Investigation of the applicability of dry powder inhalation in patients with Parkinson*s disease.

Because of limited treatment options with a very rapid onset for Parkinson*s
disease patients in the off period, there is a need for the development of
rapid onset options to administrate levodopa (rescue therapy), like a pulmonary
formulation of levodopa. Rescue therapy is used on an acute, as-needed basis to
return patients to an on state when they are experiencing an off state. Rescue
therapy aims at a rapid return to an on state in patients with wearing off or
patients with early morning akinesia.

The development of a dry powder inhaler (DPI) that suits the needs of
Parkinson*s patients, based on their inspiratory capacities, is essential. In
this study, we will investigate the applicability of dry powder inhalation in
Parkinson*s patients in order to enable us to develop a DPI specifically for
this patient group.

To determine if a Parkinson*s patient can operate a test inhaler correctly
during off periods, by testing if they can generate a sufficiently large
airflow and volume through the test inhaler theoretically necessary to disperse
a medicinal powder and transport the aerosol into the lower airways during an
off period.

The study is a non-therapeutic observational study in which the applicability
of dry powder inhalation in Parkinson*s patients will be investigated. The
study will be conducted with an instrumented test inhaler. The test inhaler
concept is a dummy, without any drug substance or excipient. It is equipped
with a pressure drop meter to record the inhalation curve of the patient.

In order to be able to measure during an off period, patients will be asked to
postpone a dose of levodopa until they become off. As soon as the patient
starts feeling off, explanation of the test procedure will be started. Because
becoming off is not one fixed point in time but will take a while, a 15 minute
waiting period before start of the inhalation test will be taken. During this
waiting period, the researcher will explain the test procedure. The patient
will receive instructions on how to use the test inhaler. The instructions will
be given orally and partly be demonstrated by the instructor, partly be
visualised by photographs and recordings of generated flow curves on a computer
screen. 15 minutes after the patients started to feel off, a motor function
examination (conform UPDRS III) will be performed. As soon as the UPDRS III is
greater than or equal to 30, the inhalation test will be started. After the
patient finished the test inhalations, the patient will take his/her levodopa.

The inhaler used is a specially designed dummy without drug or excipient, so
the Parkinson*s patient will not inhale anything but air during the test. The
burden is minimal as the procedures are limited to the performance of a couple
of inhalations (maximum 10). Per Parkinson*s patient, the test is limited to
one test moment that lasts maximally 30 minutes per test moment. This
observational study has no specific benefits for the participating Parkinson*s
patients. Only when performed in this population, information on the
inspiratory capacities of Parkinson*s patients can be obtained. Since all
patients included are familiar with frequent off episodes, no new discomfort
compared to other off episodes is expected. The timeframe between the morning
levodopa dose and the postponed levodopa dose is expected to be shorter than
the levodopa free period during the night. The patients are used to a levodopa
free period and the effect of this levodopa free period on their motor
function.