This study will evaluate the effects of an experimental drug called NS2330 on Parkinson's
disease symptoms and on dyskinesias (involuntary movements) that develop as a result of
long-term treatment with levodopa. This drug prevents the neurotransmitter dopamine from
entering nerve cells.
Patients between 18 and 75 years old who have moderately advanced Parkinson's disease and
motor problems resulting from levodopa therapy may be eligible for this 5-week study.
Candidates will have a complete medical history and physical examination with a detailed
neurological evaluation. If needed, some patients will undergo a magnetic resonance imaging
(MRI) or computerized tomography (CT) scan of the brain and a chest X-ray. All patients
will have blood and urine tests and an electrocardiogram (EKG) and will take a written test
for evaluation of depression.
Patients enrolled in the study will, if possible, stop taking all antiparkinson medications
except levodopa (Sinemet) for one month before the study begins and through its duration.
For the first 1 to 3 days, patients will undergo a levodopa "dose-finding" procedure. For
this study, patients will stop taking their usual oral levodopa medicine and instead will
have levodopa infused through a vein for up to 12 hours. During the infusions, the drug
dose will be increased slowly until either 1) parkinsonism symptoms improve, 2) dyskinesias
appear, 3) unacceptable side effects occur, or 4) the maximum study dose is reached.
When the patient's optimal dose is determined, treatment will begin. Patients will take
three pills containing NS2330 or placebo (a look-alike pill with no active ingredient) 3
days a week for up to 5 weeks, in addition to their regular levodopa medication. All
participants will receive placebo at some point in the study; some patients will receive
only placebo throughout the entire 5 weeks.
On treatment days, patients will have a brief medical examination before receiving the drug
and will then be monitored for side effects for about 6 to 8 hours after taking the drug.
At the beginning of weeks 2 and 5, the levodopa infusions will be repeated at the previously
determined optimum rate. Throughout the study, parkinsonism symptoms, dyskinesias and
depression will be evaluated. Blood and urine samples will be collected each week for
standard safety tests, and blood will also be drawn periodically to measure NS2330 levels.
The objective of this study is to evaluate the acute effects of a potent inhibitor of
dopamine reuptake 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, the efficacy of NS2330 will be assessed through the use
of validated motor function scales. Safety will be monitored by means of frequent clinical
evaluations and laboratory tests.
Male and Females are eligible for this study.
Women must be at least one year post-menopausal or using an adequate contraceptive method
for at least one month prior to and during participation in the study.
All will carry the diagnosis of idiopathic Parkinson's disease based on the presence of a
characteristic clinical history and neurologic findings.
All will have relatively advanced disease with levodopa-associated motor response
complications, including wearing-off fluctuations and peak-dose dyskinesias.
The presence or history of any medical condition that can reasonably be expected to
subject the patient to unwarranted risk.
Any clinically significant laboratory abnormalities including liver enzyme elevations more
than twice the upper limit of normal, or neutropenia (wbc less than 4000).
Patients with diphasic or end-of dose dyskinesias or disabling dystonia.
Patients who are unable to be treated with levodopa/carbidopa alone or a single,
relatively short-acting dopamine agonist.
Patients with any form of Parkinsonism other than idiopathic PD or with a diagnosis of
dementia or major psychiatric disorder. Individuals with mild to moderate depression will
be sought for this study, unless their depressive disorder currently requires regular
Patients who are on unacceptable prior/concomitant medications.
Those who are not practicing effective birth control.
Patients with prior bilateral neurosurgical intervention for the treatment of Parkinsonian
symptoms, i.e. deep brain stimulation, pallidotomy, fetal tissue transplantation as well
as patients at risk for symptomatic hypotension, cardiac arrhythmia, and/or myocardial
ischemia secondary to intravenous levodopa challenge or NS2330 therapy.
Patients who have taken an investigational drug within the last two months prior to
Previous participation in any NS 2330 study.