Trial Outcomes & Findings for Efficacy and Safety of Lansoprazole on Gastric and Duodenal Ulcers in Patients Taking Nonsteroidal Anti-Inflammatory Drugs (NCT NCT00787254)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

366 participants

Primary outcome timeframe

24 Months

Results posted on

2012-02-03

Participant Flow

Participants were enrolled at sites in Japan from April 2007 to May 2009.

Participants were enrolled in either lansoprazole, once daily (QD) or gefarnate, twice daily (BID) treatment groups. NSAID = Nonsteroidal anti-inflammatory drug.

Participant milestones

Participant milestones
Measure	Lansoprazole 15 mg QD Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Overall Study STARTED	185	181
Overall Study COMPLETED	109	99
Overall Study NOT COMPLETED	76	82

Reasons for withdrawal

Reasons for withdrawal
Measure	Lansoprazole 15 mg QD Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Overall Study Adverse Event	24	23
Overall Study Protocol Violation	26	23
Overall Study Withdrawal by Subject	16	11
Overall Study Lack of Efficacy	4	15
Overall Study NSAIDs discontinuation	1	2
Overall Study Institution closed	1	0
Overall Study Physician Decision	4	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lansoprazole 15 mg QD n=185 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=181 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.	Total n=366 Participants Total of all reporting groups
Age, Customized ≤39 years	7 participants 3.8 • n=99 Participants	6 participants 3.3 • n=107 Participants	13 participants 3.6 • n=206 Participants
Age, Customized Between 40 and 49 years	18 participants 9.7 • n=99 Participants	13 participants 7.2 • n=107 Participants	31 participants 8.5 • n=206 Participants
Age, Customized Between 50 and 59 years	38 participants 20.5 • n=99 Participants	43 participants 23.8 • n=107 Participants	81 participants 22.1 • n=206 Participants
Age, Customized Between 60 and 64 years	33 participants 17.8 • n=99 Participants	29 participants 16.0 • n=107 Participants	62 participants 16.9 • n=206 Participants
Age, Customized Between 65 and 69 years	33 participants 17.8 • n=99 Participants	30 participants 16.6 • n=107 Participants	63 participants 17.2 • n=206 Participants
Age, Customized Between 70 and 79 years	43 participants 23.2 • n=99 Participants	48 participants 26.5 • n=107 Participants	91 participants 24.9 • n=206 Participants
Age, Customized ≤80 years	13 participants 7.0 • n=99 Participants	12 participants 6.6 • n=107 Participants	25 participants 6.8 • n=206 Participants
Sex: Female, Male Female	112 Participants n=99 Participants	107 Participants n=107 Participants	219 Participants n=206 Participants
Sex: Female, Male Male	73 Participants n=99 Participants	74 Participants n=107 Participants	147 Participants n=206 Participants
Region of Enrollment Japan	185 participants n=99 Participants	181 participants n=107 Participants	366 participants n=206 Participants

PRIMARY outcome

Timeframe: 24 Months

Population: Participants not taking investigational drug were not included.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=183 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=181 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Number of Participants With Gastric Ulcer and/or Duodenal Ulcer	15 participants	46 participants

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=167 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=154 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3)	-0.114 scores on a scale Standard Deviation 1.020	0.429 scores on a scale Standard Deviation 1.318

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=116 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=85 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6)	-0.319 scores on a scale Standard Deviation 1.060	0.188 scores on a scale Standard Deviation 1.268

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=78 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=62 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12)	-0.231 scores on a scale Standard Deviation 1.299	0.048 scores on a scale Standard Deviation 1.137

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=37 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=18 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18)	-0.162 scores on a scale Standard Deviation 1.280	-0.278 scores on a scale Standard Deviation 1.227

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=5 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=2 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Gastric Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 24)	-0.800 scores on a scale Standard Deviation 1.304	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=167 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=155 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 3)	-0.102 scores on a scale Standard Deviation 0.499	0.142 scores on a scale Standard Deviation 0.649

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=116 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=86 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 6)	-0.095 scores on a scale Standard Deviation 0.527	0.047 scores on a scale Standard Deviation 0.373

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=79 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=62 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 12)	-0.177 scores on a scale Standard Deviation 0.675	0.048 scores on a scale Standard Deviation 0.381

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=37 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=18 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 18)	-0.297 scores on a scale Standard Deviation 0.812	-0.056 scores on a scale Standard Deviation 0.539

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=5 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=2 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Duodenal Mucosal Injury Assessed by Lanza Score (Partially Revised) (Month 24)	-0.200 scores on a scale Standard Deviation 0.447	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.

SECONDARY outcome

Timeframe: On occurrence (up to month 24).

Population: On days where participants did not have an occurrence of gastric or duodenal ulcer or gastric or duodenal hemorrhagic lesion (upper gastrointestinal hemorrhage) and who also underwent endoscopic examination were considered censored dates. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=183 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=181 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Number of Participants With Gastric or Duodenal Ulcer or Gastric or Duodenal Hemorrhagic Lesion (Upper Gastrointestinal Hemorrhage)	15 participants	52 participants

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 3)	-0.006 scores on a scale Standard Deviation 0.178	0.014 scores on a scale Standard Deviation 0.319

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 6)	0.027 scores on a scale Standard Deviation 0.285	0.000 scores on a scale Standard Deviation 0.347

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 12)	-0.014 scores on a scale Standard Deviation 0.208	-0.020 scores on a scale Standard Deviation 0.249

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 18)	0.000 scores on a scale Standard Deviation 0.000	0.000 scores on a scale Standard Deviation 0.000

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Postprandial Pain Gastrointestinal Symptom (Month 24)	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 3)	-0.044 scores on a scale Standard Deviation 0.326	0.014 scores on a scale Standard Deviation 0.400

