Efficacy and Safety of Lansoprazole on Gastric and Duodenal Ulcers in Patients Taking Nonsteroidal Anti-Inflammatory Drugs

Study Overview
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Brief Summary
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The purpose of this study is to determine whether AG-1749 (lansoprazole), once daily (QD), is effective in preventing the recurrence of gastric and duodenal ulcers in patients receiving long term treatment with nonsteroid anti-inflammatory drug, compared to gefarnate, twice daily (BID).

Detailed Description
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In Japan, nonsteroid anti-inflammatory drug is one of common prescribed drugs for patients as an analgesic antipyretic, treating symptoms of cold, antiphlogistic and management of pain with rheumatoid arthritis, osteoarthrosis, lumbago. On the other hand, this nonsteroid anti-inflammatory drug sometimes causes gastric and duodenal ulcers and this ulcer leads to the gastrointestinal bleeding which may be cause of death. The purpose of this study is to assess the efficacy of lansoprazole versus gefarnate in patients with a history of gastric or duodenal ulcers receiving daily nonsteroid anti-inflammatory medication.

Official Title
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A Study to Investigate the Preventive Effect of AG-1749 Against the Recurrence of Gastric and Duodenal Ulcers During Long-term Treatment With Nonsteroid Anti-inflammatory Drug

Conditions
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Stomach Ulcer, Duodenal Ulcer

Intervention / Treatment
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* Drug: Lansoprazole
* Drug: Gefarnate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient was on nonsteroid anti-inflammatory drug (NSAID) treatment on the day when consent was obtained, and requires the long-term continuous treatment even after treatment with the investigational drug is started. The patient was confirmed to have a history of gastric ulcer or duodenal ulcer. Exclusion Criteria: Endoscopically confirmed gastric and/or duodenal ulcers on Day 1. Endoscopically confirmed active upper gastrointestinal hemorrhage on Day 1. Current or past history of aspirin-induced asthma or hypersensitivity to NSAIDs. Past or planned surgery affecting gastric acid secretion. Clinically significant hepatic or renal disorder. Serious cardiac dysfunction, hypertension, or hematological disorder.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lansoprazole 15 mg QD<br> | Drug: Lansoprazole<br>* Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.<br>* Other names: AG-1749;|
| Active Comparator: Gefarnate 50 mg BID<br> | Drug: Gefarnate<br>* Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Gastric Ulcer and/or Duodenal Ulcer | The number of participants that developed gastric ulcer and/or duodenal ulcer at month 24 or final visit. Ulcers are defined as mucosal defect with white coating 3 mm or greater. | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 3. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 6. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 12. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 18. | 
| Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 24) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the stomach, graded on a 5 point scale (0=normal; 1= erosion/hemorrhage in one area of the stomach and <1 lesion; 2= erosion/hemorrhage in one area of the stomach with 2-5 lesions; 3= erosion/hemorrhage in two areas in the stomach/one area involves >6 lesions; 4= erosion/hemorrhage appear in three or more areas in the stomach). Erosions are mucosal defect < 3 mm. Ulcers are mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of gastric mucosal injury. | Baseline and Month 24. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 3. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 6. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 12. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 18. | 
| Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 24) | The Lanza score (partially revised) attributes the severity of induced erosive mucosal injury in the duodenum, graded on a 4 point scale (0=normal; 1= erosion and hemorrhage are localized in one area of the duodenum and < 1 lesion; 2= 2 to 5 lesions ; 3= > 6 lesions). Erosions are defined as mucosal defect < 3 mm. Ulcers are defined as mucosal defect with white coating ≥ 3 mm. Higher scores indicate greater severity of duodenal mucosal injury. | Baseline and Month 24. | 
| Number of Participants With Gastric or Duodenal Ulcer or Gastric or Duodenal Hemorrhagic Lesion (Upper Gastrointestinal Hemorrhage) | Number of participants with gastric or duodenal ulcer or gastric or duodenal hemorrhagic lesion (upper gastrointestinal hemorrhage) from baseline through month 24 or final visit. Ulcers are defined as mucosal defect with white coating 3 mm or greater. | On occurrence (up to month 24). | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 3) | The number of participants that develop postprandial pain at month 3, and number of participants that develop postprandial pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 6) | The number of participants that develop postprandial pain at month 6, and number of participants that develop postprandial pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 12) | The number of participants that develop postprandial pain at month 12, and number of participants that develop postprandial pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 18) | The number of participants that develop postprandial pain at month 18, and number of participants that develop postprandial pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 24) | The number of participants that develop postprandial pain at month 24, and number of participants that develop postprandial pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 3) | The number of participants that develop hunger and nighttime pain at month 3, and number of participants that develop hunger and nighttime pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 6) | The number of participants that develop hunger and nighttime pain at month 6, and number of participants that develop hunger and nighttime pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 12) | The number of participants that develop hunger and nighttime pain at month 12, and number of participants that develop hunger and nighttime pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 18) | The number of participants that develop hunger and nighttime pain at month 18, and number of participants that develop hunger and nighttime pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 24) | The number of participants that develop hunger and nighttime pain at month 24, and number of participants that develop hunger and nighttime pain at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 3) | The number of participants that develop the feeling of an enlarged abdomen at month 3, and number of participants that develop the feeling of an enlarged abdomen at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 6) | The number of participants that develop the feeling of an enlarged abdomen at month 6, and number of participants that develop the feeling of an enlarged abdomen at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 12) | The number of participants that develop the feeling of an enlarged abdomen at month 12, and number of participants that develop the feeling of an enlarged abdomen at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 18) | The number of participants that develop the feeling of an enlarged abdomen at month 18, and number of participants that develop the feeling of an enlarged abdomen at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 24) | The number of participants that develop the feeling of an enlarged abdomen at month 24, and number of participants that develop the feeling of an enlarged abdomen at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 3) | The number of participants that develop the feeling of nausea at month 3, and number of participants that develop the feeling of nausea at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 6) | The number of participants that develop the feeling of nausea at month 6, and number of participants that develop the feeling of nausea at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 12) | The number of participants that develop the feeling of nausea at month 12, and number of participants that develop the feeling of nausea at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 18) | The number of participants that develop the feeling of nausea at month 18, and number of participants that develop the feeling of nausea at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 24) | The number of participants that develop the feeling of nausea at month 24, and number of participants that develop the feeling of nausea at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 3) | The number of participants that develop the feeling of heartburn at month 3, and number of participants that develop the feeling of heartburn at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 6) | The number of participants that develop the feeling of heartburn at month 6, and number of participants that develop the feeling of heartburn at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 12) | The number of participants that develop the feeling of heartburn at month 12, and number of participants that develop the feeling of heartburn at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 18) | The number of participants that develop the feeling of heartburn at month 18, and number of participants that develop the feeling of heartburn at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 24) | The number of participants that develop the feeling of heartburn at month 24, and number of participants that develop the feeling of heartburn at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 3) | The number of participants that develop anorexia at month 3, and number of participants that develop anorexia at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 6) | The number of participants that develop anorexia at month 6, and number of participants that develop anorexia at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 12) | The number of participants that develop anorexia at month 12, and number of participants that develop anorexia at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 18) | The number of participants that develop anorexia at month 18, and number of participants that develop anorexia at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 24) | The number of participants that develop anorexia at month 24, and number of participants that develop anorexia at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 3) | The number of participants that experience hematemesis and melena (blood stool, black stool, tarry stool) at month 3, and number of participants that experience hematemesis and melena at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 3. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 6) | The number of participants that experience hematemesis and melena (blood stool, black stool, tarry stool) at month 6, and number of participants that experience hematemesis and melena at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 6. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 12) | The number of participants that experience hematemesis and melena (blood stool, black stool, tarry stool) at month 12, and number of participants that experience hematemesis and melena at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 12. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 18) | The number of participants that experience hematemesis and melena (blood stool, black stool, tarry stool) at month 18, and number of participants that experience hematemesis and melena at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 18. | 
| Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 24) | The number of participants that experience hematemesis and melena (blood stool, black stool, tarry stool) at month 24, and number of participants that experience hematemesis and melena at baseline. It is graded on a 4 point scale (0=none; 1=mild; 2=moderate; 3=severe). Higher scores indicate greater severity of gastrointestinal symptom. | Baseline and Month 24. | 
| Number of Participants With Adverse Events | Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug. A TEAE may also be a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing. Please see Other Adverse Events table below for TEAE listings. | Per Incidence (up to 24 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Curling Ulcer, Gastric Ulcer, Nonsteroid anti-inflammatory drug, Drug Therapy