RELAX: Safety and Efficacy Study to Determine Anti-Asthmatic Effect of Esomeprazole Magnesium; Nexium Reflux Asthma

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00317044
• Collaborator: (none)
• Enrollment: 961
• Locations: 134
• Arms: 3
• Duration (Months): 27
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether treatment with esomeprazole for 6 months will improve asthma in adult patients with moderate to severe asthma and symptoms of gastroesophageal reflux disease.

Condition or Disease	Intervention/Treatment	Phase
Asthma; GERD	Drug: Esomeprazole; Drug: Esomeprazole; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 961 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 6-month Randomized, Double-blind, Parallel-group, Multicentre, Placebo-controlled Phase II Study to Compare Anti-asthmatic Effect and Safety of Esomeprazole (Nexium®) 40 mg Twice Daily or 40 mg Once Daily With Placebo in Adults With Asthma
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Esomeprazole 40 mg twice daily	Drug: Esomeprazole; Esomeprazole 40 mg twice daily
Experimental: Esomeprazole 40 mg once daily	Drug: Esomeprazole; Esomeprazole 40 mg once daily
Placebo Comparator: Placebo	Drug: Placebo; Placebo twice daily

Outcome Measures

Primary Outcome Measures

1. Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period). [Baseline to 6 months]

   Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. Results presented as a mean of all available data during the treatment period.

Secondary Outcome Measures

1. Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute)) [Baseline to 6 months]

   Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. No dispersion measure available.

2. Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total [Baseline to 6 months]

   Participants must have both baseline and flow up measure to be included in analysis. Each morning and evening, the patient will be asked to record his/her asthma symptoms (sx) in the diary. The asthma sx scores during night- and daytime will be assessed by the patient according to the following scoring system: 0 = no asthma sx; 1 = you are aware of your asthma sx but can easily tolerate the sx; 2 = your asthma sx are causing you enough discomfort to cause problems with normal activities (or with sleep); 3 = you are unable to do your normal activities (or sleep) because of your asthma. The total symptom score is the sum of the night- and daytime scores.

3. Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months [Baseline to 6 months]

   This is the change in the average number of inhalations from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. Treatment mean calculated using the entire treatment period.

4. Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma [Baseline to 6 months]

   Change in percentage of nights with night-time awakening(s) due to asthma from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis.

5. Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period. [From randomization (Visit 3) to visit 7.]

   Description: Changes in forced expiratory volume in 1 second (FEV1) from randomization (Visit 3) to the treatment period considered as mean value at Visits 4-7. Participants must have both baseline and follow up measure to be included in analysis.

6. Number of Patients With Severe Asthma Exacerbations. [Up to 6 months]

7. Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7 [From randomization (Visit 3) to Visit 7]

   The Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S))has been developed by and includes 32 questions in 4 domains: activity limitation, symptoms, emotional function, and exposure to environmental stimuli. It is used to measure the physical and emotional impact of the disease in the selected areas of life. Participants must have both baseline and follow up measure to be included in analysis.AQLQ(S) score based on a 7-point scale that ranged from 1 (worst quality of life) to 7 (best quality of life).

8. Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7 [Randomization (Visit 3) to Visit 7]

   The RDQ questionnaire is used to assess six GI symptoms during the previous week (a burning feeling behind the breastbone, pain behind the breastbone, a burning feeling in the centre of the stomach, pain in the centre of the stomach, an acid taste in the mouth, unpleasant movement of material upwards from the stomach). Each symptom is given a frequency score on a six-point scale (from 0=did not have to 5=daily) and an intensity score on a six-point scale (from 0=did not have to 5=severe). Three domain scores are calculated by forming averages of the frequency and intensity scores of selected symptoms (heartburn: the first two symptoms; dyspepsia: the next two symptoms; regurgitation: the last two symptoms). The overall GERD score is calculated as the average of the hearburn and dyspepsia domain scores. The GERD score can thus range from 0 to 5.

9. Number of Severe Adverse Events [Up to 6 months]

10. Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night [Baseline to 6 months]

    Participants must have both baseline and follow up measure to be included in analysis

11. Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day [Baseline to 6 months]

    Participants must have both baseline and follow up measure to be included in analysis

12. Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night [Baseline to 6 months]

    Participants must have both baseline and follow up measure to be included in analysis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults with diagnosis of asthma since at least 6 months.

