure: 11 December 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. | 317 |
| Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 4 weeks. | 315 |
| Dexlansoprazole MR 60 mg QD Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 4 weeks. | 315 |
| Total | 947 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 6 | 8 |
| Overall Study | Lack of Efficacy | 3 | 1 | 3 |
| Overall Study | Lost to Follow-up | 2 | 4 | 2 |
| Overall Study | Noncompliant | 0 | 0 | 2 |
| Overall Study | Per Investigator Request | 1 | 0 | 0 |
| Overall Study | Per Sponsor Due to High Baseline Gastrin | 0 | 1 | 0 |
| Overall Study | Per Subject Request | 1 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Unmet Inclusion/Exclusion Criteria | 3 | 1 | 5 |
| Overall Study | Withdrawal by Subject | 8 | 6 | 5 |
Baseline characteristics
| Characteristic | Placebo QD | Dexlansoprazole MR 30 mg QD | Dexlansoprazole MR 60 mg QD | Total |
|---|---|---|---|---|
| Age Continuous | 47.6 years STANDARD_DEVIATION 14.4 | 47.6 years STANDARD_DEVIATION 13.55 | 47.5 years STANDARD_DEVIATION 13.77 | 47.5 years STANDARD_DEVIATION 13.9 |
| Age, Customized 45 to <65 years | 148 participants | 149 participants | 136 participants | 433 participants |
| Age, Customized <45 years | 130 participants | 131 participants | 139 participants | 400 participants |
| Age, Customized ≥65 years | 39 participants | 35 participants | 40 participants | 114 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 62 Participants | 67 Participants | 53 Participants | 182 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 255 Participants | 248 Participants | 262 Participants | 765 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 | 0 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 7 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 37 Participants | 48 Participants | 130 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 3 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) White | 255 Participants | 267 Participants | 251 Participants | 773 Participants |
| Sex: Female, Male Female | 233 Participants | 231 Participants | 209 Participants | 673 Participants |
| Sex: Female, Male Male | 84 Participants | 84 Participants | 106 Participants | 274 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 | 34 / — | 41 / — | 36 / — |
| serious Total, serious adverse events | 1 / — | 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 | 25.0 percentage of days | Standard Deviation 25.6 |
| Dexlansoprazole MR 30 mg QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 50.3 percentage of days | Standard Deviation 33.9 |
| Dexlansoprazole MR 60 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 34.7 |
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 | 18.5 percentage of days |
| Dexlansoprazole MR 30 mg QD | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 54.9 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 | 50.0 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: 0.72941Wilcoxon (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 | 47.1 percentage of days | Standard Deviation 32.6 |
| Dexlansoprazole MR 30 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Mean | 67.6 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 | 65.0 percentage of days | Standard Deviation 34.3 |
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 | 51.7 percentage of days |
| Dexlansoprazole MR 30 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 80.8 percentage of days |
| Dexlansoprazole MR 60 mg QD | Percentage of Days Without Nighttime Heartburn During Treatment as Assessed by Daily Electronic Diary-Median | 76.9 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: 0.3146Wilcoxon (Mann-Whitney)