ACP-103 to Treat Parkinson's Disease

NCT00086294 | Completed Phase 2

• 2 other identifiers: 04022504-N-0225
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effects of an experimental drug called ACP-103 on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term levodopa treatment. ACP-103 changes the spread of certain brain signals that are affected in patients with Parkinson's disease. Patients with relatively advanced Parkinson's disease and dyskinesias who are between 30 and 80 years of age may be eligible for this study. Candidates are screened with a complete medical history and physical examination, neurological evaluation, blood and urine tests, and electrocardiogram (ECG). A brain magnetic resonance imaging (MRI) scan, CT scan, and chest x-ray may be done if medically indicated. Patients enrolled in the study will, if possible, stop taking all antiparkinsonian medications for one month (2 months for Selegiline) before the study begins and throughout its duration. Exceptions are Sinemet (levodopa/carbidopa), Mirapex (pramipexole) and Requip (ropinirole). Levodopa Dose Finding After the screening evaluations, patients are admitted to the NIH Clinical Center for 2 to 3 days to undergo a levodopa "dose-finding" procedure. For this test, patients stop taking Sinemet and instead have levodopa infused through a vein. During the infusion, the drug dose is increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Side effects are monitored closely during the infusions, and parkinsonian symptoms are evaluated frequently during and after the infusions. The infusions usually begin early in the morning and continue until evening. Once the infusion is finished, patients resume taking their regular oral Sinemet dose. The infusions are repeated once a week during 1-day inpatient evaluations. Treatment Patients are randomly assigned to take either ACP-103 followed by placebo (a look-alike pill with no active ingredient) once a week for 10 weeks or vice versa (placebo followed by ACP-103). Patients are admitted to the Clinical Center for each dose. During this admission they have a brief medical examination, blood and urine tests, ECG, and review of symptoms or changes in their condition. They also have an infusion of levodopa (see above) at the previously determined optimal rate. Parkinsonism symptoms and dyskinesias are evaluated every 30 minutes for about 6 hours. At the end of the infusions and ratings, patients are discharged home with their regular Parkinson's medications until the following visit. Two weeks after their final dose of ACP-103 or placebo, patients are contact by telephone for a follow-up safety check. At that time, the investigator may ask the patient to return to the clinic for closer evaluation.

Conditions

Parkinson's Disease; Dyskinesias

Keywords

Non-Dopaminergic; Dyskinesias; Fluctuations; Inverse Agonist; ACP-103; Parkinson Disease; PD

Interventions

Intravenous Levodopa DRUG

ACP-103 DRUG

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is between the ages of 30 and 80 (inclusive);
• Patient has been diagnosed with idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurological findings;
• Patient has relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations;
• Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.

You may not qualify if:

• Patient has a history of any medical condition that can reasonably be expected to subject the patient to unwarranted risk, including bronchospasm or lung disease, renal and hepatic disease, clinically significant cardiac arrhythmias and/or myocardial ischemia;
• Patients with clinically significant orthostatic hypotension;
• Patient has clinically significant laboratory abnormalities including renal and hepatic functions elevation greater than twice the upper limit of normal;
• Patient is unable to be treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist, such as pramipexole or ropinirole;
• Patient is taking a prohibited concomitant medication as listed below:
• The following medications are forbidden for at least one month prior to randomization and during the course of the study:
• Anticoagulants: etomidate, erythromycin, oral azole antifungals, cyclosporine, cisapride, astemizole;
• NMDA antagonists: e.g. amantadine, budipine, memantine, remacemide, dextromethorphan;
• Any other investigational drug;
• Drugs which are not used primarily to treat Parkinson's disease but which may modify parkinsonian symptoms: neuroleptics, metoclopramide, compazine, beta blockers;
• Drugs with significant muscarinic receptor antagonist activity: Cogentin, Akineton, Artane, Ditropan, Detrol, Elavil, Anafranil, Norpramine, Sinequan, Tofranil, and Pamelor;
• Drugs known to improve dyskinesias: amantadine, dextromethorphan, beta-blockers, fluoxitene, clozapine, quetiapine, olanzapine, buspirone, other anxiolytics, antipsychotics, cannabinoid receptor antagonists, adenosine A2a antagonist;
• Drugs known to exacerbate dyskinesias: sodium valproate, CNS stimulants;
• Drugs known to have 5HT receptor affinity: ritanserin, sumatriptan
• Drugs known to interact with serotonergic mechanisms excluding 5HT3 receptor based antiemetics;

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Mizuno Y, Mori H, Kondo T. Parkinson's disease: from etiology to treatment. Intern Med. 1995 Nov;34(11):1045-54. doi: 10.2169/internalmedicine.34.1045.

  PMID: 8774962 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Interventions

pimavanserin

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 29, 2004
• First Posted: June 30, 2004
• Study Start: June 25, 2004
• Study Completion: November 15, 2007
• Last Updated: July 2, 2017

Record last verified: 2007-11-15

Locations

US (1)