A Phase 1 Study to Compare the Pharmacokinetics of CAL-101 Capsules to Tablets in Healthy Male Subjects.

The drug CAL-101 to be given is a new, investigational compound that may
eventually be used for the treatment of leukemia and lymphoma.
Leukemia and lymophoma are both diseases of the blood, in particular the white
blood cell. In leukemia typically there is an excessive increase of immature
white blood cells. Normally a white blood cell matures and after a certain
period it dies and is replaced by a new white blood cell. In lymphoma, the
white cells begin to multiply uncontrollably, producing cancerous cells that
have the abnormal capacity to invade other tissues throughout the body. It has
been found that with leukemia and lymphoma white blood cells survive longer,
because among other things they have an increased activity for an enzyme called
p110 delta. If this enzyme, p110 delta, is inhibited by CAL-101, the leukemia
and lymphoma cells may die off. In animals given high doses of CAL-101, effects
were seen mainly on cells of the bone marrow and the liver. In an ongoing study
of patients with leukemia and lymphoma a number of signs have been seen for the
possible treatment of these illnesses.

Primary: to evaluate the pharmacokinetics of a single 100 mg dose of CAL-101
administered as a capsule (unmicronized formulation), a capsule (micronized
formulation) or a tablet in normal healthy male subjects
Secondary: to evaluate the safety of a single 100 mg dose of CAL-101 in healthy
male subjects

Design: a randomized, three-period crossover study.

Procedures and assessments
Screening and follow-up: clinical laboratory, vital signs, physical
examination, ECG; at eligibility screening: medical history, height, weight,
drug screen, HBsAg, anti HCV, anti-HIV 1/2; follow-up at discharge on Day 12;
drug screen, vital signs, ECG, haematology and clinical chemistry to be
repeated upon admission
Observation period: one period in clinic from -17 h before drug administration
on Day 1 up to 72 h after drug administration on Day 9
Blood sampling: for pharmacokinetics of CAL-101 in plasma: pre-dose and 15, 30
min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h post-dose on Days 1, 5 and 9
Safety assessments: adverse events: throughout the study; vital signs: once on
Days 1-11
Bioanalysis: analysis of plasma CAL-101 samples using a validated method by PRA

Active substance: CAL-101

Procedures: pain, light bleeding, heamatoma, possibly an infection.