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

Phase 1
50 Years
Not Enrolling
Colorectal Cancer

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Trial Information

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



- Evaluate the effects of nitric oxide-releasing acetylsalicyclic acid on aberrant
cryptic foci (ACF) in patients at high risk for colon cancer.


- Determine the pharmacokinetic profile of this drug in these patients.

- Determine the presence or absence of ACF in these patients.

- Determine the expression of PGE2, COX-1, COX-2, NF-kB, and β-catenin in colon tissue.

- Determine the safety and tolerability of long-term nitric oxide-releasing
acetylsalicyclic acid in these patients.

OUTLINE: This is a multicenter, double-blind, randomized, placebo-controlled, parallel group
study. Patients are stratified according to gender and race (black vs non-Hispanic white vs
Hispanic white vs Asian). Patients are randomized to 1 of 3 treatment arms.

- Arm I: Patients receive oral nitric oxide-releasing acetylsalicyclic acid twice daily
for 6 months.

- Arm II: Patients receive nitric oxide-releasing acetylsalicyclic acid twice daily for 6
months at a higher dose than in arm I.

- Arm III: Patients receive oral placebo twice daily for 6 months. Patients undergo
sigmoidoscopies at baseline and at the completion of study treatment. Biopsies of
aberrant cryptic foci (ACF) and non-ACF sites are collected at both sigmoidoscopies.
Tissue is examined for biomarkers (PGE_2, COX, NF-kB, β-catenin).

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 240 patients will be accrued for this study.

Inclusion Criteria


- 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

- 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


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

- 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

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

- 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

- No institutionalized, mentally disabled patients

- No prisoners

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Negative pregnancy test


- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Outcome Measure:

Effects of nitric oxide-releasing acetylsalicyclic acid (NCX 4016) on aberrant cryptic foci (ACF) multiplicity after the second dose at 6 months

Safety Issue:


Principal Investigator

Basil Rigas, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stony Brook University


United States: Food and Drug Administration

Study ID:




Start Date:

July 2006

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • colon cancer
  • rectal cancer
  • Colorectal Neoplasms



Stony Brook University Cancer Center Stony Brook, New York  11794-8174