Pharmacokinetics and -dynamics of needlefree apomorphine administration vs. subcutaneous injections with apomorphine in patients with Parkinson*s disease; a pilot study with a new device

Apomorphine (Apo-go) pen-ject therapy is a well established, effective and safe
rescue therapy for off-periods in Parkinson*s disease (PD). However, one
disadvantage of this therapy is the subcutaneous injection of apomorphine,
which creates a psychological barrier for some patients to use this rescue
opportunity and the injections can cause subcutaneous irritation. Another
problem for some patients is injecting themselves during an off-phase, which
may create practical hurdles due to for instance rigidity and/or tremor.
Recently a new needlefree injection technique was introduced, which may benefit
PD patients having problems or subcutaneous irritation with the use of the
currently available pen-ject system (Apo-go). To test if the new needlefree
system delivers apomorphine as good as the current Apo-Go system in PD
patients, with possibly less skin irritation, a bioequivalence study was
designed. Hypothesis: Needleless apomorphine delivery is as effective as the
current Apo-go system in patients with Parkinson*s disease, is easier to use
and gives less skin irritation in Parkinson's patients.

Primary Objective: To compare the pharmacokinetics of the needlefree system
with the Apo-go penject. Secondary objectives: - To assess the clinical effect
of Apo-go vs. de needlefree system, using an "automated tap score" and a "Timed
Up and Go test" - To assess the safety profile of Apo-go and the needlefree
system, focusing especially on the skin redness and irritation - To assess the
patient satisfaction with the new needlefree system.

It concerns an intervention study in which the needlefree injection system will
be compared with the Apo-go penject system. 1. Patients will be screened at the
department of Neurology. 2. Admission to the hospital for 2 days. 3. Patients
will not use anti-Parkinson medication from midnight until the first study
injection the next day, when they will be in an off-period. Patients will
inject the apomorphine themselves, unless they are inable to do so. In that
case the researcher will inject the patient for them (this will be taken into
account when analyzing patient satisfaction). 4. Sampling of apomorphine plasma
concentrations via an intravenous catheter, according to a fixed time schedule
(t=0,3,6,9,12,15,20,30,45,60,90,120 minutes) after apomorphine administration.
Patients will be randomized for the method of administration received at day
one and two. 5. Clinical effectiveness will be assessed by means of the
automated tapscore (directly after sampling) and by means of the "Timed Up and
Go test" at (t=0,10,20,30,45,60,90,120 minutes). 6. Assessment of AE
questionnaires at baseline and after the final sampling time. 7. Assessment of
qualitative Erythema Scale and Minolta erythema assessment at baseline and
after the final sampling time. 8. Questionnaire regarding patient satisfaction
will be filled out after the final blood sampling has taken place. 9.
Pharmacokinetic data will be analyzed at the Medisch Spectrum Twente in
Enschede, at the lab of the hospital pharmacy (dr. Chris Movig).

The intervention is the administration of apomorphine via the needlefree
system. The Apo-go penject administration serves as a comparator, as this is
the standard method of administration of apomorphine during off-phases in
Parkinson*s patients.

A two-day admission to the hospital is required. Patients may experience the
well-known AE*s of apomorphine, especially nausea, hypotension and subcutaneous
inflammation. However, all included patients will be monitored for these AE*s
very carefully and continuously during their admission. Furthermore the
placement of intravenous catheters may cause local irritation, bleeding and/or
infection.