A SINGLE-CENTER, SINGLE-DOSE, OPEN-LABEL, THREE-WAY-CROSSOVER STUDY TO EVALUATE THE PHARMACOKINETICS OF THE HP-3070 PATCH (ASENAPINE TRANSDERMAL DRUG DELIVERY SYSTEM) FOLLOWING 24-HOUR APPLICATION COMPARED TO SINGLE-DOSE SYCREST® 5 MG (ASENAPINE, SUBLINGUAL) IN HEALTHY ADULT MALE AND FEMALE SUBJECTS

HP-3070 is a new dosing form in the form of a transdermal patch which contains
Asenapine that may eventually be used for the treatment of schizophrenia and
bipolar disorder. HP-3070 as a patch with Asenapine is not registered as a drug
and has not been given to humans before. Asenapine in an other dosing form
(sublingual tablet) however is registered as a drug en is sold in the US onder
the brand name Saphris®for the treatment of schizophrenia and bipolar disorder.
In the EU this is sold under the brand name Sycrest® for bipolar disorder only.
You will receive a patch with Asenapine twice, and once Sycrest as a sublingual
tablet.

The main purpose of the study is to investigate whether the transdermal patch
system HP-3070 shows blood concentrations of asenapine that make this route of
administration suitable for clinical use. The transdermal route of
administration is likely to improve some issues involved in the oral
administration of Asenapine such as numb feeling of the mouth / tongue. In
addition, local and general tolerability of the HP-3070 transdermal patch and
general tolerability of Sycrest® will be investigated.

HP-3070 3-way crossover PK study in which the dosing of asenapine as a patch
application is compared with the dosing of asenapine as a sublingual tablet

period 1: sublingual tablet with asenapine dosed once on dag 1
period 2: transdermal patch application with 3.6 mg asenapine for 24 hours on
day 1
period 3: transdermal patch application with 4.8 mg asenapine for 24 hours on
day 1

During this study several assessments will be performed that may be considered
as a burden.

Asenapine has never been administered to humans through the HP-3070 system.
Though local tolerability was good in animal experiments, local skin irritation
may be a side-effect of HP-3070 patches.

Asenapine administered through a sublingual tablet has well-documented side
effects of which the most important are: sleepiness, dizziness, postural
dizziness / fainting, anxiety, oral numbness / numbness of the tongue / oral
paraesthesia (tingling / burning sensation), spasm of the tongue, abnormal
taste, akathisia (motor restlessness, inability to sit still), dystonia
(involuntary muscle contractions that cause twisting and repetitive movements
or abnormal postures), muscular stiffness, low blood pressure. To a lesser
extent: hypersensitivity reactions including anaphylaxis, slow pulse rate /
abnormal heart rhythm.

With the doses used in this study no serious adverse effects are expected. The
occurrence of known or other (unknown) effects cannot be excluded. All
potential drugs cause adverse events to some extent. Therefore subjects should
take into account that some risks are still unknown at this moment