A SINGLE-CENTER, OPEN-LABEL, ONE-SEQUENCE, THREE-PERIOD CROSSOVER STUDY TO EVALUATE THE PHARMACOKINETICS OF HP-3040 PATCHES (TOLTERODINE TRANSDERMAL DRUG DELIVERY SYSTEM) FOLLOWING 168-HR APPLICATION COMPARED TO SINGLE-DOSE DETROL® LA 2 MG (TOLTERODINE TARTRATE EXTENDED RELEASE CAPSULE) IN HEALTHY ADULT MALE SUBJECTS

The drug to be given is an existing compound, tolterodine, in a new application
form (transdermal patches). Tolterodine is used to treat urinary incontinence.
In this study a new administration method of tolterodine, the HP-3040
transdermal patch, will be tested. This is the first time tolterodine will be
administrated to humans in this form of transdermal patches. In addition to
tolrerodine in the new application form (transdermal patches), you will receive
single dose of registered Detrol® LA (containing tolterodine tartrate) in the
form of a capsule.

The purpose of the study is to investigate how quickly and to what extent
tolterodine is absorbed and eliminated from the body (this is called
pharmacokinetics) when it is administrated by using a HP-3040 transdermal
patch. Moreover, the relative bioavailability (measurements of the amount of
drug that is actually absorbed) of tolterodine will be investigated when it is
administrated by using a HP-3040 transdermal patch. Furthermore, the
pharmacokinetic profile of HP-3040 transdermal patches will be compared to
oral administration of Detrol® LA. In addition, the safety and tolerability of
the HP-3040 transdermal patch will be investigated.

This is a single-center, open-label, 1-sequence, 3-period, comparative
crossover study in 12 healthy adult male subjects.

Procedures and assessments:
Screening and follow-up: physical examination, weight, vital signs (blood
pressure, pulse rate and body temperature), 12-lead electrocardiogram (ECG),
clinical laboratory (clinical chemistry, hematology and urinalysis) and
previous and concomitant medication

Only at screening: medical history, demographics, height, measurement of
intraocular pressure, drug and alcohol screen and serology (HBsAg, HCV and HIV)

Repeated at admission in each period: clinical laboratory (clinical chemistry,
hematology and urinalysis), drug and alcohol screen, adverse events and
previous and concomitant medication

Bloodsamping:
For PK tolterodine, 5-hydroxymethyl tolterodine and the combined active moiety
in serum:
Treatment A: before dosing untill 48 hours after dosing
Treatment B and C: before dosing untill 240 uur after dosing
For genotyping of CYP2D6: on Day 1 of period 1 (before dosing)

Residual drug:
Used patches will be collected in the labeled vials following the procedures
provided by the Sponsor and shipped
back to the Sponsor for analysis of residual ditolterodine (Treatments B and C)

Dermal assessments:
skin irritation: immediately before application untill 240 hours after
application (Treatments B, C)
discomfort: untill 168 hours after application (Treatments B, C)
patch adhesion: untill 168 hours after application (Treatments B, C)
adhesive residue at application site: immediately after patch removal
(Treatments B, C)

Safety assessments:
AEs: throughout the study
clinical laboratory assessments (including clinical chemistry, hematology and
urinalysis): prior to discharge on Day 3 (period 1) and 11 (period 2 and 3)
vital signs (including blood pressure, pulse rate and body temperature) and
ECG: pre-dose untill 48 hours postdose/
240 hours after patch application

Treatment A: one Detrol® LA, 2 mg oral capsule (2 mg tolterodine tartrate)
administered under fasting conditions
Treatment B: one HP-3040-75 transdermal patch (containing 75 mg tolterodine
tartrate) applied for 168 hours on the lower abdomen, under fasting conditions.
Treatment C: two HP-3040-75 transdermal patches (containing 150 mg tolterodine
tartrate) applied for 168 hours on the lower abdomen, under fasting conditions.

As the HP-3040 transdermal patch will be administered to man for the first time
in this study, adverse effects in man have not been reported up to now. As with
other transdermal system products, the use of the patches may occasionally lead
to symptoms of contact dermatitis such as redness, rash, eruption, flare,
itching, pigmentation, skin irritation and loss of hair at the site of
application.

Detrol® LA is a registered drug, containing tolterodine as active ingredient.
The most (frequently) reported adverse effects after administration with
capsules include dry mouth, skin and eyes, difficulty seeing, stomach and
intestinal problems, difficult urination, fatigue, headache, dizziness and
accumulation of fluid in for example the ankles, legs and arms.
Adverse effects that may occur, to a more or lesser extent, wearing one or two
transdermal patches (treatment C): abnormal heartbeat, sensitivity to light,
constipation, full bladder, decreased frequency of urination, imbalance,
reduced state of consciousness and hallucinations.

Registration af adverse effects: During the entire investigation all adverse
effect you report will be documented.

Blood draw, indwelling canula: During this study approximately 569 ml of blood
will be drawn. In period 1, blood will be drawn until 48 hours after
administration of Detrol® LA (thus until Day 3). In period 2 and 3 blood will
be drawn until 240 hours (thus until Day 11) after patch application.
It is anticipated that on Day -1 of each period an indwelling canula will be
inserted for most of the blood sampling on Day 1 and 2. On the other days
during this study, blood will be drawn by direct puncture of the vein.

Measurement of intraocular pressure (IOP): During the screening the intraocular
pressure will be measured. A trained physician will perform the measurement.
Using specific equipment, a small puff of air will be blown on to your eye.
This is not painful. You are sure to blink with your eyes and may experience a
small fright reflex. In the event that a measurement is not good due to
movement or blinking of the eye, it will be repeated.

Heart trace (ECG*s): ECG*s will be made regularly.

Blood sample for DNA tests: On Day 1 a blood sample will be taken for possible
DNA tests. Participation in this part of the study is optional. If you do not
wish to participate in this part of the study please state so on the form at
the end of this document. Refusal to participate will involve no penalty or
loss of benefits to which you would otherwise be entitled.