• Improvement in motor performance, measured as change in tapping speed during levodopa infusion [ Time Frame: at baseline and after 6 months ] [ Designated as safety issue: No ]
• Improvement in "on" time, as measured by subject diaries [ Time Frame: at baseline and after 6 months ] [ Designated as safety issue: No ]
• Reduction in levodopa and adjunct drug use [ Time Frame: at baseline and after 6 months ] [ Designated as safety issue: No ]

The purpose of this study is to compare the effects of apomorphine, given by two different methods, to determine how best to manage dyskinesias.

Levodopa is a drug that can be taken by mouth, and improves the symptoms of Parkinson's disease (PD). However it can eventually cause involuntary movements called dyskinesia and motor fluctuations—fluctuations in the control of symptoms, often referred to as "off" and "on." Apomorphine is a drug that works as well as levodopa, but does not work if taken by mouth.

The purpose of this study is to compare the effects of apomorphine in people with PD who have levodopa-induced motor fluctuations and dyskinesias. In the trial, researchers will compare the effects of apomorphine administered by subcutaneous bolus injections (pulsatile) and by ambulatory infusion pumps (continuous) in 24 people with PD, for 6 months.

After an initial screening, potential participants will undergo a test to verify that they can tolerate and respond to apomorphine. Those who meet all of the requirements will be randomized to receive the study drug via injections (shots) using an injector pen or a portable infusion pump. Apomorphine will be given either continuously using the portable pump during the waking day or intermittently by injection, for 6 months. The pump will be carried on a belt and connected by a tube to a small needle under the skin. Injections of apomorphine under the skin will be self-administered by the participants or administered by friends or family members using injector pens.

After 6 months, the effects of apomorphine use will be assessed by measuring how the participants respond to levodopa and by measuring their symptoms during the course of the study. Participants will be followed initially every week, then biweekly, and then monthly in an outpatient clinic for 6 months. During this time, they may receive adjustments of apomorphine doses as well as doses of other antiparkinson medications.

• Experimental: Participants will receive apomorphine via a pump. Participants in the Continuous Delivery Arm will self-administer apomorphine continuously (12-14 hours a day) using a portable pump.
• Active Comparator: Participants will receive apomorphine via an injection pen. Participants in the Intermittent Delivery Arm will self-administer apomorphine at intervals, via a injection, using pen injector.

• Manson AJ, Turner K, Lees AJ. Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson's disease: long-term follow-up study of 64 patients. Mov Disord. 2002 Nov;17(6):1235-41.
• Stocchi F, Ruggieri S, Vacca L, Olanow CW. Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease. Brain. 2002 Sep;125(Pt 9):2058-66.
• Stocchi F, Vacca L, Ruggieri S, Olanow CW. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005 Jun;62(6):905-10.

Inclusion Criteria:

• idiopathic Parkinson's Disease
• clear response to levodopa (sinemet)
• "off" at least 20% of waking day
• dyskinesias present for at least two hours of waking day
• subject or caregiver able to master use of drug delivery system (injector pen or pump)

Exclusion Criteria:

• physical complications that would preclude safe participation
• standing systolic BP of <80
• lack of tolerance or response to apomorphine
• drug/alcohol abuse