A randomized, double-blind, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetics and food effect of orally administered LYC-30937 in healthy male subjects

LYC-30937 is a new investigational compound that may eventually be used for the
treatment of ulcerative colitis, which is a form of inflammatory bowel disease
(IBD). Ulcerative colitis is a condition that causes chronic inflammation and
ulceration of the lining (mucosa) of the large intestine. This condition is
commonly treated with medication to suppress local inflammation
(5-aminosalicylic acid [5-ASA] drugs, or corticosteroids) or the entire immune
system (immunosuppressants), which are both known to have many side effects.
The new investigational compound LYC-30937 affects a specific enzyme (ATPase),
which is involved in the energy supply to a subset of white blood cells that
facilitate the disease. This is the first time that LYC-30937 is being given to
humans.

The purpose of the study is to investigate the safety of LYC-30937 and to what
extent LYC-30937 is tolerated. It will also investigate how quickly and to what
extent LYC-30937 is absorbed and eliminated from the body (this is called
pharmacokinetics). Furthermore the effect of food on the pharmacokinetics of
LYC-30937 will be investigated.

Study design:
Part A: single asending doses
Part B: multiple ascending doses
Part C: food-effect part

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Procedures: pain, light bleeding, haematoma, possibly an infection

In Part A of the study, a total of 33 healthy volunteers received a single dose
of LYC 30937 or placebo at a dose of 2 to 300 mg. Only few adverse events were
reported by these volunteers and they were all of mild intensity. Six
volunteers reported adverse events which were considered to be possibly related
to LYC 30937. One of these volunteers reported a hot feeling and the remaining
adverse events were related to the gastro-intestinal tract, including
flatulence (reported by 2 volunteers), abdominal pain, loose stools and
diarrhea. At this moment it is unknown whether the latter adverse events were
reported by volunteers receiving LYC 30937 or placebo.

When LYC 30937 was administered daily to monkeys at doses of 3 to 30 mg/kg for
28 days, no adverse events were observed at the lowest dose level (3 mg/kg).
The most frequently observed adverse events at doses of 10 or 30 mg/kg included
vomiting, reduced appetite, bristling hair, pale skin, hunched posture,
drooping of the eyelid, weakness, abdominal swelling, decreased activity,
reduced body temperature, diarrhea and dehydration. In addition, some transient
changes in blood components and liver enzymes were noted. Of the 12 monkeys who
received the highest dose, one animal was killed after 16 days and 3 animals
were killed after 19 days because of a deteriorating condition. The remaining
animals completed the study.