A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study to investigate the safety, tolerablility, pharmacokinetics (including food and gender effect), and pharmacodynamics of LNP1955 in healthy subjects.

LNP1955 is a new investigational compound that may eventually be used for the
treatment of inflammatory disease conditions such as rheumatoid arthritis.
Inflammation is an immune reaction of the body to presumed foreign substances.
In case of an auto immune response the reaction is to cells of the human body
itself. Inflammation is characterized by increased blood supply and activation
of defense mechanisms. It produces redness, swelling, heat and pain. The
compound that will be researched in this study, LNP1955, is expected to block a
protein (CRAC channel) that is involved in abnormal immune responses seen in
this type of conditions. This is the first time that this compound is being
given to humans.

The purpose of the study is to investigate to what extent LNP1955 is tolerated
and safe.
It will also be investigated how quickly and to what extent LNP1955 is absorbed
and eliminated from the body (this is called pharmacokinetics). Further, the
effect of food and gender on the pharmacokinetics will be investigated. In
addition, the effect of the compound on certain proteins in your blood will be
investigated (this is called pharmacodynamics).

SAD:
The actual study will consist of 1 period during which the subjects will stay
in the clinical research center in Groningen for 6 days (5 nights).
The subjects are expected at the clinical research center at 14:00 h in the
afternoon prior to the day of first administration of study compound. The
subjects will be required not to have consumed any food or drinks during the 4
hours prior to arrival in the clinical research center (with the exception of
water).
The subjects will leave the clinical research center on Day 5. (Day 1 is the
day of administration of study compound). The post-study screening will be
scheduled on Day 12 ± 2. The subject*s participation to the entire study, from
pre-study screening until the post study screening, will be maximally 5 weeks.


FE:
The actual study will consist of 2 periods. In each period the subjects will
stay in the clinical research center in Groningen for 6 days (5 nights).
In each period, the subjects are expected at the clinical research center at
14:00 h in the afternoon prior to the day of first administration of study
compound.
The subjects will be required not to have consumed any food or drinks during
the 4 hours prior to arrival in the clinical research center (with the
exception of water).
The subjects will leave the clinical research center on Day 5 of each period.
(Day 1 is the day of administration of study compound). The post-study
screening will be scheduled on Day 12 (± 2 days) of Period 2.
The time interval between study compound administration in the different
periods is at least 2 weeks.
The subject*s participation to the entire study, from pre-study screening until
the post study screening, will be maximally 7-8 weeks.


MAD:
The actual study will consist of 1 period during which the subject will stay in
the clinical research center in Groningen for 19 days (18 nights).
The subjects are expected at the clinical research center at 14:00 h in the
afternoon prior to the day of first administration of study compound.
The subjects will be required not to have consumed any food or drinks during
the 4 hours prior to arrival in the clinical research center (with the
exception of water).
The subjects will leave the clinical research center on Day 18. (Day 1 is the
first day of administration of study compound). The post-study screening will
be scheduled on Day 25 (± 2 days). The subject*s participation to the entire
study, from pre-study screening until the post study screening, will be
maximally 7 weeks.

Single ascending dose, multiple ascending dose, gender and food effect.

All potential drugs cause adverse events; the extent to which this occurs
differs. As LNP1955 will be administered to humans for the first time in this
study, adverse effects of LNP1955 in humans have not been reported to date.
However, based on the findings observed in animal studies, the calcium levels
in the blood may show an increase. Generally such an increase in calcium occurs
without any symptoms. However if the increase is significant, the symptoms
related to increase in calcium like nausea, vomiting, headache, increased
thirst, lethargy, weakness and inflammation might be observed. Single doses of
LNP1955 which were tested at different doses up to 60mg/kg/day were well
tolerated in rats.