Trial Outcomes & Findings for Safety and Efficacy Study to Determine Anti-Asthmatic Effect of Esomeprazole Magnesium; Nexium Reflux Asthma (NCT NCT00317044)
NCT ID: NCT00317044
Last Updated: 2014-06-09
Results Overview
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.
COMPLETED
PHASE2
961 participants
Baseline to 6 months
2014-06-09
Participant Flow
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.
Participant milestones
| Measure |
Esomeprazole 40 mg Twice Daily
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
Placebo
|
|---|---|---|---|
|
Overall Study
STARTED
|
320
|
313
|
328
|
|
Overall Study
COMPLETED
|
272
|
273
|
283
|
|
Overall Study
NOT COMPLETED
|
48
|
40
|
45
|
Reasons for withdrawal
| Measure |
Esomeprazole 40 mg Twice Daily
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
Placebo
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
28
|
22
|
20
|
|
Overall Study
Adverse Event
|
4
|
7
|
4
|
|
Overall Study
Withdrawal by Subject
|
10
|
7
|
12
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
3
|
|
Overall Study
Multiple Reasons
|
6
|
2
|
6
|
Baseline Characteristics
Safety and Efficacy Study to Determine Anti-Asthmatic Effect of Esomeprazole Magnesium; Nexium Reflux Asthma
Baseline characteristics by cohort
| Measure |
Esomeprazole 40 mg Twice Daily
n=319 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=313 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=328 Participants
Placebo
|
Total
n=960 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.0 Years
n=99 Participants
|
45.0 Years
n=107 Participants
|
45.0 Years
n=206 Participants
|
44.667 Years
n=7 Participants
|
|
Sex: Female, Male
Female
|
240.00 Participants
n=99 Participants
|
240.00 Participants
n=107 Participants
|
247.00 Participants
n=206 Participants
|
727 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
79.00 Participants
n=99 Participants
|
73.00 Participants
n=107 Participants
|
81.00 Participants
n=206 Participants
|
233 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 monthsPeak 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
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).
|
21.1891 L/minute
Standard Error 2.8689 • Interval 0.0 to
|
19.1847 L/minute
Standard Error 2.8422 • Interval 0.0 to 0.0
|
15.6771 L/minute
Standard Error 2.8086 • Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsPeak 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=326 Participants
Placebo
|
|---|---|---|---|
|
Changes in Average Value From Baseline to Treatment Period in Evening Peak Expiratory Flow (ePEF (L/Minute))
|
21.88 L/minute
Standard Error 2.89
|
18.37 L/minute
Standard Error 2.87
|
18.55 L/minute
Standard Error 2.83
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsParticipants 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=315 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=326 Participants
Placebo
|
|---|---|---|---|
|
Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Total
|
-0.61 Scores on a scale
Standard Error 0.05721
|
-0.47 Scores on a scale
Standard Error 0.05652
|
-0.52 Scores on a scale
Standard Error 0.05609
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsThis 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=315 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=326 Participants
Placebo
|
|---|---|---|---|
|
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
|
-0.77 Inhalations
Standard Error 0.10 • Interval 0.0 to 17.0
|
-0.73 Inhalations
Standard Error 0.10 • Interval 0.0 to 13.0
|
-0.68 Inhalations
Standard Error 0.10 • Interval 0.0 to 14.0
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsChange 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Changes in Average Value From Baseline to Treatment Period in Percentage of Nights With Awakening(s) Due to Asthma
|
-0.238 Percent of nights
Standard Error 0.018
|
-0.219 Percent of nights
Standard Error 0.018
|
-0.223 Percent of nights
Standard Error 0.018
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=312 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=306 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=324 Participants
Placebo
|
|---|---|---|---|
|
Change in Forced Expiratory Volume in 1 Second (FEV1) From Randomization to Treatment Period.
|
0.09 Liters
Standard Error 0.02
|
0.07 Liters
Standard Error 0.02
|
0.02 Liters
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Up to 6 monthsOutcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=318 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=312 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Number of Patients With Severe Asthma Exacerbations.
|
33 Participants
|
41 Participants
|
43 Participants
|
SECONDARY outcome
Timeframe: From randomization (Visit 3) to Visit 7The 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).
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=272 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=275 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=288 Participants
Placebo
|
|---|---|---|---|
|
Change in Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) Scores From Randomization (Visit 3) to Visit 7
|
0.97 Scores on a scale
Standard Error 0.07
|
0.83 Scores on a scale
Standard Error 0.07
|
0.55 Scores on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Randomization (Visit 3) to Visit 7The 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.
