Study of LY300164 for the Treatment of Parkinson's Disease
Study of LY300164 for the Treatment of Parkinson's Disease
This study will test the effectiveness of an experimental drug called LY300164 on improving
 Parkinson's disease symptoms, such as movement impairments and tremor, as well as involuntary
 movements produced by long-term treatment with levodopa.

 Patients with relatively advanced (Stage II to IV) Parkinson's disease between 30 and 75
 years of age may be eligible for this 8-week study. Participants will have a complete medical
 history and physical examination, including blood tests and an electrocardiogram, and
 possibly brain magnetic resonance imaging (MRI), CT scan, and chest X-ray.

 Patients will stop taking all anti-parkinsonism medications except levodopa (Sinemet) and the
 experimental drug during the study. For the first 1 to 3 days, patients will be in the
 hospital for a levodopa "dose-finding" procedure. For this study, levodopa is infused through
 a vein for up to 8 hours, with symptoms monitored frequently to determine the doses that will
 produce two results: 1) the dose that is less than what is needed to relieve symptoms, and 2)
 the dose that relieves symptoms, but may produce dyskinesias.

 When these dose rates are determined, patients will begin treatment in one of two groups. One
 will take LY300164 3 times a day, along with levodopa, for 3 weeks. The second group will
 take placebo tablets (a look-alike tablet with no active ingredient) and levodopa on the same
 schedule as the LY300164 group. A brief medical examination and routine blood and urine tests
 will be done weekly. The drug dose will be increased every 3 to 4 days until significant side
 effects occur or the maximal dose is reached. Patients will be closely monitored for 4 hours
 after every increase. At the end of the 3 weeks, or when the maximal dose is reached,
 patients will be readmitted to the hospital for 2 to 3 days for a second levodopa
 dose-finding study, while continuing on LY300164 or placebo. After this test, patients will
 resume taking levodopa and the experimental drug or placebo as before for another 2 weeks.

 At the end of the 2-weeks, the entire procedure will be repeated in both groups, but the
 treatments will be switched-that is, the patients who were taking LY300164 will now take
 placebo, and the patients who took placebo will now take the drug. At the end of the second 3
 weeks, the levodopa infusion procedure will be repeated once more.

 Throughout the study, parkinsonism symptoms and dyskinesias will be evaluated and blood
 samples will be drawn periodically to measure drug levels.
The objective of this study is to evaluate the acute effects of
 alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor blockade on the
 severity of parkinsonian signs and levodopa-associated motor response complications in
 patients with Parkinson's disease. In a controlled proof-of-principle clinical trial,
 efficacy will be assessed through the use of validated motor function scales. Safety will be
 monitored by means of frequent clinical evaluations and laboratory tests.
Males and females between the ages of 30 and 75 are eligible for the study. All will carry
 the diagnosis of idiopathic Parkinson's disease based on the presence of a characteristic
 clinical history and neurological findings. All will have relatively advanced disease
 (Hoehn and Yahr Stages II to IV) with levodopa-associated motor response complications,
 including wearing-off fluctuations and peak-dose dyskinesias.

 No presence or history of any medical condition that can reasonably be expected to subject
 the patient to unwarranted risk.

 No clinically significant laboratory abnormalities including liver enzyme elevations more
 than three times the upper limit of normal, or neutropenia (WBC less than 4000).

 No parkinson's disease patients exhibiting diphasic or end-of-dose dyskinesias or disabling
 dystonia.

 Since LY300164 is an inhibitor of CP4503A4, patients receiving certain drugs metabolized by
 that pathway will not be included.

 No patients who are unable to be treated with levodopa/carbidopa alone or a single,
 relatively short-acting dopamine agonist.

 No patients who require additional treatment with amantadine or other concomitant
 medications.

 No pregnant women or those not practicing effective means of birth control since the
 influence of any investigational compound on the unborn child and reproductive organs is
 unknown.