E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastrointestinal events including bleeding in patients receiving dual anti-platelet therapy (clopidogrel and aspirin) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10018012 |
E.1.2 | Term | Gastrointestinal signs and symptoms |
|
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 main objective of this study is: To determine if CGT-2168 compared to clopidogrel increases the time to a composite endpoint of upper gastrointestinal events including bleeding and symptomatic gastroduodenal ulcer disease, in the setting of concomitant aspirin.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives of the trial are: 1. To determine if CGT-2168 compared to clopidogrel increases the time to discontinuation of study medication due to gastrointestinal signs or symptoms in the setting of concomitant aspirin.
2. To determine if CGT-2168 compared to clopidogrel increases the time to development of gastroesophageal reflux disease/erosive esophagitis and dyspepsia, in the setting of concomitant aspirin.
3. To evaluate the safety of CGT-2168 compared to clopidogrel, in the setting of concomitant aspirin.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
Patients must meet all inclusion criteria • Patients in whom a requirement for clopidogrel therapy with concomitant aspirin is anticipated for at least the next 12 months. Specific conditions that may confer a need for long-term clopidogrel + aspirin therapy may include non-ST segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI), ST segment elevation acute MI), or new placement of a coronary artery stent. • Age ≥ 21 years. No more than 40% of participants will be less than 65 years of age at randomization. • For women of childbearing potential, negative pregnancy test prior to randomization and agreement to use effective method of birth control during the study. • Able to provide written informed consent based on competent mental status.
|
|
E.4 | Principal exclusion criteria |
Exclusion Criteria:
Any of the criteria will result in exclusion • Patients who are currently hospitalized for whom discharge is not anticipated within 48 hours of randomization. • Requirement for current or chronic use of a proton pump inhibitor, H2 receptor blocker, sucralfate or misoprostol. • Erosive esophagitis, esophageal or gastric variceal disease, or non-endoscopic gastric surgery. Patients with a history of GERD/erosive esophagitis or dyspepsia who do not currently require proton pump blockers will be eligible. • Receipt of > 21 days of clopidogrel or another thienopyridine prior to randomization. • Oral anticoagulation with vitamin K antagonists (coumarins) that cannot be safely discontinued for duration of study. • Recent fibrinolytic therapy (for fibrin-specific and nonfibrin-specific agents, administration < 24 hours and < 48 hours before randomization, respectively). • Scheduled percutaneous coronary intervention (PCI). Patients may be enrolled upon completion of PCI. • Recent (< 30 days prior to randomization) or scheduled coronary artery bypass graft (CABG) surgery. • Cardiogenic shock at the time of randomization, refractory ventricular arrhythmias, or congestive heart failure (New York Heart Association class IV). • Active pathological bleeding or a history of hereditary or acquired hemostatic disorder. • History of hemorrhagic stroke, intracranial neoplasm, arteriovenous malformation or aneurysm. • Platelet count < 100,000/mL at screening. • Anemia (hemoglobin < 10 g/dL) at screening. • Systemic corticosteroids except low-dose oral corticosteroids equivalent to prednisone ≤ 5 mg/day. • Allergy or contraindication to clopidogrel or other thienopyridine drugs, omeprazole or other proton pump inhibitor drugs, aspirin or salicylate derivatives, or other study drug ingredients. • Treatment within 30 days prior to randomization with any investigational drug or device including investigational (not approved) coronary artery stents, or currently enrolled in another interventional drug or device study. • Women who are pregnant or breastfeeding. • Life expectancy less than 12 months. • Clinically significant laboratory abnormality at screening or any other condition that, in the opinion of the Investigator, precludes participation in the study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the time from randomization to first occurrence of a composite endpoint of upper gastrointestinal clinical events, including: 1. Upper gastrointestinal bleeding, including bleeding of gastroduodenal origin and acute upper gastrointestinal bleeding of unknown origin; 2. Bleeding of presumed occult gastrointestinal origin with documented decrease in hemoglobin of ≥ 2 g/dL or decrease in hematocrit ≥ 10% from baseline; 3. Symptomatic gastroduodenal ulcer confirmed by endoscopy or radiography without evidence of gastrointestinal bleeding; 4. Persistent pain of presumed gastrointestinal origin (duration ≥ 3 days) with underlying multiple erosive disease (5 or more gastroduodenal erosions, excluding mucosal hemorrhages), confirmed by endoscopy; 5. Obstruction; or 6. Perforation.
|
|
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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 225 |
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 | Yes |
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
|
The end of trial will be based on the projected date at which 147 primary endpoint events (first occurrence of a composite endpoint of upper GI clinical events) will be reached, as determined by the study sponsor. There will be one formal interim analysis for efficacy. This will be reviewed by the independent DMC who may recommend stopping the study if the efficacy stopping criterion is achieved. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |