Gastroesophageal Reflux Disease, Heartburn
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine the efficacy and safety of dexlansoprazole compared to placebo in relief of daytime and nighttime heartburn over 4 weeks in Chinese participants with symptomatic non-erosive Gastroesophageal Reflux Disease (GERD).
Detailed description
The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to treat heartburn in people who have non-erosive gastroesophageal reflux disease (GERD). This study will look at heartburn relief in people who take dexlansoprazole. The study will enroll approximately 200 participants. Participants will be randomly assigned to one of the two treatment groups with 1:1 ratio -which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Dexlansoprazole 30 mg * Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient. All participants will be asked to take one capsule at the same time each day throughout the study, and will be asked to record any time they have heartburn symptoms in a diary. This multi-center trial will be conducted in China. The overall time to participate in this study is up to 7 weeks. Participants will make 4 visits to the clinic, and will be contacted by telephone 5 to 10 days after the last dose of study drug for a follow-up assessment.
Interventions
DRUGDexlansoprazole
Dexlansoprazole delayed-release capsule
DRUGPlacebo
Dexlansoprazole placebo-matching capsules
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants identifying their main symptom as a burning feeling in the mid-epigastric area and/or chest area (that is, heartburn). 2. Must have a history of symptomatic GERD for 6 months or longer prior to Screening with GERD symptoms that were responsive to acid-suppressive therapy. 3. Must have episodes of heartburn for 4 or more days during the 7 days prior to Day -1 as recorded in the eDiary.
Exclusion criteria
1. Has a history of cancer (except basal cell carcinoma of the skin), that has not been in remission for at least 5 years prior to Screening. 2. Has a known history of Barrett's esophagus with dysplastic changes or any changes suspicious Barrett's seen during screening endoscopy. 3. Participant developed acute upper gastrointestinal bleeding, gastric ulcer (a mucosal defect with white coating) or duodenal ulcer (a mucosal defect with white coating), within 30 days before the start of the Screening Visit (with the possible inclusion of those with gastric or duodenal erosion). The participant requires chronic use (greater than \[\>\] 12 doses per month) of nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) NSAIDs within 30 days prior to the Screening Period and throughout the study. 4. Has comorbidities that could affect the esophagus (eosinophilic esophagitis, esophageal varices, scleroderma, viral or fungal infection, esophageal strictures); a history of radiotherapy or cryotherapy of the esophagus; and a history of corrosive or physiochemical injury (with the possible inclusion in the study of those with Schatzki's ring). 5. Has a history of surgical procedures that may affect the esophagus (example, fundoplication and mechanical dilatation for esophageal strictures) or a history of gastric or duodenal surgery other than endoscopic removal of benign polyps. 6. Has erosive esophagitis (EE) as shown by endoscopy, during the Screening Period. 7. Is known to have acquired immunodeficiency syndrome (AIDS) or hepatitis, including hepatitis virus carriers: (that is, hepatitis B surface antigen HBs-antigen (HBsAg) positive or hepatitis C virus (HCV)-antibody positive). 8. Has current or historical evidence of Zollinger-Ellison syndrome or a history of gastric acid hypersecretion. 9. Is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study. 10. Has donated or lost \>300 milliliter (mL) blood volume, undergone plasmapheresis, or has had a transfusion of any blood product within 90 days prior to the first dose of study drug. 11. Has a history of alcohol abuse (defined as any illicit drug use), or drug addiction in the 12 months prior to Screening. 12. Participant with positive serology result of Helicobacter pylori (H. pylori) that needs eradication therapy during the study participation period as anticipated by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment | Up to Week 4 | The percentage of days with neither daytime nor nighttime heartburn was equal to (=) (the days that were heartburn-free during the treatment period) / (total number of days for which either a daytime or nighttime result was marked during treatment period)\*100 percent (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days Without Nighttime Heartburn During Treatment | Up to Week 4 | The percentage of days without nighttime heartburn was = (the days that were heartburn-free during the treatment period) / (total number of days for which nighttime result was marked during treatment period)\*100%. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 20 investigative sites in China from 27 December 2016 to 19 April 2018.
Pre-assignment details
Participants with diagnosis of symptomatic nonerosive gastroesophageal reflux disease (GERD) were enrolled in 1 of the 2 treatment groups: to receive dexlansoprazole 30 mg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dexlansoprazole placebo-matching capsule, orally, once daily for up to 4 weeks. | 108 |
| Dexlansoprazole 30 mg Dexlansoprazole 30 mg, capsule, orally, once daily for up to 4 weeks. | 107 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Randomized but not Treated | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | Dexlansoprazole 30 mg | Placebo |
|---|---|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 12.98 | 43.6 years STANDARD_DEVIATION 13.24 | 45.1 years STANDARD_DEVIATION 12.73 |
| Body mass index | 23.819 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.5002 | 23.701 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.5768 | 23.935 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.4352 |
| Helicobacter pylori status Negative | 134 Participants | 67 Participants | 67 Participants |
| Helicobacter pylori status Positive | 81 Participants | 40 Participants | 41 Participants |
| Number of days with day and nighttime heartburn between study days -8 to -2 | 6.1 days STANDARD_DEVIATION 1.17 | 6.1 days STANDARD_DEVIATION 1.06 | 6.1 days STANDARD_DEVIATION 1.27 |
| Number of days with daytime heartburn between study days -8 to -2 | 5.5 days STANDARD_DEVIATION 1.54 | 5.3 days STANDARD_DEVIATION 1.61 | 5.6 days STANDARD_DEVIATION 1.45 |
| Number of days with nighttime heartburn between study days -8 to -2 | 5.2 days STANDARD_DEVIATION 1.71 | 5.3 days STANDARD_DEVIATION 1.6 | 5.2 days STANDARD_DEVIATION 1.83 |
| Number of days with rescue medication use | 1.3 days STANDARD_DEVIATION 2.19 | 0.9 days STANDARD_DEVIATION 1.48 | 1.7 days STANDARD_DEVIATION 2.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 215 Participants | 107 Participants | 108 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 215 Participants | 107 Participants | 108 Participants |
| Severity of GERD symptoms: acid regurgitation Mild | 85 Participants | 43 Participants | 42 Participants |
| Severity of GERD symptoms: acid regurgitation Moderate | 51 Participants | 24 Participants | 27 Participants |
| Severity of GERD symptoms: acid regurgitation None | 60 Participants | 33 Participants | 27 Participants |
| Severity of GERD symptoms: acid regurgitation Severe | 18 Participants | 6 Participants | 12 Participants |
| Severity of GERD symptoms: acid regurgitation Very Severe | 1 Participants | 1 Participants | 0 Participants |
| Severity of GERD symptoms: belching Mild | 75 Participants | 37 Participants | 38 Participants |
| Severity of GERD symptoms: belching Moderate | 15 Participants | 6 Participants | 9 Participants |
| Severity of GERD symptoms: belching None | 121 Participants | 62 Participants | 59 Participants |
| Severity of GERD symptoms: belching Severe | 4 Participants | 2 Participants | 2 Participants |
| Severity of GERD symptoms: belching Very Severe | 0 Participants | 0 Participants | 0 Participants |
| Severity of GERD symptoms: dysphagia Mild | 11 Participants | 4 Participants | 7 Participants |
| Severity of GERD symptoms: dysphagia Moderate | 0 Participants | 0 Participants | 0 Participants |
| Severity of GERD symptoms: dysphagia None | 204 Participants | 103 Participants | 101 Participants |
| Severity of GERD symptoms: dysphagia Severe | 0 Participants | 0 Participants | 0 Participants |
| Severity of GERD symptoms: dysphagia Very Severe | 0 Participants | 0 Participants | 0 Participants |
| Severity of GERD symptoms: epigastric pain Mild | 27 Participants | 16 Participants | 11 Participants |
| Severity of GERD symptoms: epigastric pain Moderate | 4 Participants | 2 Participants | 2 Participants |
| Severity of GERD symptoms: epigastric pain None | 183 Participants | 88 Participants | 95 Participants |
| Severity of GERD symptoms: epigastric pain Severe | 1 Participants | 1 Participants | 0 Participants |
| Severity of GERD symptoms: epigastric pain Very Severe | 0 Participants | 0 Participants | 0 Participants |
| Severity of GERD symptoms: heartburn Mild | 62 Participants | 33 Participants | 29 Participants |
| Severity of GERD symptoms: heartburn Moderate | 111 Participants | 55 Participants | 56 Participants |
| Severity of GERD symptoms: heartburn None | 0 Participants | 0 Participants | 0 Participants |
| Severity of GERD symptoms: heartburn Severe | 39 Participants | 17 Participants | 22 Participants |
| Severity of GERD symptoms: heartburn Very Severe | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 125 Participants | 60 Participants | 65 Participants |
| Sex: Female, Male Male | 90 Participants | 47 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 107 |
| other Total, other adverse events | 15 / 108 | 9 / 107 |
| serious Total, serious adverse events | 0 / 108 | 1 / 107 |
Outcome results
Primary
Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment
The percentage of days with neither daytime nor nighttime heartburn was equal to (=) (the days that were heartburn-free during the treatment period) / (total number of days for which either a daytime or nighttime result was marked during treatment period)\*100 percent (%).
Time frame: Up to Week 4
Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had post-baseline (post Day-1) data for the appropriate efficacy variables.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment | 32.67 percentage of days |
| Dexlansoprazole 30 mg | Percentage of Days With Neither Daytime Nor Nighttime Heartburn During Treatment | 51.72 percentage of days |
p-value: 0.057Wilcoxon rank-sum test
Secondary
Percentage of Days Without Nighttime Heartburn During Treatment
The percentage of days without nighttime heartburn was = (the days that were heartburn-free during the treatment period) / (total number of days for which nighttime result was marked during treatment period)\*100%.
Time frame: Up to Week 4
Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had post-baseline (post Day-1) data for the appropriate efficacy variables.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percentage of Days Without Nighttime Heartburn During Treatment | 54.67 percentage of days |
| Dexlansoprazole 30 mg | Percentage of Days Without Nighttime Heartburn During Treatment | 67.86 percentage of days |
p-value: 0.268Wilcoxon rank-sum test