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Change in Symptoms of GERD as Measured by Reflux Disease Questionnaire (RDQ) From Randomization (Visit 3) to Visit 7
|
-1.95 Scores on a scale
Standard Error 0.07
|
-1.91 Scores on a scale
Standard Error 0.07
|
-1.27 Scores on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Up to 6 monthsOutcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Number of Severe Adverse Events
|
4 Events
|
5 Events
|
9 Events
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsParticipants must have both baseline and follow up measure to be included in analysis
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Night
|
-0.31 Scores on a scale
Standard Error 0.03
|
-0.23 Scores on a scale
Standard Error 0.03
|
-0.27 Scores on a scale
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsParticipants must have both baseline and follow up measure to be included in analysis
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Changes in Average Value From Baseline to Treatment Period in Asthma Symptom Score - Day
|
-0.30 Scores on a scale
Standard Error 0.03
|
-0.25 Scores on a scale
Standard Error 0.03
|
-0.25 Scores on a scale
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsParticipants must have both baseline and follow up measure to be included in analysis
Outcome measures
| Measure |
Esomeprazole 40 mg Twice Daily
n=316 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=311 Participants
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=327 Participants
Placebo
|
|---|---|---|---|
|
Changes in Average Value From Baseline to Treatment Period in Number of Inhalations of Short-acting β2-agonists (SABAs) - Night
|
-0.30 Inhalations
Standard Error 0.05
|
-0.27 Inhalations
Standard Error 0.05
|
-0.29 Inhalations
Standard Error 0.04
|
Adverse Events
Esomeprazole 40 mg Twice Daily
Esomeprazole 40 mg Once Daily
Placebo
Serious adverse events
| Measure |
Esomeprazole 40 mg Twice Daily
n=319 participants at risk
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=313 participants at risk
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=328 participants at risk
Placebo
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/319
|
0.00%
0/313
|
0.30%
1/328
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.31%
1/319
|
0.00%
0/313
|
0.30%
1/328
|
|
Reproductive system and breast disorders
Cervical Dysplasia
|
0.31%
1/319
|
0.00%
0/313
|
0.00%
0/328
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.00%
0/319
|
0.32%
1/313
|
0.00%
0/328
|
|
Hepatobiliary disorders
Cholecystitis Chronic
|
0.31%
1/319
|
0.00%
0/313
|
0.00%
0/328
|
|
Infections and infestations
Chronic Sinusitis
|
0.00%
0/319
|
0.00%
0/313
|
0.30%
1/328
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/319
|
0.00%
0/313
|
0.30%
1/328
|
|
Vascular disorders
Hypertension
|
0.31%
1/319
|
0.32%
1/313
|
0.00%
0/328
|
|
Nervous system disorders
Migraine With Aura
|
0.00%
0/319
|
0.32%
1/313
|
0.00%
0/328
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.31%
1/319
|
0.00%
0/313
|
0.30%
1/328
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/319
|
0.32%
1/313
|
0.00%
0/328
|
|
Renal and urinary disorders
Renal Colic
|
0.31%
1/319
|
0.00%
0/313
|
0.00%
0/328
|
|
Infections and infestations
Salmonellosis
|
0.31%
1/319
|
0.00%
0/313
|
0.00%
0/328
|
|
Respiratory, thoracic and mediastinal disorders
Sinus Polyp
|
0.00%
0/319
|
0.00%
0/313
|
0.30%
1/328
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small Intestine Carcinoma
|
0.31%
1/319
|
0.00%
0/313
|
0.00%
0/328
|
|
Infections and infestations
Tuberculosis
|
0.31%
1/319
|
0.00%
0/313
|
0.00%
0/328
|
|
Gastrointestinal disorders
Umbilical Hernia
|
0.00%
0/319
|
0.32%
1/313
|
0.00%
0/328
|
Other adverse events
| Measure |
Esomeprazole 40 mg Twice Daily
n=319 participants at risk
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules twice daily
|
Esomeprazole 40 mg Once Daily
n=313 participants at risk
Nexium 40 mg given as esomeprazole magnesium trihydrate capsules once daily
|
Placebo
n=328 participants at risk
Placebo
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
3.4%
11/319
|
5.1%
16/313
|
5.5%
18/328
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
8.2%
26/319
|
8.9%
28/313
|
11.3%
37/328
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60