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

Phase 3

Completed

Conditions: Stomach Ulcer
Duodenal Ulcer

Interventions: Drug: Gefarnate
Drug: Lansoprazole

Registration Number: NCT00787254

Lead Sponsor: Takeda

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 366

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gefarnate 50 mg BID	Gefarnate	-
Lansoprazole 15 mg QD	Lansoprazole	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Gastric Ulcer and/or Duodenal Ulcer	24 Months	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3)	Baseline and 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.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6)	Baseline and 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.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12)	Baseline and 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.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18)	Baseline and 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.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 24)	Baseline and 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.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3)	Baseline and 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.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6)	Baseline and 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.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12)	Baseline and 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.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18)	Baseline and 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.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 24)	Baseline and 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.
Number of Participants With Gastric or Duodenal Ulcer or Gastric or Duodenal Hemorrhagic Lesion (Upper Gastrointestinal Hemorrhage)	On occurrence (up to month 24).	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.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 24)	Baseline and 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.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 24)	Baseline and 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.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 24)	Baseline and 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.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 24)	Baseline and 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.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 24)	Baseline and 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.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 24)	Baseline and 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.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 3)	Baseline and 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.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 6)	Baseline and 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.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 12)	Baseline and 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.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 18)	Baseline and 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.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 24)	Baseline and 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.
Number of Participants With Adverse Events	Per Incidence (up to 24 months).	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.