Phase I Multiple-Dose Safety, Pharmacokinetic and Pharmacodynamic Clinical Study of Nitric Oxide Releasing Aspirin (NCX 4016)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- At risk for colorectal cancer

- History of histologically proven sporadic colon adenomas or colon cancer

- At least 5 aberrant cryptic foci on sigmoidoscopy

- Less than 20 prior cumulative adenomas and no heredity nonpolyposis colorectal
cancer

- No significant asymptomatic lesions on sigmoidoscopy, including any of the following:

- Inflammation

- Strictures

- Anorectal lesions

- Fistulae

- Vascular lesions

- No adenomas or colon carcinomas on flexible sigmoidoscopy

- No history of gastrointestinal (GI) cancer other than colorectal cancer

- No inherited colorectal cancer syndromes

PATIENT CHARACTERISTICS:

- No other GI mucosal epithelial diseases (e.g., Barrett's esophagus, chronic or
recurrent peptic ulcer disease, celiac sprue, or other disorders of nutrient
absorption)

- No active peptic ulcer disease

- No history of inflammatory bowel disease (ulcerative colitis or Crohn's disease)

- No known or suspected alcohol ( > 5 glasses of wine or beer per day), drug, or
medication abuse

- No quantitative or qualitative platelet or coagulation abnormalities

- No personal or family history of a bleeding disorder

- No uncontrolled diabetes

- No uncontrolled hypertension, or chronic congestive heart failure (New York Heart
Association class II-IV heart disease)

- No myocardial infarction, transient ischemic attack, or stroke within the past 6
months

- No equilibrium disorders affecting gait or ability to stand that would preclude study
participation

- No involuntary change in weight (up or down) of ≥ 15% of usual body weight within the
past year

- Creatinine ≤ 2.0 mg/dL

- No chronic liver disease or pancreatitis

- No allergies to aspirin

- No prior severe adverse reactions to NSAIDs such as asthma, GI bleeding, or renal
insufficiency

- No institutionalized, mentally disabled patients

- No prisoners

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Negative pregnancy test

PRIOR CONCURRENT THERAPY:

- No concurrent antibiotic prophylaxis

- More than 7 days since prior nonsteroidal anti-inflammatory drug (NSAID) treatment,
including aspirin

- No concurrent frequent use (> 7 days in previous month) of NSAIDs, cyclooxygenase
(COX)-2 inhibitors, nitrovasodilators, or oral corticosteroids

- No concurrent macronutrient consumption below the 1st or above the 99th percentile of
U.S. consumption

- No concurrent anticoagulants, ticlopidine, and clopidogrel

- More than 3 months since prior general anesthesia

- More than 3 months since prior investigational agents

- No concurrent NSAIDs, including aspirin or COX-2 inhibitors

- Acetaminophen allowed

- No concurrent nitrovasodilating drugs

- More than 3 months since prior participation in other investigational trials