Erosive Esophagitis
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine the efficacy of dexlansoprazole compared to lansoprazole in healing erosive esophagitis (EE) in Chinese participants.
Detailed description
The drug being tested in this study is called dexlansoprazole. Dexlansoprazole is being tested to treat people who have EE. This study will look at erosive esophageal healing in people who take dexlansoprazole. The study will enroll approximately 450 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 60 mg * Lansoprazole 30 mg After 8 weeks of treatment, participants will be evaluated to assess esophageal healing. If the EE is healed participants will be randomly assigned to one of two different treatment groups with 1:1 ratio: * 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. This multi-center trial will be conducted in China. The overall time to participate in this study is up to 39 weeks. Participants will make 7 visits to the clinic, and will be contacted by telephone 5 to 10 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGDexlansoprazole
Dexlansoprazole delayed-release capsules.
DRUGLansoprazole
Lansoprazole capsules.
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\. Has endoscopically confirmed EE as defined by the LA Classification Grading System (A-D).
Exclusion criteria
1. Participant is required to take excluded medications, or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study evaluation period. 2. Has a hypersensitivity to any proton pump inhibitor (PPI) (including, but not limited to, lansoprazole, omeprazole, rabeprazole, pantoprazole, esomeprazole or ilaprazole), any component of dexlansoprazole, or antacid (example, magnesium trisilicate or similar antacid). 3. Had 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. 4. Has a known history or any suspicious Barrett's esophagus with dysplastic changes seen during screening endoscopy. 5. 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 (\>12 doses per month) of non steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) NSAIDs within 30 days prior to the Screening Period and throughout the study. 6. 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). 7. 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. 8. Participant is known to have the 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). 9. Has current Zollinger-Ellison syndrome (gastric acid hyper secretion) or a history of gastric acid hypersecretion. 10. Participant is scheduled for surgery that requires hospitalization or requires surgical treatment during his/her participation in the study. 11. 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. 12. Has a history of alcohol or drug abuse (defined as any illicit drug use), or drug addiction in the 12 months prior to Screening. 13. The 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 |
|---|---|---|
| Healing Period: Percentage of Participants With Complete Healing of EE at Week 8 | Week 8 | Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the Los Angeles (LA) classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (\>=1 mucosal break no longer than 5 millimeter \[mm\] that does not extend between the tops of 2 mucosal folds); Grade B (\>=1 mucosal break greater than \[\>\] 5 mm that does not extend between the tops of 2 mucosal folds); Grade C (\>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves \<75 percent (%) of the circumference); Grade D (\>=1 mucosal break which involves \>=75% of the circumference). Healing is defined as LA Grade O. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6 | Month 6 | Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the LA classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (\>=1 mucosal break no longer than 5 mm that does not extend between the tops of 2 mucosal folds); Grade B (\>=1 mucosal break \>5 mm that does not extend between the tops of 2 mucosal folds); Grade C (\>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves \<75% of the circumference); Grade D (\>=1 mucosal break which involves \>=75% of the circumference). Healing is defined as LA Grade O. |
Countries
China
Participant flow
Recruitment details
Participants took part in the study at 8 investigative sites in China from 21 December 2016 to 06 November 2017.
Pre-assignment details
Participants with erosive esophagitis (EE) were enrolled to receive: lansoprazole 30 milligram (mg) or dexlansoprazole 60 mg in Healing Period and dexlansoprazole 30 mg or Placebo in Maintenance Period. Study was terminated since compound was not expected to provide sufficient additional benefit to participants over currently available therapies.
Participants by arm
| Arm | Count |
|---|---|
| Healing Period: Lansoprazole 30 mg Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period. | 20 |
| Healing Period: Dexlansoprazole 60 mg Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period. | 17 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Healing Period (up to Week 8) | Adverse Event | 1 | 0 | 0 | 0 |
| Healing Period (up to Week 8) | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Maintenance Period (up to Month 6) | Adverse Event | 0 | 0 | 1 | 0 |
| Maintenance Period (up to Month 6) | Relapse of EE | 0 | 0 | 4 | 1 |
| Maintenance Period (up to Month 6) | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Healing Period: Dexlansoprazole 60 mg | Healing Period: Lansoprazole 30 mg |
|---|---|---|---|
| Age, Continuous | 48.4 years STANDARD_DEVIATION 12.8 | 47.4 years STANDARD_DEVIATION 11.03 | 49.4 years STANDARD_DEVIATION 14.35 |
| Baseline Body Mass Index (BMI) | 23.905 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.9452 | 24.606 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.5321 | 23.310 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.2623 |
| BMI Categories 25 to <30 kg/m^2 | 12 Participants | 7 Participants | 5 Participants |
| BMI Categories Greater than or equal to (>=) 30 kg/m^2 | 1 Participants | 1 Participants | 0 Participants |
| BMI Categories Less than (<) 25 kg/m^2 | 24 Participants | 9 Participants | 15 Participants |
| Height | 166.99 centimeter (cm) STANDARD_DEVIATION 8.131 | 167.82 centimeter (cm) STANDARD_DEVIATION 8.346 | 166.28 centimeter (cm) STANDARD_DEVIATION 8.091 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 37 Participants | 17 Participants | 20 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 | 37 Participants | 17 Participants | 20 Participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 28 Participants | 14 Participants | 14 Participants |
| Weight | 66.89 kilogram (kg) STANDARD_DEVIATION 10.683 | 69.44 kilogram (kg) STANDARD_DEVIATION 11.19 | 64.73 kilogram (kg) STANDARD_DEVIATION 10.002 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 17 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 15 / 20 | 7 / 17 | 1 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 20 | 0 / 17 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Healing Period: Percentage of Participants With Complete Healing of EE at Week 8
Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the Los Angeles (LA) classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (\>=1 mucosal break no longer than 5 millimeter \[mm\] that does not extend between the tops of 2 mucosal folds); Grade B (\>=1 mucosal break greater than \[\>\] 5 mm that does not extend between the tops of 2 mucosal folds); Grade C (\>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves \<75 percent (%) of the circumference); Grade D (\>=1 mucosal break which involves \>=75% of the circumference). Healing is defined as LA Grade O.
Time frame: Week 8
Population: The FAS-H included all randomized participants who had documented EE at screening and had received at least 1 dose of study drug during the first 8 weeks of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healing Period: Lansoprazole 30 mg | Healing Period: Percentage of Participants With Complete Healing of EE at Week 8 | 85.0 percentage of participants |
| Healing Period: Dexlansoprazole 60 mg | Healing Period: Percentage of Participants With Complete Healing of EE at Week 8 | 82.4 percentage of participants |
Comparison: Healing Period: Dexlansoprazole 60 mg versus Healing Period: Lansoprazole 30 mg95% CI: [-26.59, 21.3]
Secondary
Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6
Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the LA classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (\>=1 mucosal break no longer than 5 mm that does not extend between the tops of 2 mucosal folds); Grade B (\>=1 mucosal break \>5 mm that does not extend between the tops of 2 mucosal folds); Grade C (\>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves \<75% of the circumference); Grade D (\>=1 mucosal break which involves \>=75% of the circumference). Healing is defined as LA Grade O.
Time frame: Month 6
Population: The full analysis set for the maintenance period (FAS-M) included all participants with healed EE by week 8 who were randomized and received at least 1 dose of study drug during 6 months of maintenance treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healing Period: Lansoprazole 30 mg | Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6 | 0 percentage of participants |
| Healing Period: Dexlansoprazole 60 mg | Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6 | 25 percentage of participants |