This study will evaluate the effects of an experimental drug called EMD 128130 on
Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a
result of long-term treatment with levodopa. EMD 128130 inhibits the function of serotonin,
a chemical messenger thought to regulate dopamine release, and thus affect Parkinson's
Patients with relatively advanced Parkinson's disease between 30 and 80 years of age may be
eligible for this 3-phase study.
- Phase 1 - Baseline Evaluation
Participants will have a medical history, physical examination, detailed neurologic
evaluation, routine blood tests, urinalysis and an electrocardiogram. A chest X-ray and MRI
or CT scan of the brain will be done if needed. In addition, an ACTH stimulation test will
be done before and at the end of the study. For this test, a hormone called ACTH is
injected into a vein. A small amount of blood is drawn before the injection and 30 and 60
minutes afterwards to measure levels of another hormone called cortisol. After these tests
are completed, patients will, if possible, stop taking all antiparkinsonian medications
except levodopa (Sinemet) for one month before the study begins and throughout its duration.
- Phase 2 - Levodopa and Apomorphine Dose Finding
For 1 to 3 days, patients will be admitted to the NIH Clinical center to undergo a levodopa
and apomorphine (a dopamine agonist) "dose-finding" procedure. For this procedure, patients
will stop taking Sinemet and instead will have levodopa, and subsequently apomorphine,
infused through a vein. During the infusions, the drug dose will be increased slowly until
either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the
maximum study dose is reached. Symptoms will be monitored frequently to find two infusion
rates: 1) one that is less than what is needed to relieve symptoms, and 2) one that relieves
symptoms but may produce dyskinesias.
- Phase 3 - Active Study
Patients will begin the treatment phase within 3 months of the dose-finding phase. After a
brief physical examination, routine blood tests, and evaluation of parkinsonism symptoms,
patients will begin taking either EMD 128130 tablets or capsules or a placebo (a look-alike
pill with no active ingredient) twice a day, along with Sinemet, for 3 weeks. All
participants will receive placebo at least 1 week during the study, and about four patients,
selected at random, will receive only placebo the entire 3 weeks. Levodopa and apomorphine
infusions will be repeated at the end of weeks 1, 2 and 3 of Phase 3. The procedure for
the infusions will be the same as in the dose-finding phase.
Throughout the study, parkinsonian symptoms and dyskinesias will be assessed and blood
samples will be drawn periodically to measure drug levels. Patients will return for a
follow-up evaluation 2 weeks after the end of the study.
The objective of this study is to evaluate the acute effects of a selective agonist of
serotonin 5-HT1A receptors on the severity of parkinsonian signs and levodopa-associated
motor response complications in patients with moderately advanced Parkinson's disease. In a
controlled proof-of-principle clinical trial, the efficacy of EMD 128130 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 30-80.
Females must be either at least one year post-menopausal, or using an adequate
contraceptive method for at least one month prior to and during participation in this
Patients will carry the diagnosis of idiopathic Parkinson's disease based on the presence
of a characteristic clinical history and neurologic findings.
Patients will have relatively advanced disease with levodopa-associated motor response
complications, including peak-dose dyskinesias and wearing-off fluctuations.
Patients with the presence or history of any medical condition that can reasonably be
expected to subject the patient to unwarranted risk will be excluded.
Patients with clinically significant laboratory abnormalities including liver enzyme
elevations more than two times the upper limit of normal will be excluded.
Patients who are unable to be treated with levodopa/carbidopa alone or with a single,
relatively short-acting dopamine agonist will be excluded.
Patients with a form of parkinsonism other than idiopathic PD will be excluded.
Patients with unacceptable prior/concomitant medications will be excluded.
No pregnant women. Female and male patients must be practicing effective means of birth
Patients with prior bilateral surgical intervention for the treatment of parkinsonian
symptoms, i.e. deep brain stimulation, pallidotomy, fetal tissue transplantation will be
Patients at risk for hypotension, cardiac arrhythmia, and/or myocardial ischemia secondary
to intravenous levodopa challenge will not be eligible.
Patients with cognitive impairment (MMSE less than 25) will not be eligible.
Patients with subnormal serum cortisol responses to acute ACTH stimulation will be