E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Target subject population are male and female subjects requiring low-dose acetylsalicylic acid (75-325 mg daily) who are Helicobacter pylori negative and who are at increased risk of developing gastroduodenal ulcers. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017886 |
E.1.2 | Term | Gastroduodenal ulcer |
|
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 the study is to compare the effect of esomeprazole 20 and 40 mg once daily (od) versus placebo on the occurrence of peptic ulcers during 26 weeks in subjects on continuous low-dose acetylsalicylic acid (ASA). |
|
E.2.2 | Secondary objectives of the trial |
Compare the effect of esomeprazole 20 and 40 mg od versus placebo on
1+2. the occurrence of duodenal and gastric ulcers during 26 weeks in subjects on continuous low-dose ASA. 3. subject- reported dyspeptic symptoms at the 26-week visit or the last visit, unless the last visit is the baseline visit, assessed by Reflux Disease Questionnaire (RDQ) in subjects on continuous low-dose ASA. 4. subject- reported gastroesophageal reflux disease (GERD) symptoms (heartburn and regurgitation) at the 26-week visit or the last visit, unless the last visit is the baseline visit, assessed by RDQ in subjects on continuous low-dose ASA.
5. Study the number of gastric and/or duodenal erosions during 26 weeks in subjects on continuous low-dose ASA, by treatment. 6. Assess safety and tolerability of treatment with esomeprazole 20 and 40 mg od during 26 weeks in subjects on continuous low-dose ASA.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of written informed consent. 2. Physician prescribed or recommended daily intake of low-dose aspirin (75-325 mg daily) that is expected to continue for the duration of the study (daily intake is defined as at least ≥5 days per week). 3. The subject must fulfill at least one of the following (a-e): a) Aged ≥65 years. b) Aged ≥18 years and with a documented history of uncomplicated peptic ulcer(s). c) Aged ≥60 years and naïve to low-dose aspirin (ie, treatment started within 1 month prior to randomization). d) Aged ≥60 years with stable coronary artery disease. e) Aged ≥60 years with complains of upper GI symptoms that, as judged by the investigator, requires an EGD and with the finding of ≥5 gastric and/or duodenal erosions at the baseline endoscopy. 4. H. pylori negative. (H. pylori test to be performed according to local routines. Eradication treatment completed at least 4 weeks prior to randomization is allowed.). 5. Able to read and write.
|
|
E.4 | Principal exclusion criteria |
1. Reflux esophagitis Los Angeles (LA) classification grade C or D at baseline EGD or within the last year as known by the investigator, or severe esophagitis within the last year as known by the subject (for definition, see Section 4.6.1.1). 2. Peptic ulcer(s) at baseline EGD. 3. History of peptic ulcer complications such as clinically significant bleeding and/or perforation. 4. Any previous surgery of the stomach and/or the duodenum (except for laparoscopic fundoplication). 5. Any of the following vascular diseases: - Unstable hypertension - History of Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Graft (CABG) within the last 3 months - Clinically relevant valvular disease - Serious cardiac failure: New York Heart Association Functional Classification II–IV (NYHA II-IV), Ejection Fraction (EF) <40 % - Cerebrovascular accident within the last 3 months. 6. Any current or historical evidence of the following diseases/conditions: - Malabsorption - Known esophageal stricture - Known Barrett’s esophagus with documented dysplastic changes of any grade - Zollinger-Ellison syndrome - Signs and symptoms of gastric outlet obstruction (eg, abdominal distension or multiple episodes of vomiting) - Pancreatitis - Unstable diabetes mellitus (as judged by the investigator). Stable diabetes controlled by diet, oral agents or insulin is acceptable - Atrophic gastritis - Short bowel syndrome. 7. Evidence of any malignant disease within the last 5 years, except minor superficial skin disease. 8. Continuous treatment with a NSAID including a cyclooxygenase-2 (COX-2)- selective NSAID during the last 2 months prior to randomization. During this period occasional use up to 1 day/per week is allowed. 9. Ongoing anticoagulant therapy, such as warfarin or other vitamin K antagonists. Antiplatelets such as clopidogrel are allowed. 10. Need for concomitant therapy with medication that could interact with esomeprazole, ie, phenytoin, ketoconazole, itraconazole, voriconazole, cisapride, atanzanavir, ritonavir. 11. Known or suspected intolerance or hypersensitivity to esomeprazole or other PPIs or aspirin. 12. Any use of a PPI or prostaglandin analogue within 14 days prior to the baseline EGD and between baseline EGD and randomization, or daily use of a histamine H2-receptor antagonist during the last 14 days prior to the baseline EGD (occasional use of H2-receptor antagonist less than daily is permitted during this period). 13. Need for continuous concurrent therapy with: - Prostaglandin analogues - Sucralfate. 14. Any condition that, in the opinion of the investigator, may either put the subject at risk or influence the result of the study (eg, cardiogenic shock or severe haemodynamic instability, risk for non-compliance, risk for being lost to follow-up), as judged by the investigator. 15. Pregnancy, planned pregnancy or lactation. Women of childbearing potential must use reliable and medically accepted methods of birth control, as judged by the investigator. 16. Alcohol and/or drug abuse or any other condition associated with poor compliance, as judged by the investigator. 17. Use of any other investigational compound or participation in another clinical study within the last 30 days prior to randomization. 18. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the study site). 19. Previous enrolment or randomization in the present study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Development of a gastric and/or a duodenal ulcer. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
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 | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
End of study is defined as database lock, which is the time point after which no subjects will be exposed to study-related activities. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |