A randomized, open-label, crossover study to compare the ratio of pharmacokinetics between Orgaran® and Clexane® in healthy subjects with an historical study.

Orgaran® (danaparoid sodium) is a medicine that prevents blood from clotting
and to treat blood clots in blood vessels (anticoagulant). It belongs to a
group of medicines called heparinoids. Orgaran® blocks a step (Factor Xa) in
the coagulation cascade, a series of reactions in your body
which result in the formation of blood clots. Orgaran® is no new drug; it is
already available in the market since 1992. Over time, the production process
was adapted several times resulting in the question whether the compound still
has the same availability and effect in the body.
During the study the volunteers will also receive Clexane® (enoxaparin), a
similar drug used for the prevention and treatment of thrombosis and used as a
comparator in this study. Clexane® is available in the market under several
dosages.

The purpose of the study is to investigate how quickly and to what extent
Orgaran® is absorbed and eliminated from the body (this is called
pharmacokinetics) in comparison to Clexane® and in relation to the results of
the earlier studies performed with these compounds. In addition, safety and
tolerability of Orgaran® and the effect of Orgaran® on several markers related
to blood clotting will be investigated (this is called pharmacodynamics). This
study will be performed in 16 to 28 healthy male volunteers divided over 2
parts.

Part A:
The actual study will consist of 4 periods during which the volunteers will
stay in the clinical research center in Groningen (Location UMCG) for 5 days (4
nights). The time interval between the different periods is at least 3 days (at
least 6 days between subsequent study compound administrations). They are
expected at the clinical research center at 14:00 h the day before each day of
administration of the study compounds. They 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). They will leave the clinical research center on Day 4 of each period
(Day 1 is the day of administration of study compound).
The post-study visit will take place 6 - 8 days after the last administration
of study compound. The appointment for the post-study screening will be made
during the study. The participation to the entire study, from the pre-study
screening until the post-study screening, will be a maximum of 49 days (7
weeks).

Part B:
The actual study will consist of 2 periods during which the volunteers will
stay in the clinical research center in Groningen (Location UMCG) for 5 days (4
nights). The time interval between the different periods is at least 3 days (at
least 6 days between subsequent study compound administrations). They are
expected at the clinical research center at 14:00 h the day before each day of
administration of the study compounds. They 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). They will leave the clinical
research center on Day 4 of each period (Day 1 is the day of administration of
study compound). The post-study visit will take place 6 - 8 days after the last
administration of study compound. The appointment for the post-study screening
will be made during the study. The participation to the entire study, from the
pre-study screening until the post-study screening, will be a maximum of 35
days (5 weeks).

Treatment A: 1500 U Orgaran® Once
Treatment B: 2250 U Orgaran® Once
Treatment C: 3750 U Orgaran® Once
Treatment D: 40 mg Clexane® Once

Pain, minor bleedings, bruises and possibly an infection.