• Symptoms of asthma during run-in.

• At least 3 months history and present symptoms of 1 or more of the following: burning feeling behind breastbone, pain behind breastbone, acid taste in the mouth.

Exclusion Criteria:

• Patients with clinically relevant abnormalities.

• Patients with a smoking history of ≥10 pack-year.

• Patients who have had previous surgery on the esophagus or the stomach.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Scottsdale	Arizona	United States
3	Research Site	Little Rock	Arkansas	United States
4	Research Site	Fountain Valley	California	United States
5	Research Site	Miami	Florida	United States
6	Research Site	Atlanta	Georgia	United States
7	Research Site	Stockbridge	Georgia	United States
8	Research Site	Normal	Illinois	United States
9	Research Site	Overland Park	Kansas	United States
10	Research Site	Wichita	Kansas	United States
11	Research Site	Mandeville	Louisiana	United States
12	Research Site	Wheaton	Maryland	United States
13	Research Site	St. Louis	Missouri	United States
14	Research Site	Papillion	Nebraska	United States
15	Research Site	Asheville	North Carolina	United States
16	Research Site	Cincinnati	Ohio	United States
17	Research Site	Sylvania	Ohio	United States
18	Research Site	Medford	Oregon	United States
19	Research Site	Pittsburgh	Pennsylvania	United States
20	Research Site	Upland	Pennsylvania	United States
21	Research Site	Charleston	South Carolina	United States
22	Research Site	Austin	Texas	United States
23	Research Site	Houston	Texas	United States
24	Research Site	San Antonio	Texas	United States
25	Research Site	Kirkland	Washington	United States
26	Research Site	Seattle	Washington	United States
27	Research Site	Greenfield	Wisconsin	United States
28	Research Site	Monte Grande	Buenos Aires	Argentina
29	Research Site	Quilmes	Buenos Aires	Argentina
30	Research Site	Córdoba	Córdoba, Argentina	Argentina
31	Research Site	Rosario	Santa Fe, Argentina	Argentina
32	Research Site	Rosario	Santa Fe	Argentina
33	Research Site	San Miguel De Tucumán	Tucumán, Argentina	Argentina
34	Research Site	Buenos Aires		Argentina
35	Research Site	Ciudad Autónoma de Buenos Aires		Argentina
36	Research Site	Ciudad de Buenos Aires		Argentina
37	Research Site	Córdoba		Argentina
38	Research Site	Pleven		Bulgaria
39	Research Site	Plovdiv		Bulgaria
40	Research Site	Russe		Bulgaria
41	Research Site	Sofia		Bulgaria
42	Research Site	Varna		Bulgaria
43	Research Site	Calgary	Alberta	Canada
44	Research Site	Bay Roberts	Newfoundland and Labrador	Canada
45	Research Site	Holyrood	Newfoundland and Labrador	Canada
46	Research Site	Brampton	Ontario	Canada
47	Research Site	Hamilton	Ontario	Canada
48	Research Site	Mississauga	Ontario	Canada
49	Research Site	Toronto	Ontario	Canada
50	Research Site	Woodstock	Ontario	Canada
51	Research Site	La Malbaie	Quebec	Canada
52	Research Site	Montreal	Quebec	Canada
53	Research Site	Quebec		Canada
54	Research Site	Benesov U Prahy		Czech Republic
55	Research Site	Beroun		Czech Republic
56	Research Site	Cvikov		Czech Republic
57	Research Site	Kladno		Czech Republic
58	Research Site	Kolin 4		Czech Republic
59	Research Site	Liberec		Czech Republic
60	Research Site	Praha 10		Czech Republic
61	Research Site	Praha 4		Czech Republic
62	Research Site	Praha 6		Czech Republic
63	Research Site	Rokycany		Czech Republic
64	Research Site	Tabor		Czech Republic
65	Research Site	Brest		France
66	Research Site	Ferolles Attilly		France
67	Research Site	Grasse		France
68	Research Site	Grenoble		France
69	Research Site	Marseille Cedex 06		France
70	Research Site	Montpellier		France
71	Research Site	Paris Cedex		France
72	Research Site	St Laurent Du Var		France
73	Research Site	Villejuif		France
74	Research Site	Bad Wörishofen		Germany
75	Research Site	Berlin		Germany
76	Research Site	Frankfurt		Germany
77	Research Site	Freising		Germany
78	Research Site	Gelnhausen		Germany
79	Research Site	Gelsenkirchen		Germany
80	Research Site	Hamburg		Germany
81	Research Site	Landsberg		Germany
82	Research Site	Marburg		Germany
83	Research Site	Nürnberg		Germany
84	Research Site	Potsdam		Germany
85	Research Site	Rodgau-dudenhofen		Germany
86	Research Site	Wolmirstedt		Germany
87	Research Site	Budapest		Hungary
88	Research Site	Füzesabony		Hungary
89	Research Site	Gyöngyös		Hungary
90	Research Site	Győr		Hungary
91	Research Site	Hódmezővásárhely		Hungary
92	Research Site	Kaposvár		Hungary
93	Research Site	Mosonmagyaróvár		Hungary
94	Research Site	Szombathely		Hungary
95	Research Site	Százhalombatta		Hungary
96	Research Site	Cagliari	CA	Italy
97	Research Site	Crema	CR	Italy
98	Research Site	Firenze	FI	Italy
99	Research Site	Arenzano	GE	Italy
100	Research Site	Palermo	PA	Italy
101	Research Site	Pisa	PI	Italy
102	Research Site	Prato	PO	Italy
103	Research Site	Bussolengo	VR	Italy
104	Research Site	Verona	VR	Italy
105	Research Site	Napoli		Italy
106	Research Site	Roma		Italy
107	Research Site	Guadalajara	Jalisco	Mexico
108	Research Site	Zapopan	Jalisco	Mexico
109	Research Site	Morelia	Michoacan	Mexico
110	Research Site	Villahermosa	Tabasco	Mexico
111	Research Site	Mexico		Mexico
112	Research Site	Bydgoszcz		Poland
113	Research Site	Gdynia		Poland
114	Research Site	Iława		Poland
115	Research Site	Kraków		Poland
116	Research Site	Piekary Śląskie		Poland
117	Research Site	Skarżysko-Kamienna		Poland
118	Research Site	Strzelce Opolskie		Poland
119	Research Site	Tarnów		Poland
120	Research Site	Zabrze		Poland
121	Research Site	Łódź		Poland
122	Research Site	Amadora		Portugal
123	Research Site	Covilhã		Portugal
124	Research Site	Porto		Portugal
125	Research Site	Vila Nova de Gaia		Portugal
126	Research Site	Bratislava		Slovakia
127	Research Site	Kosice		Slovakia
128	Research Site	Nove Zamky		Slovakia
129	Research Site	Nové Zámky		Slovakia
130	Research Site	Povazska Bystrica		Slovakia
131	Research Site	Prievidza		Slovakia
132	Research Site	Rimavska Sobota		Slovakia
133	Research Site	Trenčín		Slovakia
134	Research Site	Basel	Basel Stadt	Switzerland

