E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe asthma and symptoms of gastroesophageal reflux disease (GERD) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the anti-asthmatic effect of esomeprazole, given either as 40 mg twice daily or 40 mg once daily, with that of placebo in adult patients with moderate to severe asthma and symptoms of gastroesophageal reflux disease (GERD) by evaluation of change in morning Peak Expiratory Flow (mPEF) 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) as the primary outcome variable. |
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E.2.2 | Secondary objectives of the trial |
Investigate the effect on symptoms of GERD when treating adult patients having moderate to severe asthma and symptoms of GERD with esomeprazole 40 mg twice daily or 40 mg once daily or placebo by evaluation of change in symptoms of GERD as measured by Reflux Disease Questionnaire (RDQ) from randomization (Visit 3) to Visit 7 to assess safety and tolerability of esomeprazole 40 mg twice daily and 40 mg once, daily for 6 months by evaluation of: - incidence, severity, and type of adverse events (AEs) - clinical laboratory tests including haematology and clinical chemistry, physical examination, vital signs including blood pressure, pulse rate and electrocardiogram (ECG). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
For inclusion in the study run-in period the patient must fulfil all of the following criteria at Visit 2: 1. Provision of written informed consent. 2. Female or male aged 18 to 70 years inclusive. 3. Clinical diagnosis of asthma as defined by the ATS definition, for at least 6 months prior to Visit 2. 4. A reversibility in FEV1 of at least 12% and ≥0.20 L from baseline after inhalation of 2 x 0.5 mg terbutaline (Bricanyl® Turbuhaler®) or 2 x 0.2 mg albuterol via a pressurized metered dose inhaler (pMDI). 5. Daily use of inhaled GCS and LABA for ≥3 months prior to Visit 2. 6. A history of at least one clinically important asthma exacerbation, as judged by the investigator, between 1 to 12 months prior to Visit 2. 7. A history of at least 3 months of 1 or more of the 3 GERD symptoms listed in inclusion criterion no 8. 8. Symptoms or history of GERD. According to scores in patient’s self-reported RDQ at least 1 of the following GERD symptoms must have a frequency of ≥ 2 days during the last week and at least 1 symptom must be of at least moderate severity:- a burning feeling behind the breastbone - pain behind the breastbone - an acid taste in the mouth - or patient must have a documented history of an abnormal esophageal 24-hourpH monitoring up to 3 years prior to Visit 2, measured by catheter basedor catheter free (BRAVO®) techniques according to the manufacturer’s instruction. The limit of percentage time of pH<4, assessed as pathological esophageal acid exposure, should be the same as the local references for respective technique.
To be randomized to the treatment period, the following criteria must be fulfilled at Visit 3:
1. Run-in diary data for at least 7 of the last 10 days of the run-in period. 2. Mean mPEF during the last 7 days of the run-in period of 50-85% of postbronchodilatory PEF. 3. Total intake of the supplied rescue medication must not exceed an acid-binding capacity of 100 mmol HCl/day during the run-in period. 4. Total asthma symptom score (night-time plus daytime) of ≥ 1 on at least 4 of the last 7 days of the run-in period. 5. Symptoms of GERD during run-in. According to scores in patient’s self-reported RDQ at least 1 of the symptoms must have a frequency of ≥ 2 of the last 7 days ofthe run-in period and at least 1 symptom must be of at least moderate severity: - a burning feeling behind the breastbone - pain behind the breastbone - an acid taste in the mouth. |
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E.4 | Principal exclusion criteria |
1. Patients with clinically relevant abnormalities at Visit 2 (ECG, vital signs, physical examination, or laboratory values), as judged by the investigator. 2. Any significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study or patient’s ability to participate in the study. 3. Patients with alarm symptoms such as unintentional weight loss, haematemesis, jaundice, dysphagia, or any other sign indicating serious or malignant disease. 4. Patients with a smoking history of ≥10 pack-year (ie, equivalent of smoking 20 cigarettes per day for 10 years). 5. Use of oral, rectal, or parenteral GCS within 30 days prior to Visit 2. 6. Patients > 50 years of age with GERD symptoms according to inclusion criterion no 8 who have not been investigated (x-ray of upper gastrointestinal tract or endoscopy) within 1 year prior to Visit 2 to exclude upper gastrointestinal tract malignant disease. 7. Patients who have had previous surgery on the esophagus or the stomach. 8. Patients with endoscopy-verified erosive esophagitis within the last 16 weeks priorto Visit 2 or Barrett’s esophagus with associated dysplasia. 9. Pregnancy or breast-feeding. Fertile women without acceptable contraceptive measures, as judged by the investigator. 10. Patients with a known hypersensitivity to any component of any PPI: esomeprazole,omeprazole, lansoprazole, rabeprazole, pantoprazole, or tenatoprazole.
Any of the following is regarded as a criterion for exclusion from the study at Visit 3: 17. A decrease in FEV1 >20% from Visit 2 and/or FEV1 <45% of the predicted normal value. 18. A clinically important asthma exacerbation, as judged by the investigator, during the run-in period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
There is no primary endpoint in this study
The primary outcome variable: Change in mPEF from baseline to treatment period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |