Safety and Efficacy of Lansoprazole in Patients With Reflux Disease

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01135368
• Collaborator: (none)
• Enrollment: 506
• Arm: 1
• Duration (Months): 75

Study Details

Study Description

Brief Summary

The purpose of this study is to measure the safety, efficacy and quality of life of lansoprazole in patients with reflux disease over a five year period.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux	Drug: Lansoprazole	Phase 4

Detailed Description

Lansoprazole is currently approved in Germany for the treatment of erosive reflux esophagitis and active duodenal and gastric ulcer disease, and for long-term treatment including maintenance of healed reflux esophagitis and duodenal ulcer disease and treatment of pathological hypersecretory conditions such as Zollinger-Ellison syndrome.

This study was conducted to evaluate the safety, efficacy and quality of life of patients receiving up to five years of treatment with lansoprazole.

Study Design

• Study Type: Interventional
• Actual Enrollment: 506 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Lansoprazole in Patients With Reflux Disease. An Open, Single Arm, Long-term Study
• Study Start Date: Jun 1, 2002
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lansoprazole Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.	Drug: Lansoprazole; Lansoprazole capsules; Other Names: Prevacid Helicid Zoton Inhibitol Agopton AG-1749

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Reflux Disease Symptom - Heartburn [Baseline and Week 8]

   Heartburn symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

2. Change From Baseline in Reflux Disease Symptoms - Acid Regurgitation [Baseline and Week 8]

   Acid regurgitation symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

3. Change From Baseline in Reflux Disease Symptom - Difficulty Swallowing [Baseline and Week 8]

   Difficulty swallowing symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

4. Change From Baseline in Reflux Disease Symptom - Pain in Upper Abdomen [Baseline and Week 8]

   Pain in the upper abdomen symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

5. Change From Baseline in Reflux Disease Symptom - Nausea & Vomiting [Baseline and Week 8]

   Nausea and vomiting symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

6. Change From Baseline in Reflux Disease Symptom - Cough & Sore Throat [Baseline and Week 8]

   Cough and sore throat symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.

7. Change From Baseline in Endoscopic Healing of Erosive Reflux Disease as Assessed by Endoscopy [Baseline and Week 8]

   Los Angeles Classification is used to grade the extension of changes in the oesophagus induced by reflux disease (Grade 0: normal aspect of mucosa; Grade A: ≥1 mucosal breaks no longer than 5 mm; Grade B: ≥1 mucosal breaks >5 mm long; Grade C: mucosal breaks extending between tops of two or more mucosal folds but are <75% of the circumference; Grade D: mucosal breaks ≥75% of the circumference). Healed defined as anything less than Grade A criteria. The shift table below summarizes the individual transitions in Los Angeles classification between Baseline (table columns) and Week 8 (table rows).

Secondary Outcome Measures

1. Change From Baseline in Enterochromaffin-like Cell Hyperplasia [Baseline and Year 5]

   Enterochromaffin-like (ECL) cells were evaluated and classified by histopathological examinations as Normal, Simple (diffuse) hyperplasia, or Linear, chain producing hyperplasia. The shift table below summarizes the individual transitions in ECL-cell classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows) for all patients.

2. Change From Baseline in Antrum Atrophy [Baseline and Year 5]

   Atrophy was assessed by histopathological examination of cells biopsied from the antrum and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in atrophy classification (mild, moderate, severe or none) between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

3. Change From Baseline in Corpus Atrophy [Baseline and Year 5]

   Atrophy was assessed by histopathological examination of cells biopsied from the corpus and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in atrophy classification (mild, moderate, severe or none) between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

4. Change From Baseline in Average Antrum Chronic Inflammation Score [Baseline and Year 5]

   Chronic inflammation of the antrum was assessed by histopathology and graded according to the Sydney classification: 0 = None; 1 = mild; 2 = moderate; 3 = Severe

5. Change From Baseline in Corpus Chronic Inflammation Score [Baseline and Year 5]

   Chronic inflammation of the corpus was assessed by histopathology and graded according to the Sydney classification: 0 = None; 1 = mild; 2 = moderate; 3 = Severe.

6. Change From Baseline in Antrum Intestinal Metaplasia [Baseline and Year 5]

   Intestinal metaplasia was assessed by biopsy and histopathological examination of the antrum and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in intestinal metaplasia classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

7. Change From Baseline in Corpus Intestinal Metaplasia [Baseline and Year 5]

   Intestinal metaplasia was assessed by biopsy and histopathological examination of the corpus and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in intestinal metaplasia classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

8. Change From Baseline in Blood Analysis - Testosterone [Baseline and Year 5]

   The change between testosterone measured at year 5 in males including final visit and Testosterone measured at baseline.

9. Change From Baseline in Blood Analysis - Luteinizing Hormone [Baseline and Year 5]

   The change between luteinizing hormone measured at year 5 in males including final visit and luteinizing hormone measured at baseline.

10. Change From Baseline in Blood Analysis - Follicle Stimulating Hormone [Baseline and Year 5.]

    The change between follicle stimulating hormone (FSH) measured at year 5 in males including final visit and follicle stimulating hormone measured at baseline.

11. Ophthalmologic Examination - Visual Acuity [Baseline and Year 5]

    Visual Acuity was measured using the Snellen eye chart at a distance of 6 meters. Acuity is expressed as a ratio of the test distance (6 M) / the distance the average eye can see the letters on a certain line of the eye chart. Visual acuity of 1 is normal; an individual with acuity of 0.5 could only recognize an object at half the distance compared to an individual with normal acuity.

