Sulindac Capsules Compared With Sulindac Tablets in Healthy Volunteers

OBJECTIVES:

Primary

• Compare the systemic exposure of sulindac tablets vs sulindac capsules in healthy volunteers.

Secondary

• Compare the terminal half-life and time of peak drug concentration of sulindac tablets vs sulindac capsules.

OUTLINE: This is a randomized study. Participants are randomized to 1 of 2 treatment arms.

• Arm I: Participants receive one sulindac capsule followed 7-10 days later by one sulindac tablet.
• Arm II: Participants receive one sulindac tablet followed 7-10 days later by one sulindac capsule.

Blood is collected periodically during treatment for pharmacokinetic studies.

After completion of study therapy, participants are followed at 7-10 days.

PROJECTED ACCRUAL: A total of 28 participants will be accrued for this study.

DISEASE CHARACTERISTICS:

• Healthy volunteer

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Hemoglobin ≥ 12.0 g/dL (women)
• Hemoglobin ≥ 13.5 g/dL (men)
• WBC > 3,000/mm³
• Platelet count > 100,000/mm³
• Absolute neutrophil count > 1,500/mm³
• Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• ALT ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 30 mL/min
• No history of allergic reactions or hypersensitivity to sulindac or other NSAIDs, including aspirin-sensitive asthma or urticaria
• No condition that interferes with ingestion or absorption of oral medications
• No cancer within the past 3 years except nonmelanomatous skin cancer, localized prostate cancer, carcinoma in situ of the cervix, or superficial bladder cancer that was previously treated > 6 months ago
• No uncontrolled concurrent illness including, but not limited to, the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Myocardial infarction in the past 6 months
• Chronic renal disease
• Chronic liver disease
• Hypertension that is difficult to control
• Psychiatric illness or social situations that would limit study compliance
• No other significant clinical disorder or laboratory finding that would preclude study participation
• No consumption of alcoholic or caffeinated beverages for ≥ 24 hours prior to study drug administration and until all blood samples have been drawn
• Willing to provide required biologic specimens

PRIOR CONCURRENT THERAPY:

• More than 6 months since prior investigational agents
• More than 6 months since prior regular use of (defined as a frequency of 7 consecutive days for > 3 weeks or > 21 days total) or other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2 inhibitors including, but not limited to, the following:

• Ibuprofen
• Ketoprofen
• Naproxen
• More than 6 weeks since prior oral corticosteroids
• More than 30 days since prior and no concurrent use of any of the following:

• Methotrexate
• Corticosteroids
• Warfarin
• Ticlopidine
• Clopidogrel
• Low molecular weight heparins
• Abciximab
• Dipyridamole
• Eptifibatide
• Tirofiban
• Lithium
• Cyclosporine
• Hydralazine
• Angiotensin-converting enzymes (ACE) inhibitors

• ACE-receptor antagonists allowed
• Angiotensin-receptor blockers
• Ginkgo
• Ketorolac
• Levofloxacin
• Loop diuretics
• Meadowsweet
• Selective serotonin reuptake inhibitors
• Danaparoid
• No concurrent regular aspirin use unless prescribed by a physician for prevention

• A maximum of one aspirin (81 mg/day) allowed
• No concurrent herbal products (e.g., saw palmetto or Hypericum perforatum [St. John's wort])