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.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Effects of nitric oxide-releasing acetylsalicyclic acid (NCX 4016) on aberrant cryptic foci (ACF) multiplicity after the second dose at 6 months
Basil Rigas, MD
Stony Brook University
United States: Food and Drug Administration
|Stony Brook University Cancer Center||Stony Brook, New York 11794-8174|