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: AstraZeneca Nexium Medical Science Director, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR-D9618C00001.pdf

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00317044
• Other Study ID Numbers: D9618C00001; RELAX
• First Posted: Apr 24, 2006
• Last Update Posted: Jun 9, 2014
• Last Verified: May 1, 2014

• Keywords provided by AstraZeneca: Moderate to severe Asthma; Gastroesophageal Reflux Disease; esomeprazole; GERD
• Additional relevant MeSH terms: Asthma; Esomeprazole

Study Results

Participant Flow

Pre-assignment Detail	Four randomized patients were excluded from the ITT analysis due to missing efficacy data (2 patients), no investigational product given (1 patient), and being unblinded by the investigator (1 patient). The patient who received no investigational product was excluded from the safety analysis and is not included in the Baseline Characteristics.

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Period Title: Overall Study
STARTED	320	313	328
COMPLETED	272	273	283
NOT COMPLETED	48	40	45

Baseline Characteristics

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo	Total
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo	Total of all reporting groups
Overall Participants	319	313	328	960
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	44.0	45.0	45.0	44.667
Sex: Female, Male (Count of Participants)
Female	240.00 75.2%	240.00 76.7%	247.00 75.3%	727 75.7%
Male	79.00 24.8%	73.00 23.3%	81.00 24.7%	233 24.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Morning Peak Expiratory Flow (mPEF (L/Minute)) From Baseline (Mean of the Last 7 Days in the run-in Period) to Treatment Period (Mean of All Available Data During the Treatment Period).
Description	Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. Results presented as a mean of all available data during the treatment period.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Least Squares Mean (Standard Error) [L/minute]	21.1891 (2.8689)	19.1847 (2.8422)	15.6771 (2.8086)

2. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute))
Description	Peak expiratory flow is defined as the maximum speed of expiration as measured with the Mini-Wright® PEF Meter. Participants must have both baseline and follow up measure to be included in analysis. No dispersion measure available.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	326
Least Squares Mean (Standard Error) [L/minute]	21.88 (2.89)	18.37 (2.87)	18.55 (2.83)

3. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total
Description	Participants must have both baseline and flow up measure to be included in analysis. Each morning and evening, the patient will be asked to record his/her asthma symptoms (sx) in the diary. The asthma sx scores during night- and daytime will be assessed by the patient according to the following scoring system: 0 = no asthma sx; 1 = you are aware of your asthma sx but can easily tolerate the sx; 2 = your asthma sx are causing you enough discomfort to cause problems with normal activities (or with sleep); 3 = you are unable to do your normal activities (or sleep) because of your asthma. The total symptom score is the sum of the night- and daytime scores.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	315	311	326
Least Squares Mean (Standard Error) [Scores on a scale]	-0.61 (0.05721)	-0.47 (0.05652)	-0.52 (0.05609)

4. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Total From Baseline to 6 Months
Description	This is the change in the average number of inhalations from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis. Treatment mean calculated using the entire treatment period.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	315	311	326
Least Squares Mean (Standard Error) [Inhalations]	-0.77 (0.10)	-0.73 (0.10)	-0.68 (0.10)

5. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma
Description	Change in percentage of nights with night-time awakening(s) due to asthma from baseline to the end of the study (6 months). Participants must have both baseline and follow up measure to be included in analysis.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Least Squares Mean (Standard Error) [Percent of nights]	-0.238 (0.018)	-0.219 (0.018)	-0.223 (0.018)

6. Secondary Outcome

Title	Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period.
Description	Description: Changes in forced expiratory volume in 1 second (FEV1) from randomization (Visit 3) to the treatment period considered as mean value at Visits 4-7. Participants must have both baseline and follow up measure to be included in analysis.
Time Frame	From randomization (Visit 3) to visit 7.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	312	306	324
Least Squares Mean (Standard Error) [Liters]	0.09 (0.02)	0.07 (0.02)	0.02 (0.02)

7. Secondary Outcome

Title	Number of Patients With Severe Asthma Exacerbations.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	318	312	327
Number [Participants]	33 10.3%	41 13.1%	43 13.1%

8. Secondary Outcome

Title	Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7
Description	The Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S))has been developed by and includes 32 questions in 4 domains: activity limitation, symptoms, emotional function, and exposure to environmental stimuli. It is used to measure the physical and emotional impact of the disease in the selected areas of life. Participants must have both baseline and follow up measure to be included in analysis.AQLQ(S) score based on a 7-point scale that ranged from 1 (worst quality of life) to 7 (best quality of life).
Time Frame	From randomization (Visit 3) to Visit 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	272	275	288
Least Squares Mean (Standard Error) [Scores on a scale]	0.97 (0.07)	0.83 (0.07)	0.55 (0.07)

9. Secondary Outcome

Title	Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7
Description	The RDQ questionnaire is used to assess six GI symptoms during the previous week (a burning feeling behind the breastbone, pain behind the breastbone, a burning feeling in the centre of the stomach, pain in the centre of the stomach, an acid taste in the mouth, unpleasant movement of material upwards from the stomach). Each symptom is given a frequency score on a six-point scale (from 0=did not have to 5=daily) and an intensity score on a six-point scale (from 0=did not have to 5=severe). Three domain scores are calculated by forming averages of the frequency and intensity scores of selected symptoms (heartburn: the first two symptoms; dyspepsia: the next two symptoms; regurgitation: the last two symptoms). The overall GERD score is calculated as the average of the hearburn and dyspepsia domain scores. The GERD score can thus range from 0 to 5.
Time Frame	Randomization (Visit 3) to Visit 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Least Squares Mean (Standard Error) [Scores on a scale]	-1.95 (0.07)	-1.91 (0.07)	-1.27 (0.07)

10. Secondary Outcome

Title	Number of Severe Adverse Events
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Number [Events]	4	5	9

11. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night
Description	Participants must have both baseline and follow up measure to be included in analysis
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Least Squares Mean (Standard Error) [Scores on a scale]	-0.31 (0.03)	-0.23 (0.03)	-0.27 (0.03)

12. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day
Description	Participants must have both baseline and follow up measure to be included in analysis
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Least Squares Mean (Standard Error) [Scores on a scale]	-0.30 (0.03)	-0.25 (0.03)	-0.25 (0.03)

13. Secondary Outcome

Title	Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night
Description	Participants must have both baseline and follow up measure to be included in analysis
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole 40 mg Twice Daily	Esomeprazole 40 mg Once Daily	Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily	Placebo
Measure Participants	316	311	327
Least Squares Mean (Standard Error) [Inhalations]	-0.30 (0.05)	-0.27 (0.05)	-0.29 (0.04)

Adverse Events

Arm/Group Title	Esomeprazole 40 mg Twice Daily		Esomeprazole 40 mg Once Daily		Placebo
Arm/Group Description	Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily		Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily		Placebo
All Cause Mortality
	Esomeprazole 40 mg Twice Daily		Esomeprazole 40 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Esomeprazole 40 mg Twice Daily		Esomeprazole 40 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/319 (2.2%)		5/313 (1.6%)		5/328 (1.5%)
Gastrointestinal disorders
Abdominal Pain	0/319 (0%)		0/313 (0%)		1/328 (0.3%)
Umbilical Hernia	0/319 (0%)		1/313 (0.3%)		0/328 (0%)
Hepatobiliary disorders
Cholecystitis Acute	0/319 (0%)		1/313 (0.3%)		0/328 (0%)
Cholecystitis Chronic	1/319 (0.3%)		0/313 (0%)		0/328 (0%)
Infections and infestations
Chronic Sinusitis	0/319 (0%)		0/313 (0%)		1/328 (0.3%)
Salmonellosis	1/319 (0.3%)		0/313 (0%)		0/328 (0%)
Tuberculosis	1/319 (0.3%)		0/313 (0%)		0/328 (0%)
Injury, poisoning and procedural complications
Contusion	0/319 (0%)		0/313 (0%)		1/328 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small Intestine Carcinoma	1/319 (0.3%)		0/313 (0%)		0/328 (0%)
Nervous system disorders
Migraine With Aura	0/319 (0%)		1/313 (0.3%)		0/328 (0%)
Renal and urinary disorders
Nephrolithiasis	1/319 (0.3%)		0/313 (0%)		1/328 (0.3%)
Renal Colic	1/319 (0.3%)		0/313 (0%)		0/328 (0%)
Reproductive system and breast disorders
Cervical Dysplasia	1/319 (0.3%)		0/313 (0%)		0/328 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/319 (0.3%)		0/313 (0%)		1/328 (0.3%)
Pulmonary Embolism	0/319 (0%)		1/313 (0.3%)		0/328 (0%)
Sinus Polyp	0/319 (0%)		0/313 (0%)		1/328 (0.3%)
Vascular disorders
Hypertension	1/319 (0.3%)		1/313 (0.3%)		0/328 (0%)
Other (Not Including Serious) Adverse Events
	Esomeprazole 40 mg Twice Daily		Esomeprazole 40 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/319 (11.6%)		44/313 (14.1%)		55/328 (16.8%)
Infections and infestations
Bronchitis	11/319 (3.4%)		16/313 (5.1%)		18/328 (5.5%)
Upper Respiratory Tract Infection	26/319 (8.2%)		28/313 (8.9%)		37/328 (11.3%)

Limitations/Caveats

Numbers of patients analyzed in each of the Outcome Measures varies due to the amount of qualifying data captured for the patients.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.