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