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 6)	0.009 scores on a scale Standard Deviation 0.393	-0.036 scores on a scale Standard Deviation 0.424

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 12)	-0.029 scores on a scale Standard Deviation 0.416	-0.061 scores on a scale Standard Deviation 0.317

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 18)	0.000 scores on a scale Standard Deviation 0.000	0.000 scores on a scale Standard Deviation 0.447

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hunger and Nighttime Pain Gastrointestinal Symptom (Month 24)	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 3)	-0.025 scores on a scale Standard Deviation 0.318	-0.014 scores on a scale Standard Deviation 0.452

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 6)	0.000 scores on a scale Standard Deviation 0.381	-0.048 scores on a scale Standard Deviation 0.408

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 12)	-0.057 scores on a scale Standard Deviation 0.336	-0.204 scores on a scale Standard Deviation 0.407

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 18)	-0.056 scores on a scale Standard Deviation 0.416	0.000 scores on a scale Standard Deviation 0.447

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Enlarged Abdomen Gastrointestinal Symptom (Month 24)	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 3)	-0.006 scores on a scale Standard Deviation 0.239	0.007 scores on a scale Standard Deviation 0.308

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 6)	0.009 scores on a scale Standard Deviation 0.286	-0.012 scores on a scale Standard Deviation 0.245

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 12)	-0.043 scores on a scale Standard Deviation 0.204	-0.041 scores on a scale Standard Deviation 0.200

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 18)	0.000 scores on a scale Standard Deviation 0.000	-0.091 scores on a scale Standard Deviation 0.302

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Nausea Gastrointestinal Symptom (Month 24)	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 3)	-0.057 scores on a scale Standard Deviation 0.378	0.058 scores on a scale Standard Deviation 0.625

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 6)	-0.027 scores on a scale Standard Deviation 0.476	-0.095 scores on a scale Standard Deviation 0.428

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 12)	-0.114 scores on a scale Standard Deviation 0.363	-0.102 scores on a scale Standard Deviation 0.510

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 18)	-0.056 scores on a scale Standard Deviation 0.236	0.091 scores on a scale Standard Deviation 0.302

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Feeling of Heartburn Gastrointestinal Symptom (Month 24)	-1.000 scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 3)	0.006 scores on a scale Standard Deviation 0.138	0.022 scores on a scale Standard Deviation 0.283

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 6)	0.036 scores on a scale Standard Deviation 0.187	0.024 scores on a scale Standard Deviation 0.268

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 12)	0.014 scores on a scale Standard Deviation 0.208	-0.020 scores on a scale Standard Deviation 0.143

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 18)	0.056 scores on a scale Standard Deviation 0.236	0.000 scores on a scale Standard Deviation 0.000

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Anorexia Gastrointestinal Symptom (Month 24)	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: Baseline and Month 3.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=158 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=138 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 3)	0.006 scores on a scale Standard Deviation 0.080	-0.007 scores on a scale Standard Deviation 0.085

SECONDARY outcome

Timeframe: Baseline and Month 6.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=111 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=84 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 6)	0.000 scores on a scale Standard Deviation 0.000	0.012 scores on a scale Standard Deviation 0.109

SECONDARY outcome

Timeframe: Baseline and Month 12.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=70 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=49 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 12)	0.043 scores on a scale Standard Deviation 0.359	0.000 scores on a scale Standard Deviation 0.000

SECONDARY outcome

Timeframe: Baseline and Month 18.

Population: Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=18 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=11 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 18)	0.000 scores on a scale Standard Deviation 0.000	0.000 scores on a scale Standard Deviation 0.000

SECONDARY outcome

Timeframe: Baseline and Month 24.

Population: No test was performed when the number of cases was 5 or less. Values are from the Full Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=1 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Change From Baseline in Severity of Hematemesis and Melena Gastrointestinal Symptom (Month 24)	NA scores on a scale Standard Deviation NA No test was performed when the number of cases was 5 or less.	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Lansoprazole 15 mg QD n=183 Participants Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=181 Participants Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Number of Participants With Adverse Events Serious adverse event	29 participants	17 participants
Number of Participants With Adverse Events Adverse Event	154 participants	125 participants
Number of Participants With Adverse Events Adverse event (Frequency ≥5%)	83 participants	64 participants
Number of Participants With Adverse Events Adverse event related to the study drug	28 participants	28 participants
Number of Participants With Adverse Events Serious adverse event related to the study drug	2 participants	1 participants

Adverse Events

Lansoprazole 15 mg QD

Serious events: 29 serious events

Other events: 83 other events

Deaths: 0 deaths

Gefarnate 50 mg BID

Serious events: 17 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Lansoprazole 15 mg QD n=183 participants at risk Lansoprazole 15 mg, capsules, orally, once daily and gefarnate placebo-matching capsules, orally, twice daily for up to 6 to 24 months.	Gefarnate 50 mg BID n=181 participants at risk Gefarnate 50 mg, capsules, orally, twice daily and lansoprazole placebo-matching capsules, orally, once daily for up to 6 to 24 months.
Infections and infestations Nasopharyngitis	27.9% 51/183 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	20.4% 37/181 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhea	10.4% 19/183 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.8% 5/181 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Reflux esophagitis	2.2% 4/183 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.6% 12/181 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	5.5% 10/183 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.5% 10/181 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	6.6% 12/183 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.5% 10/181 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Eczema	5.5% 10/183 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.8% 5/181 • Adverse events were summarized by onset date occurring on or after the first dose of double-blind study medication, and up to 24 months after the permanent discontinuation of the double-blind study medication. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Sr. VP Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The clinical trial contract states that information should never be disclosed without prior consent of the sponsor, although it does not specify the number of days during which disclosure of information is limited.
Publication restrictions are in place

Restriction type: OTHER