Bowman-Birk Inhibitor Concentrate in Healthy Men

OBJECTIVES:

I. Assess the toxicity of single-dose Bowman-Birk Inhibitor Concentrate (BBIC) when administered as a suspension in orange juice in healthy male participants.

II. Determine the appropriate dose range and doses to be used in a subsequent phase I multiple-dose BBIC study that will be based upon the data gathered from this phase I single-dose study.

III. Characterize the pharmacokinetics of single-dose BBIC.

OUTLINE: This is a dose-escalation study of Bowman-Birk Inhibitor Concentrate (BBIC). Participants are sequentially assigned to 1 of 4 dose level cohorts. One participant in each dose level cohort is randomized to receive placebo or BBIC.

Participants receive a single dose of oral BBIC or placebo, as an orange juice suspension, immediately followed by consumption of a defined low-fat breakfast. Participants continue to consume a low-fat diet for the next 48 hours and then resume their normal diet.

Participants undergo blood and urine sample collection periodically for pharmacokinetic studies. Samples are analyzed by a sandwich enzyme-linked immunosorbent assay to measure concentrations of BBIC and its metabolites in serum and urine.

After completion of study treatment, participants are followed once weekly for 4 weeks.

Inclusion criteria

• Healthy male participant recruited from the Philadelphia, Pennsylvania metropolitan area
• ECOG performance status 0-2
• WBC ≥ 3,000/uL
• Differential (i.e., neutrophils, lymphocytes, monocytes, bands, eosinophils, and basophils) normal
• Platelet count normal
• Hemoglobin normal
• Hematocrit normal
• RBC normal
• Creatinine normal
• Bilirubin normal
• ALT and AST normal
• Amylase and lipase normal
• Glucose normal
• Cholesterol normal
• Triglycerides normal
• Non-smoker

• Former smokers are eligible provided they have not smoked within the past 3 months
• Within 15% of ideal body weight based on standard weight tables
• No vegetarians or individuals who normally ingest large amounts of soy products, defined as two or more servings of tofu, soy milk, or other primarily soy-based food per day
• No prior allergy or adverse reaction to soybeans
• No diagnosis of cancer within the past 5 years except nonmelanoma skin cancer
• No prior diagnosis of pancreatitis, pancreatic carcinoma, pancreatic adenoma, diabetes mellitus, obstruction of pancreatic ducts, or amyloidosis
• No history of heart disease
• EKG normal (normal variants allowed)
• No evidence of psychiatric problems
• No history of excessive alcohol consumption (i.e., an average of > 2 alcoholic beverages per day)
• No alcohol consumption within the past 3 days
• No history of any medical condition that could influence gastrointestinal uptake of the drug
• No history of chronic medical condition
• No evidence of another life-threatening disease
• More than 12 months since prior chemotherapy
• More than 1 month since prior experimental drugs
• More than 2 weeks since prior and no concurrent regular use (i.e., > 3 times/week) of nonsteroidal anti-inflammatory drugs (NSAIDs)
• More than 2 weeks since prior and no concurrent multivitamin tablets (or other vitamin supplements) of > 2 per day