TRIUMPH-2: Trientine dihydrochloride (Syprine® capsules) vs. tetrahydrochloride (tablets): a Phase 1, single center, randomized, interventional, open-label, 4-way crossover study in adult healthy male and female subjects to evaluate the pharmacokinetics and the safety and tolerability of 2 different oral formulations.

Wilson*s disease (WD) is an autosomal recessive disorder that results in
pathological copper accumulation.
Treatment of WD aims to control copper levels within acceptable limits. Dietary
control of copper intake is not sufficient in most patients, and
pharmacological treatments are therefore needed. It is generally accepted that
the most effective treatments are copper chelators which bind with copper to
form stable complexes which is then excreted in the urine. There are two
currently approved types of copper chelating agents, D-penicillamine and
trientine. gmp-orphan has developed a new trientine salt for the treatment of
WD.
The rationale for developing this tetrahydrochloride salt is that, unlike the
dihydrochloride, TETA·4HCl is stable at room temperature, has been developed as
a convenient pharmaceutical formulation for adults as well as children, and
will improve the access of this treatment to WD patients.

The primary objective of this study is to evaluate and compare the plasma PK
parameters of TETA and its two metabolites (MAT and DAT) after two dose levels
of Syprine® capsules and TETA 4HCL tablets in adult healthy male and female
volunteers.
The secondary objective is to compare the safety and tolerability of both
formulations.

This is a single center, randomized, interventional, open-label, 4-way
cross-over study to evaluate and compare the PK, safety and tolerability of two
dose levels of Trientine dihydrochloride (Syprine® capsules) vs.
tetrahydrochloride (tablets) in adult healthy male and female subjects.

The study will start with a screening visit. During the screening visit
standard medical assessments including safety laboratory tests (blood draw,
urine collection), urine drug screen, a physical examination and a vital signs
measurement will be performed.
During the study the subjects will enter the clinic, subjects will receive a
single dose medication formulation four times (4 way cross-over design), will
be asked on a regular basis for possible side effects, blood will be drawn for
safety and PK measurements and the vital signs will be checked regularly during
the 4 confinement periods.
Finally, a follow-up examination will be performed. During this visit the
subjects will be asked for possible side effects, blood will be drawn for
safety, vital signs will be checked and a physical examination will be
conducted.

This study may cause the following side effects:
- nausea, skin rash, gastrointestinal complaints
- in rare cases anaemia can occur

Small risks are related to blood sampling. Regular blood sampling can cause
minor aches and bruises at the puncture site.

The risks to health at these dose levels are limited, but subjects may
experience one of the above mentioned side-effects or other symptoms not
previously reported. The subject's health will be closely monitored during the
trial to minimize these risks.