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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2009

Intervention(s) in this Clinical Trial

• Drug: CGT-2168 (clopidogrel 75 mg/omeprazole 20 mg) and aspirin
  • (CGT-2168 active and Comparator placebo, one capsule each daily; and enteric coated aspirin at daily dose level assigned by study physician)
• Drug: Plavix (clopidogrel 75 mg) and aspirin
  • (CGT-2168 placebo and Comparator active, one capsule each daily; and enteric coated aspirin at daily dose level assigned by study physician)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Active Comparator: 2

Primary Measures

• Composite of upper gastrointestinal clinical events, including gastroduodenal bleeding, symptomatic gastroduodenal ulcer, persistent pain with multiple gastric erosions, obstruction or perforation
  • Time Frame: Minimum of 48 weeks, up to 96 weeks
    Safety Issue?: No

Secondary Measures

• Composite of gastroduodenal bleeding, symptomatic gastroduodenal ulcer, obstruction or perforation
  • Time Frame: Minimum of 48 weeks, up to 96 weeks
    Safety Issue?: No
• Composite of gastroduodenal bleeding, obstruction or perforation
  • Time Frame: Minimum of 48 weeks, up to 96 weeks
    Safety Issue?: No
• Discontinuation of study medication attributed to gastrointestinal signs or symptoms
  • Time Frame: Minimum of 48 weeks, up to 96 weeks
    Safety Issue?: No
• Gastroesophageal reflux disease, as evidenced by symptomatic endoscopically-confirmed erosive esophagitis
  • Time Frame: Minimum of 48 weeks, up to 96 weeks
    Safety Issue?: No
• Dyspepsia, defined as an increase of at least ten points on the "pain intensity" component of the SODA instrument from baseline
  • Time Frame: Minimum of 48 weeks, up to 96 weeks
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Cogentus Pharmaceuticals

Overall Clinical Trial Officials and Contacts

Pablo Lapuerta, MD Study Director Cogentus Pharmaceuticals  

Overall Contact: Pablo Lapuerta, MD 650-543-4730 clinicaltrials@cogentus.net

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00557921

Study ID Number: CG104

ClinicalTrials.gov Identifier: NCT00557921

Health Authority: United States: Food and Drug Administration