12. Change From Baseline in Ophthalmologic Examination - Adaptation Without Glare [Baseline and Year 5]

    Adaptation is the ability of the eye to adjust to various levels of darkness and light. Normal and pathological status of adaptation without glare was defined as follows: Normal status: Contrast between 1:0.05 and 1:23.5. Pathological status: Contrast = 0 or contrast > 1:23.5. The shift table below summarizes the individual transitions in the classification of adaptation without glare between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

13. Change From Baseline in Ophthalmologic Examination - Adaptation With Glare [Baseline and Year 5]

    Adaptation is the ability of the eye to adjust to various levels of darkness and light. Normal and pathological status of adaptation with glare was defined as follows: Normal status: Contrast between 1:0.05 and 1:23.5. Pathological status: Contrast = 0 or contrast > 1:23.5. The shift table below summarizes the individual transitions in the classification of adaptation with glare between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

14. Change From Baseline in Ophthalmologic Examination - Accommodation [Baseline and Year 5]

    Accommodation is the adjustment of the focal length of the eye lens to keep an object in focus on the retina as its distance from the eye varies, and is measured in diopters: Diopters = 1/(focal length).

15. Change From Baseline in Ophthalmologic Examination - Color Vision [Baseline and Year 5]

    Color vision was assessed by an Ophthalmologist and classified as normal or pathological. Pathological findings include abnormal color vision tests, color blindness and anomalous quotient. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in color vision classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

16. Change From Baseline in Ophthalmologic Examination - Cornea Assessment of Right Eye [Baseline and Year 5]

    The cornea of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, corneal degeneration, opacity, scars or deposits. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in corneal classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

17. Change From Baseline in Ophthalmologic Examination - Cornea Assessment of Left Eye [Baseline and Year 5]

    The cornea of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, corneal degeneration, opacity, scars or deposits. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in corneal classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

18. Change From Baseline in Ophthalmologic Examination - Lens Assessment of Right Eye [Baseline and Year 5]

    The lens of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, lenticular opacities, vacuoles or pseudophakia. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in lens classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

19. Change From Baseline in Ophthalmologic Examination - Lens Assessment of Left Eye [Baseline and Year 5]

    The lens of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, lenticular opacities, vacuoles or pseudophakia. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in lens classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

20. Change From Baseline in Ophthalmologic Examination - Vitreous Body Assessment of Right Eye [Baseline and Year 5]

    The vitreous body of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as myodesopsia, vitreous opacities, degeneration, detachment or prolapse. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in vitreous body classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

21. Change From Baseline in Ophthalmologic Examination - Vitreous Body Assessment of Left Eye [Baseline and Year 5]

    The vitreous body of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as myodesopsia, vitreous opacities, degeneration, detachment or prolapse. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in vitreous body classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

22. Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Aspect of the Right Eye [Baseline and Year 5]

    The retinal aspect of the right eye (such as color anomalies) was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as deep red ocular fundus, fundus myopicus, retinal disorders, exudates or pigmentation. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal aspect classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

23. Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Aspect of the Left Eye [Baseline and Year 5]

    The retinal aspect of the left eye (such as color anomalies) was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as deep red ocular fundus, fundus myopicus, retinal disorders, exudates or pigmentation. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal aspect classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

24. Change From Baseline in Ophthalmologic Examination - Assessment of Optic Nerve and Papilla of the Right Eye [Baseline and Year 5]

    The optic nerve and papilla of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as optic nerve cupping, optic nerve cup/disc ratio, or glaucomatous optic disc atrophy. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in optic nerve/papilla classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

25. Change From Baseline in Ophthalmologic Examination - Assessment of Optic Nerve and Papilla of the Left Eye [Baseline and Year 5]

    The optic nerve and papilla of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as optic nerve cupping, optic nerve cup/disc ratio, or glaucomatous optic disc atrophy. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in optic nerve/papilla classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

26. Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Blood Vessels of the Right Eye [Baseline and Year 5]

    The retinal blood vessels of the right eye were assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as retinal vascular disorder, retinopathy, and retinal hemorrhage. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal blood vessel classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

27. Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Blood Vessels of the Left Eye [Baseline and Year 5]

    The retinal blood vessels of the left eye were assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as retinal vascular disorder, retinopathy, and retinal hemorrhage. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal blood vessel classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

28. Change From Baseline in Ophthalmologic Examination - Assessment of Macula Lutea of the Right Eye [Baseline and Year 5]

    The macula lutea of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as maculopathy, retinal pigmentation, macular degeneration, diabetic retinopathy, retinal hemorrhage or aneurysm. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in macula lutea classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

29. Change From Baseline in Ophthalmologic Examination - Assessment of Macula Lutea of the Left Eye [Baseline and Year 5]

    The macula lutea of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as maculopathy, retinal pigmentation, macular degeneration, diabetic retinopathy, retinal hemorrhage or aneurysm. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in macula lutea classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Had Gastro Esophageal Reflux disease with or without oesophagitis.

• Had a history of heartburn at least for 5 days per week during the past 6 months or was receiving long-term treatment with a proton pump inhibitor and during two weeks (without proton pump inhibitor treatment) prior to enrolment.

Exclusion Criteria:

• History of surgery of stomach or oesophagus.

• Gastric ulcer (can be included after healing of gastric ulcer).

• Duodenal ulcer (can be included after healing of duodenal ulcer).

• Bleeding (melena, hematemesis).

• Severe concomitant disease (cancer, cardiovascular, renal, hepatic diseases).

• Barrett oesophagus with dysplasia.

• Complicated esophagitis (oesophageal strictures or ulcers).

• Treatment with proton pump inhibitor or Histamine receptor 2 (H2)antagonists within the previous two weeks.

• Pregnancy, wish to become pregnant, breast feeding.

• Treatment with non steroidal anti-inflammatory drugs, treatment with acetylsalicylic acid (aspirin) > 100 mg/day.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Takeda

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01135368
• Other Study ID Numbers: AGO K019; U1111-1115-1139
• First Posted: Jun 2, 2010
• Last Update Posted: Sep 3, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Takeda: GERD; Gastroesophageal Reflux Disease; Drug Therapy
• Additional relevant MeSH terms: Gastroesophageal Reflux; Lansoprazole; Dexlansoprazole

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 38 investigative sites in Germany from 18 June 2002 to 24 September 2008.
Pre-assignment Detail	Participants with a historical diagnosis of Gastro Esophageal Reflux disease (GERD) received treatment with Lansoprazole at the usual dosage.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Period Title: Overall Study
STARTED	506
COMPLETED	255
NOT COMPLETED	251

Baseline Characteristics

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Overall Participants	506
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.5 (12.1)
Sex: Female, Male (Count of Participants)
Female	218 43.1%
Male	288 56.9%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	502 99.2%
Black	2 0.4%
Oriental	2 0.4%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.1 (9.3)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82.2 (13.7)
Body Mass Index (BMI) (kg/cm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/cm^2]	28.09 (4.15)
Diagnosis of Reflux Disease (participants) [Number]
First diagnosis	150 29.6%
Recurrence	356 70.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Reflux Disease Symptom - Heartburn
Description	Heartburn symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	None	Mild	Moderate	Severe
Arm/Group Description	Participants with no symptoms at Baseline.	Participants with mild symptoms at Baseline.	Participants with moderate symptoms at Baseline.	Participants with severe symptoms at Baseline.
Measure Participants	0	69	156	257
Week 8 Symptoms: None	59 11.7%	117 NaN	186 NaN
Week 8 Symptoms: Mild	7 1.4%	27 NaN	43 NaN
Week 8 Symptoms: Moderate	0 0%	4 NaN	12 NaN
Week 8 Symptoms: Severe	0 0%	0 NaN	2 NaN
Week 8 Missing data	3 0.6%	8 NaN	14 NaN

2. Primary Outcome

Title	Change From Baseline in Reflux Disease Symptoms - Acid Regurgitation
Description	Acid regurgitation symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	None	Mild	Moderate	Severe
Arm/Group Description	Participants with no symptoms at Baseline.	Participants with mild symptoms at Baseline.	Participants with moderate symptoms at Baseline.	Participants with severe symptoms at Baseline.
Measure Participants	66	136	166	114
Week 8 Symptoms: None	58 11.5%	113 NaN	125 NaN	81 NaN
Week 8 Symptoms: Mild	4 0.8%	19 NaN	28 NaN	22 NaN
Week 8 Symptoms: Moderate	1 0.2%	0 NaN	2 NaN	3 NaN
Week 8 Symptoms: Severe	0 0%	0 NaN	1 NaN	0 NaN
Week 8 Missing data	3 0.6%	4 NaN	10 NaN	8 NaN

3. Primary Outcome

Title	Change From Baseline in Reflux Disease Symptom - Difficulty Swallowing
Description	Difficulty swallowing symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	None	Mild	Moderate	Severe
Arm/Group Description	Participants with no symptoms at Baseline.	Participants with mild symptoms at Baseline.	Participants with moderate symptoms at Baseline.	Participants with severe symptoms at Baseline.
Measure Participants	316	102	45	19
Week 8 Symptoms: None	293 57.9%	89 NaN	33 NaN	13 NaN
Week 8 Symptoms: Mild	7 1.4%	9 NaN	5 NaN	2 NaN
Week 8 Symptoms: Moderate	3 0.6%	0 NaN	1 NaN	1 NaN
Week 8 Symptoms: Severe	0 0%	0 NaN	1 NaN	1 NaN
Week 8 Missing data	13 2.6%	4 NaN	5 NaN	2 NaN

4. Primary Outcome

Title	Change From Baseline in Reflux Disease Symptom - Pain in Upper Abdomen
Description	Pain in the upper abdomen symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	None	Mild	Moderate	Severe
Arm/Group Description	Participants with no symptoms at Baseline.	Participants with mild symptoms at Baseline.	Participants with moderate symptoms at Baseline.	Participants with severe symptoms at Baseline.
Measure Participants	139	155	120	68
Week 8 Symptoms: None	124 24.5%	125 NaN	86 NaN	44 NaN
Week 8 Symptoms: Mild	9 1.8%	19 NaN	21 NaN	10 NaN
Week 8 Symptoms: Moderate	0 0%	4 NaN	2 NaN	8 NaN
Week 8 Symptoms: Severe	0 0%	0 NaN	1 NaN	3 NaN
Week 8 Missing data	6 1.2%	7 NaN	10 NaN	3 NaN

5. Primary Outcome

Title	Change From Baseline in Reflux Disease Symptom - Nausea & Vomiting
Description	Nausea and vomiting symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	None	Mild	Moderate	Severe
Arm/Group Description	Participants with no symptoms at Baseline.	Participants with mild symptoms at Baseline.	Participants with moderate symptoms at Baseline.	Participants with severe symptoms at Baseline.
Measure Participants	330	98	36	18
Week 8 Symptoms: None	303 59.9%	78 NaN	25 NaN	13 NaN
Week 8 Symptoms: Mild	10 2%	9 NaN	9 NaN	2 NaN
Week 8 Symptoms: Moderate	2 0.4%	1 NaN	2 NaN	2 NaN
Week 8 Symptoms: Severe	0 0%	0 NaN	0 NaN	0 NaN
Week 8 Missing data	15 3%	10 NaN	0 NaN	1 NaN

6. Primary Outcome

Title	Change From Baseline in Reflux Disease Symptom - Cough & Sore Throat
Description	Cough and sore throat symptoms were assessed by the Investigator at Baseline and the Week 8 visit. The shift table below summarizes the individual transitions in symptom intensity (mild, moderate, severe or none) between Baseline (depicted in the columns) and Week 8 (depicted in the rows) for all patients.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	None	Mild	Moderate	Severe
Arm/Group Description	Participants with no symptoms at Baseline.	Participants with mild symptoms at Baseline.	Participants with moderate symptoms at Baseline.	Participants with severe symptoms at Baseline.
Measure Participants	343	81	35	23
Week 8 Symptoms: None	305 60.3%	71 NaN	24 NaN	14 NaN
Week 8 Symptoms: Mild	16 3.2%	4 NaN	7 NaN	6 NaN
Week 8 Symptoms: Moderate	3 0.6%	3 NaN	0 NaN	2 NaN
Week 8 Symptoms: Severe	0 0%	0 NaN	0 NaN	0 NaN
Week 8 Missing data	19 3.8%	3 NaN	4 NaN	1 NaN

7. Primary Outcome

Title	Change From Baseline in Endoscopic Healing of Erosive Reflux Disease as Assessed by Endoscopy
Description	Los Angeles Classification is used to grade the extension of changes in the oesophagus induced by reflux disease (Grade 0: normal aspect of mucosa; Grade A: ≥1 mucosal breaks no longer than 5 mm; Grade B: ≥1 mucosal breaks >5 mm long; Grade C: mucosal breaks extending between tops of two or more mucosal folds but are <75% of the circumference; Grade D: mucosal breaks ≥75% of the circumference). Healed defined as anything less than Grade A criteria. The shift table below summarizes the individual transitions in Los Angeles classification between Baseline (table columns) and Week 8 (table rows).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent to treat population, including all patients who received at least one dose of study medication and had a subsequent rating of the primary efficacy variable.

Arm/Group Title	Grade 0	Grade A	Grade B	Grade C	Grade D
Arm/Group Description	Participants with Grade 0 (normal aspect of mucosa) at Baseline.	Participants with Grade A (one or more mucosal breaks no longer than 5 mm, none of which extends between the tops of the mucosal folds) at Baseline.	Participants with Grade B (one or more mucosal breaks more than 5 mm long, none of which extends between the tops of two mucosal folds) at Baseline.	Participants with Grade C (mucosal breaks that extend between the tops of two or more mucosal folds, but which involve less than 75% of the oesophageal circumference) at Baseline.	Participants with Grade D (mucosal breaks which involve at least 75% of the oesophageal circumference) at Baseline.
Measure Participants	168	149	118	39	8
Week 8: Grade 0	38 7.5%	97 NaN	79 NaN	17 NaN	4 NaN
Week 8: Grade A	0 0%	17 NaN	19 NaN	6 NaN	2 NaN
Week 8: Grade B	0 0%	0 NaN	3 NaN	1 NaN	1 NaN
Week 8: Grade C	0 0%	0 NaN	0 NaN	1 NaN	1 NaN
Week 8: No data	130 25.7%	35 NaN	17 NaN	14 NaN	0 NaN

8. Secondary Outcome

Title	Change From Baseline in Enterochromaffin-like Cell Hyperplasia
Description	Enterochromaffin-like (ECL) cells were evaluated and classified by histopathological examinations as Normal, Simple (diffuse) hyperplasia, or Linear, chain producing hyperplasia. The shift table below summarizes the individual transitions in ECL-cell classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows) for all patients.
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	Normal	Simple	Linear	No Data
Arm/Group Description	Participants with normal ECL cell classification at Baseline.	Participants with simple (diffuse) hyperplasia at Baseline.	Participants with linear, chain producing hyperplasia at Baseline.	Participants with no data at Baseline.
Measure Participants	446	13	1	46
Year 5: Normal	315 62.3%	8 NaN	1 NaN	26 NaN
Year 5: Simple hyperplasia	10 2%	2 NaN	0 NaN	4 NaN
Year 5: Linear hyperplasia	13 2.6%	0 NaN	0 NaN	2 NaN
Year 5: No data	108 21.3%	3 NaN	0 NaN	14 NaN

9. Secondary Outcome

Title	Change From Baseline in Antrum Atrophy
Description	Atrophy was assessed by histopathological examination of cells biopsied from the antrum and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in atrophy classification (mild, moderate, severe or none) between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	No Atrophy	Mild	Moderate	Severe	No Data
Arm/Group Description	Participants with no atrophy at Baseline.	Participants with mild atrophy at Baseline.	Participants with moderate atrophy at Baseline.	Participants with severe atrophy at Baseline.	Participants with no data at Baseline.
Measure Participants	408	57	7	1	33
Year 5: No atrophy	306 60.5%	23 NaN	4 NaN	1 NaN	23 NaN
Year 5: Mild atrophy	7 1.4%	1 NaN	1 NaN	0 NaN	2 NaN
Year 5: Moderate atrophy	4 0.8%	5 NaN	1 NaN	0 NaN	0 NaN
Year 5: Severe atrophy	0 0%	0 NaN	0 NaN	0 NaN	1 NaN
Year 5: No data	91 18%	28 NaN	1 NaN	0 NaN	7 NaN

10. Secondary Outcome

Title	Change From Baseline in Corpus Atrophy
Description	Atrophy was assessed by histopathological examination of cells biopsied from the corpus and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in atrophy classification (mild, moderate, severe or none) between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	No Atrophy	Mild	Moderate	Severe	No Data
Arm/Group Description	Participants with no atrophy at Baseline.	Participants with mild atrophy at Baseline.	Participants with moderate atrophy at Baseline.	Participants with severe atrophy at Baseline.	Participants with no data at Baseline.
Measure Participants	451	23	2	0	30
Year 5: No atrophy	330 65.2%	12 NaN	1 NaN	17 NaN
Year 5: Mild atrophy	9 1.8%	0 NaN	0 NaN	1 NaN
Year 5: Moderate atrophy	7 1.4%	2 NaN	1 NaN	0 NaN
Year 5: Severe atrophy	0 0%	1 NaN	0 NaN	1 NaN
Year 5: No data	105 20.8%	8 NaN	0 NaN	11 NaN

11. Secondary Outcome

Title	Change From Baseline in Average Antrum Chronic Inflammation Score
Description	Chronic inflammation of the antrum was assessed by histopathology and graded according to the Sydney classification: 0 = None; 1 = mild; 2 = moderate; 3 = Severe
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	506
Baseline (n=473)	0.8 (1.2)
Change from Baseline (n=353)	-0.2 (1.3)

12. Secondary Outcome

Title	Change From Baseline in Corpus Chronic Inflammation Score
Description	Chronic inflammation of the corpus was assessed by histopathology and graded according to the Sydney classification: 0 = None; 1 = mild; 2 = moderate; 3 = Severe.
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	506
Baseline (n=476)	0.4 (0.8)
Change from Baseline (n=363)	-0.0 (0.9)

13. Secondary Outcome

Title	Change From Baseline in Antrum Intestinal Metaplasia
Description	Intestinal metaplasia was assessed by biopsy and histopathological examination of the antrum and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in intestinal metaplasia classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	None	Mild	Moderate	Severe	No Data
Arm/Group Description	Participants with no intestinal metaplasia at Baseline.	Participants with mild intestinal metaplasia at Baseline.	Participants with moderate intestinal metaplasia at Baseline.	Participants with severe intestinal metaplasia at Baseline.	Participants with no intestinal metaplasia data at Baseline.
Measure Participants	438	28	7	0	33
Year 5: None	319 63%	13 NaN	4 NaN	23 NaN
Year 5: Mild	6 1.2%	2 NaN	2 NaN	2 NaN
Year 5: Moderate	5 1%	1 NaN	1 NaN	1 NaN
Year 5: Severe	0 0%	0 NaN	0 NaN	0 NaN
Year 5: No data	108 21.3%	12 NaN	0 NaN	7 NaN

14. Secondary Outcome

Title	Change From Baseline in Corpus Intestinal Metaplasia
Description	Intestinal metaplasia was assessed by biopsy and histopathological examination of the corpus and classified according to the Sydney classification as mild, moderate, severe or none. The shift table below summarizes the individual transitions in intestinal metaplasia classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	None	Mild	Moderate	Severe	No Data
Arm/Group Description	Participants with no intestinal metaplasia at Baseline.	Participants with mild intestinal metaplasia at Baseline.	Participants with moderate intestinal metaplasia at Baseline.	Participants with severe intestinal metaplasia at Baseline.	Participants with no intestinal metaplasia data at Baseline.
Measure Participants	472	4	0	0	30
Year 5: None	359 70.9%	1 NaN	18 NaN
Year 5: Mild	1 0.2%	2 NaN	0 NaN
Year 5: Moderate	0 0%	0 NaN	1 NaN
Year 5: Severe	0 0%	0 NaN	0 NaN
Year 5: No data	112 22.1%	1 NaN	11 NaN

15. Secondary Outcome

Title	Change From Baseline in Blood Analysis - Testosterone
Description	The change between testosterone measured at year 5 in males including final visit and Testosterone measured at baseline.
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all male participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	285
Baseline (n=285)	4.57 (1.566)
Change from Baseline (n=214)	0.16 (1.275)

16. Secondary Outcome

Title	Change From Baseline in Blood Analysis - Luteinizing Hormone
Description	The change between luteinizing hormone measured at year 5 in males including final visit and luteinizing hormone measured at baseline.
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all male participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	286
Baseline (n=286)	4.73 (3.183)
Change from Baseline (n=214)	0.71 (3.101)

17. Secondary Outcome

Title	Change From Baseline in Blood Analysis - Follicle Stimulating Hormone
Description	The change between follicle stimulating hormone (FSH) measured at year 5 in males including final visit and follicle stimulating hormone measured at baseline.
Time Frame	Baseline and Year 5.

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all male participants who received any study medication. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	286
Baseline (n=286)	7.62 (7.864)
Change from Baseline (n=214)	0.39 (4.714)

18. Secondary Outcome

Title	Ophthalmologic Examination - Visual Acuity
Description	Visual Acuity was measured using the Snellen eye chart at a distance of 6 meters. Acuity is expressed as a ratio of the test distance (6 M) / the distance the average eye can see the letters on a certain line of the eye chart. Visual acuity of 1 is normal; an individual with acuity of 0.5 could only recognize an object at half the distance compared to an individual with normal acuity.
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	506
Right Eye: Acuity at Baseline (n=443)	0.927 (0.174)
Right Eye: Acuity at Year 5 (n=376)	0.904 (0.186)
Left Eye: Acuity at Baseline (n=447)	0.919 (0.181)
Left Eye: Acuity at Year 5 (n=379)	0.894 (0.205)

19. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Adaptation Without Glare
Description	Adaptation is the ability of the eye to adjust to various levels of darkness and light. Normal and pathological status of adaptation without glare was defined as follows: Normal status: Contrast between 1:0.05 and 1:23.5. Pathological status: Contrast = 0 or contrast > 1:23.5. The shift table below summarizes the individual transitions in the classification of adaptation without glare between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	Missing Data	Decreased Due to Age	Pathological	Normal
Arm/Group Description	Participants with no data at Baseline.	Participants with adaptation decreased due to age at Baseline.	Participants with adaptation classified as pathological at Baseline.	Participants with adaptation classified as normal at Baseline.
Measure Participants	93	7	30	376
Year 5: Missing data	62 12.3%	1 NaN	4 NaN	73 NaN
Year 5: Decreased due to age	0 0%	4 NaN	0 NaN	1 NaN
Year 5: Pathological	1 0.2%	0 NaN	10 NaN	14 NaN
Year 5: Normal	30 5.9%	2 NaN	16 NaN	288 NaN

20. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Adaptation With Glare
Description	Adaptation is the ability of the eye to adjust to various levels of darkness and light. Normal and pathological status of adaptation with glare was defined as follows: Normal status: Contrast between 1:0.05 and 1:23.5. Pathological status: Contrast = 0 or contrast > 1:23.5. The shift table below summarizes the individual transitions in the classification of adaptation with glare between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	Missing Data	Decreased Due to Age	Pathological	Normal
Arm/Group Description	Participants with no data at Baseline.	Participants with adaptation decreased due to age at Baseline.	Participants with adaptation classified as pathological at Baseline.	Participants with adaptation classified as normal at Baseline.
Measure Participants	118	8	52	328
Year 5: Missing data	75 14.8%	2 NaN	12 NaN	58 NaN
Year 5: Decreased due to age	2 0.4%	4 NaN	0 NaN	1 NaN
Year 5: Pathological	8 1.6%	0 NaN	16 NaN	18 NaN
Year 5: Normal	33 6.5%	2 NaN	24 NaN	251 NaN

21. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Accommodation
Description	Accommodation is the adjustment of the focal length of the eye lens to keep an object in focus on the retina as its distance from the eye varies, and is measured in diopters: Diopters = 1/(focal length).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis where data were available. Last observation carried forward was utilized.

Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
Measure Participants	506
Right Eye: Baseline (n=424)	2.877 (2.884)
Right Eye: Change from Baseline (n=348)	-0.090 (2.634)
Left Eye: Baseline (n=426)	2.835 (2.831)
Left Eye: Change from Baseline (n=349)	-0.073 (2.585)

22. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Color Vision
Description	Color vision was assessed by an Ophthalmologist and classified as normal or pathological. Pathological findings include abnormal color vision tests, color blindness and anomalous quotient. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in color vision classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no color vision data at Baseline.	Participants with normal color vision at Baseline.	Participants with pathological color vision at Baseline.
Measure Participants	58	406	42
Year 5: No data	46 9.1%	76 NaN	5 NaN
Year 5: Normal	12 2.4%	320 NaN	10 NaN
Year 5: Pathological	0 0%	10 NaN	27 NaN

23. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Cornea Assessment of Right Eye
Description	The cornea of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, corneal degeneration, opacity, scars or deposits. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in corneal classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	425	24
Year 5: No data	46 9.1%	78 NaN	3 NaN
Year 5: Normal	11 2.2%	343 NaN	5 NaN
Year 5: Pathological	0 0%	4 NaN	16 NaN

24. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Cornea Assessment of Left Eye
Description	The cornea of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, corneal degeneration, opacity, scars or deposits. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in corneal classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	429	20
Year 5: No data	46 9.1%	77 NaN	4 NaN
Year 5: Normal	11 2.2%	348 NaN	5 NaN
Year 5: Pathological	0 0%	4 NaN	11 NaN

25. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Lens Assessment of Right Eye
Description	The lens of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, lenticular opacities, vacuoles or pseudophakia. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in lens classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	293	156
Year 5: No data	46 9.1%	56 NaN	25 NaN
Year 5: Normal	8 1.6%	193 NaN	7 NaN
Year 5: Pathological	3 0.6%	44 NaN	124 NaN

26. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Lens Assessment of Left Eye
Description	The lens of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as cataracts, lenticular opacities, vacuoles or pseudophakia. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in lens classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	292	157
Year 5: No data	46 9.1%	56 NaN	25 NaN
Year 5: Normal	6 1.2%	193 NaN	8 NaN
Year 5: Pathological	5 1%	43 NaN	124 NaN

27. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Vitreous Body Assessment of Right Eye
Description	The vitreous body of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as myodesopsia, vitreous opacities, degeneration, detachment or prolapse. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in vitreous body classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	422	27
Year 5: No data	46 9.1%	73 NaN	8 NaN
Year 5: Normal	11 2.2%	338 NaN	2 NaN
Year 5: Pathological	0 0%	11 NaN	17 NaN

28. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Vitreous Body Assessment of Left Eye
Description	The vitreous body of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as myodesopsia, vitreous opacities, degeneration, detachment or prolapse. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in vitreous body classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	59	421	26
Year 5: No data	47 9.3%	73 NaN	7 NaN
Year 5: Normal	12 2.4%	341 NaN	3 NaN
Year 5: Pathological	0 0%	7 NaN	16 NaN

29. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Aspect of the Right Eye
Description	The retinal aspect of the right eye (such as color anomalies) was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as deep red ocular fundus, fundus myopicus, retinal disorders, exudates or pigmentation. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal aspect classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	59	438	9
Year 5: No data	48 9.5%	80 NaN	0 NaN
Year 5: Normal	11 2.2%	356 NaN	1 NaN
Year 5: Pathological	0 0%	2 NaN	8 NaN

30. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Aspect of the Left Eye
Description	The retinal aspect of the left eye (such as color anomalies) was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as deep red ocular fundus, fundus myopicus, retinal disorders, exudates or pigmentation. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal aspect classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	442	7
Year 5: No data	46 9.1%	80 NaN	1 NaN
Year 5: Normal	11 2.2%	361 NaN	1 NaN
Year 5: Pathological	0 0%	1 NaN	5 NaN

31. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Optic Nerve and Papilla of the Right Eye
Description	The optic nerve and papilla of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as optic nerve cupping, optic nerve cup/disc ratio, or glaucomatous optic disc atrophy. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in optic nerve/papilla classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	59	422	25
Year 5: No data	48 9.5%	76 NaN	4 NaN
Year 5: Normal	11 2.2%	337 NaN	4 NaN
Year 5: Pathological	0 0%	9 NaN	17 NaN

32. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Optic Nerve and Papilla of the Left Eye
Description	The optic nerve and papilla of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as optic nerve cupping, optic nerve cup/disc ratio, or glaucomatous optic disc atrophy. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in optic nerve/papilla classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	422	27
Year 5: No data	46 9.1%	75 NaN	6 NaN
Year 5: Normal	11 2.2%	339 NaN	4 NaN
Year 5: Pathological	0 0%	8 NaN	17 NaN

33. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Blood Vessels of the Right Eye
Description	The retinal blood vessels of the right eye were assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as retinal vascular disorder, retinopathy, and retinal hemorrhage. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal blood vessel classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	59	369	78
Year 5: No data	48 9.5%	68 NaN	12 NaN
Year 5: Normal	7 1.4%	279 NaN	6 NaN
Year 5: Pathological	4 0.8%	22 NaN	60 NaN

34. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Retinal Blood Vessels of the Left Eye
Description	The retinal blood vessels of the left eye were assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as retinal vascular disorder, retinopathy, and retinal hemorrhage. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in retinal blood vessel classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	369	80
Year 5: No data	46 9.1%	68 NaN	13 NaN
Year 5: Normal	7 1.4%	278 NaN	7 NaN
Year 5: Pathological	4 0.8%	23 NaN	60 NaN

35. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Macula Lutea of the Right Eye
Description	The macula lutea of the right eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as maculopathy, retinal pigmentation, macular degeneration, diabetic retinopathy, retinal hemorrhage or aneurysm. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in macula lutea classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	60	412	34
Year 5: No data	49 9.7%	75 NaN	4 NaN
Year 5: Normal	10 2%	317 NaN	3 NaN
Year 5: Pathological	1 0.2%	20 NaN	27 NaN

36. Secondary Outcome

Title	Change From Baseline in Ophthalmologic Examination - Assessment of Macula Lutea of the Left Eye
Description	The macula lutea of the left eye was assessed by an Ophthalmologist and judged to be normal or pathological at Baseline and at Year 5. Pathological classification includes abnormal findings such as maculopathy, retinal pigmentation, macular degeneration, diabetic retinopathy, retinal hemorrhage or aneurysm. Normal indicates no pathological findings were observed. The shift table below summarizes the individual transitions in macula lutea classification between Baseline (depicted in the columns) and Year 5 (depicted in the rows).
Time Frame	Baseline and Year 5

Outcome Measure Data

Analysis Population Description

Safety analysis set, where data were available. Last observation carried forward was utilized.

Arm/Group Title	No Data	Normal	Pathological
Arm/Group Description	Participants with no data at Baseline.	Participants with normal assessment at Baseline.	Participants with pathological assessment at Baseline.
Measure Participants	57	418	31
Year 5: No data	46 9.1%	77 NaN	4 NaN
Year 5: Normal	10 2%	323 NaN	5 NaN
Year 5: Pathological	1 0.2%	18 NaN	22 NaN

Adverse Events

Time Frame	Starting with the first administration of study medication for up to 14 days after last dose of study medication.
Adverse Event Reporting Description	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.
Arm/Group Title	Lansoprazole
Arm/Group Description	Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks. Depending on response, dosage could then be decreased to 15 mg, once daily, or increased to 30 mg, twice daily for up to 4 years and 10 months.
All Cause Mortality
	Lansoprazole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lansoprazole
	Affected / at Risk (%)	# Events
Total	82/506 (16.2%)
Cardiac disorders
Coronary artery disease	4/506 (0.8%)
Myocardial infarction	3/506 (0.6%)
Atrial flutter	1/506 (0.2%)
Angina pectoris	1/506 (0.2%)
Acute coronary syndrome	1/506 (0.2%)
Aortic valve stenosis	1/506 (0.2%)
Atrioventricular block complete	1/506 (0.2%)
Pleuropericarditis	1/506 (0.2%)
Ear and labyrinth disorders
Sudden hearing loss	1/506 (0.2%)
Vertigo	1/506 (0.2%)
Vertigo positional	1/506 (0.2%)
Eye disorders
Diplopia	1/506 (0.2%)
Gastrointestinal disorders
Abdominal discomfort	1/506 (0.2%)
Abdominal pain upper	1/506 (0.2%)
Colonic polyp	1/506 (0.2%)
Crohn's disease	1/506 (0.2%)
Diarrhoea	1/506 (0.2%)
Gastrointestinal haemorrhage	1/506 (0.2%)
Haematochezia	1/506 (0.2%)
Ileus	1/506 (0.2%)
Nausea	1/506 (0.2%)
Rectal haemorrhage	1/506 (0.2%)
Rectocele	1/506 (0.2%)
General disorders
Chest pain	1/506 (0.2%)
Impaired healing	1/506 (0.2%)
Sudden death	1/506 (0.2%)
Hepatobiliary disorders
Biliary colic	2/506 (0.4%)
Cholecystitis	1/506 (0.2%)
Cholelithiasis	1/506 (0.2%)
Jaundice cholestatic	1/506 (0.2%)
Infections and infestations
Bronchopneumonia	1/506 (0.2%)
Neuroborreliosis	1/506 (0.2%)
Papilloma viral infection	1/506 (0.2%)
Pneumonia	1/506 (0.2%)
Vulval abscess	1/506 (0.2%)
Injury, poisoning and procedural complications
Ligament rupture	2/506 (0.4%)
Concussion	1/506 (0.2%)
Contusion	1/506 (0.2%)
Excoriation	1/506 (0.2%)
Facial bones fracture	1/506 (0.2%)
Fall	1/506 (0.2%)
Hand fracture	1/506 (0.2%)
Humerus fracture	1/506 (0.2%)
Lower limb fracture	1/506 (0.2%)
Meniscus lesion	1/506 (0.2%)
Post procedural haematoma	1/506 (0.2%)
Radius fracture	1/506 (0.2%)
Metabolism and nutrition disorders
Diabetes mellitus	1/506 (0.2%)
Hypoglycaemia	1/506 (0.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	3/506 (0.6%)
Intervertebral disc protrusion	2/506 (0.4%)
Lumbar spinal stenosis	1/506 (0.2%)
Neck pain	1/506 (0.2%)
Pain in extremity	1/506 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma	2/506 (0.4%)
Rectal cancer	2/506 (0.4%)
Uterine leiomyoma	2/506 (0.4%)
Astrocytoma	1/506 (0.2%)
Bladder cancer recurrent	1/506 (0.2%)
Breast cancer female	1/506 (0.2%)
Diffuse large B-cell lymphoma	1/506 (0.2%)
Gastrointestinal stromal tumour	1/506 (0.2%)
Hepatic neoplasm	1/506 (0.2%)
Hypopharyngeal cancer	1/506 (0.2%)
Metastatic bronchial carcinoma	1/506 (0.2%)
Nasopharyngeal cancer	1/506 (0.2%)
Oesophageal squamous cell carcinoma	1/506 (0.2%)
Ovarian cancer	1/506 (0.2%)
Prostate cancer	1/506 (0.2%)
Renal oncocytoma	1/506 (0.2%)
Seminoma	1/506 (0.2%)
Uterine cancer	1/506 (0.2%)
Nervous system disorders
Cerebrovascular accident	4/506 (0.8%)
Carpal tunnel syndrome	1/506 (0.2%)
Restless leg syndrome	1/506 (0.2%)
Brain stem infarction	1/506 (0.2%)
Carotid sinus syndrome	1/506 (0.2%)
Cerebellar infarction	1/506 (0.2%)
Cerebral haemorrhage	1/506 (0.2%)
Convulsion	1/506 (0.2%)
Dizziness	1/506 (0.2%)
Paresis cranial nerve	1/506 (0.2%)
Sciatica	1/506 (0.2%)
Psychiatric disorders
Depression	4/506 (0.8%)
Anxiety disorder	1/506 (0.2%)
Completed suicide	1/506 (0.2%)
Generalised anxiety disorder	1/506 (0.2%)
Panic attack	1/506 (0.2%)
Panic disorder	1/506 (0.2%)
Renal and urinary disorders
Incontinence	1/506 (0.2%)
Renal colic	1/506 (0.2%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/506 (0.2%)
Menorrhagia	1/506 (0.2%)
Prostatitis	1/506 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	2/506 (0.4%)
Haemoptysis	1/506 (0.2%)
Hyperventilation	1/506 (0.2%)
Surgical and medical procedures
Toe operation	1/506 (0.2%)
Vascular disorders
Varicose vein	2/506 (0.4%)
Hypertension	1/506 (0.2%)
Subclavian artery stenosis	1/506 (0.2%)
Thrombosis	1/506 (0.2%)
Vascular pseudoaneurysm	1/506 (0.2%)
Other (Not Including Serious) Adverse Events
	Lansoprazole
	Affected / at Risk (%)	# Events
Total	114/506 (22.5%)
Gastrointestinal disorders
Diarrhoea	28/506 (5.5%)
Infections and infestations
Bronchitis	46/506 (9.1%)
Musculoskeletal and connective tissue disorders
Back pain	29/506 (5.7%)
Vascular disorders
Hypertension	30/506 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.