Clopidogrel and the Optimization of Gastrointestinal Events (COGENT-1)

Study Overview
=================
Brief Summary
-----------------
The purpose of the COGENT-1 clinical trial is to determine whether CGT-2168 (clopidogrel and omeprazole) compared to clopidogrel is safe and effective in reducing the incidence of gastrointestinal bleeding and symptomatic ulcer disease, in the setting of concomitant aspirin therapy. Antiplatelet therapy is an essential element of care for patients with atherothrombotic disease. Bleeding is a fundamental adverse effect of all antiplatelet drugs including aspirin, clopidogrel and dual antiplatelet regimens. The gastrointestinal tract is the most common site of bleeding related to antiplatelet therapy, typically in connection with peptic ulcer disease. Recently published studies suggest the use of clopidogrel carries a gastrointestinal bleeding risk similar to that of aspirin or non-aspirin non-steroidal anti-inflammatory drugs. Patients taking any two of these drugs (clopidogrel, aspirin and/or non-aspirin NSAIDs) are exposed to an even higher risk of bleeding and ulcer disease. Cogentus Pharmaceuticals is launching phase 3 trials of a novel combination product, CGT-2168, which has the potential to significantly reduce this problem and increase patient safety. CGT-2168 combines a standard dosage of clopidogrel and a gastroprotectant (omeprazole) in a once-daily pill that may reduce the likelihood of adverse gastrointestinal events.

Official Title
-----------------
A Randomized, Double-Blind, Double-Dummy, Parallel Group, Phase 3 Efficacy and Safety Study of CGT-2168 Compared With Clopidogrel to Reduce Upper Gastrointestinal Events Including Bleeding and Symptomatic Ulcer Disease

Conditions
-----------------
Acute Coronary Syndrome, Myocardial Infarction, Coronary Artery Disease, Percutaneous Coronary Intervention

Intervention / Treatment
-----------------
* Drug: CGT-2168 (clopidogrel 75 mg/omeprazole 20 mg) and aspirin
* Drug: Plavix (clopidogrel 75 mg) and aspirin


Participation Criteria
=================
Eligibility Criteria
-----------------
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. 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. Exclusion Criteria: Patients 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 that cannot be safely discontinued for duration of study. Recent fibrinolytic therapy. 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 time of randomization, refractory ventricular arrhythmias, or congestive heart failure (NY 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. Systemic corticosteroids except low-dose oral corticosteroids equivalent to prednisone < or equal to 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 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. Laboratory abnormality at screening that is clinically significant or outside protocol-allowed limits, or any other condition that precludes participation in the study in the opinion of the Investigator.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: CGT-2168 (clopidogrel 75 mg/omeprazole 20 mg) and aspirin<br>* (CGT-2168 active and Comparator placebo, one capsule each daily; and enteric coated aspirin at daily dose level assigned by study physician)<br>|
| Active Comparator: 2<br> | Drug: Plavix (clopidogrel 75 mg) and aspirin<br>* (CGT-2168 placebo and Comparator active, one capsule each daily; and enteric coated aspirin at daily dose level assigned by study physician)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of upper gastrointestinal clinical events, including gastroduodenal bleeding, symptomatic gastroduodenal ulcer, persistent pain with multiple gastric erosions, obstruction or perforation |  | Anticipated minimum of 48 weeks, up to end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of gastroduodenal bleeding, symptomatic gastroduodenal ulcer, obstruction or perforation |  | Anticipated minimum of 48 weeks, up to end of study | 
| Composite of gastroduodenal bleeding, obstruction or perforation |  | Anticipated minimum of 48 weeks, up to end of study | 
| Discontinuation of study medication attributed to gastrointestinal signs or symptoms |  | Anticipated minimum of 48 weeks, up to end of study | 
| Gastroesophageal reflux disease, as evidenced by symptomatic endoscopically-confirmed erosive esophagitis |  | Anticipated minimum of 48 weeks, up to end of study | 
| Dyspepsia, defined as an increase of at least ten points on the pain intensity component of the SODA instrument from baseline |  | Anticipated minimum of 48 weeks, up to end of study | 
| Occurrence of a cardiovascular event (cardiovascular death, nonfatal myocardial infarction, CABG or PCI, or confirmed ischemic stroke |  | Anticipated minimum of 48 weeks, up to end of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ACS, CAD, MI, PCI, PTCA, NSTEMI, STEMI, acute coronary syndrome, cerebrovascular disorders, coronary artery stent placement, coronary thrombosis, myocardial infarction, myocardial ischemia, percutaneous coronary intervention, percutaneous transluminal coronary angioplasty, peripheral vascular diseases, duodenal obstruction, duodenal ulcer, dyspepsia, esophagitis, peptic, gastric outlet obstruction, gastroduodenal ulcer, gastroesophageal reflux disease, gastrointestinal hemorrhage, peptic ulcer, peptic ulcer perforation