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ACP-103 to Treat Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00086294
Recruitment Status : Completed
First Posted : June 30, 2004
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE June 29, 2004
First Posted Date  ICMJE June 30, 2004
Last Update Posted Date July 2, 2017
Study Start Date  ICMJE June 25, 2004
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE ACP-103 to Treat Parkinson's Disease
Official Title  ICMJE 5HT2A/C Serotonin Blockade in Parkinson's Disease
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.


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.

Detailed Description

Introduction: In Parkinson's disease (PD), levodopa-induced dyskinesias and motor fluctuations are frequent, disabling complications. Therefore, it is imperative to find nondopaminergic approaches to the palliation of parkinsonian signs. Previously, we demonstrated that drugs that block 5HT2A receptors benefit motor dysfunction in parkinsonian animals.

Objective: To test our hypothesis that blockade of serotonin 2A/2C receptors (5HT2A/C) will lessen the severity of parkinsonian signs and levodopa-associated motor response complications in PD patients.

Methods: In a placebo-controlled, proof-of-principle study, the effect of the 5HT2A/C receptor inverse agonist ACP-103 on levodopa induced motor complications and parkinsonian signs will be assessed in up to 20 patients with moderately advanced Parkinson's disease. 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.

Risks and benefits: Risks involved in this study are a minor increase over minimal risks and are deemed reasonable in relation to potential benefits. This investigation should lead to a better understanding of the pathophysiology and treatment of levodopa-induced motor complications in PD.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson's Disease
  • Dyskinesias
Intervention  ICMJE
  • Drug: Intravenous Levodopa
  • Drug: ACP-103
Study Arms  ICMJE Not Provided
Publications * Mizuno Y, Mori H, Kondo T. Parkinson's disease: from etiology to treatment. Intern Med. 1995 Nov;34(11):1045-54. Review.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE November 15, 2007
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Patients who meet all of the following inclusion criteria will be eligible to participate in the study:

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


Patients meeting any of the following exclusion criteria will not be enrolled or will be immediately excluded from the study, as appropriate:

  1. 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;
  2. Patients with clinically significant orthostatic hypotension;
  3. Patient has clinically significant laboratory abnormalities including renal and hepatic functions elevation greater than twice the upper limit of normal;
  4. Patient is unable to be treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist, such as pramipexole or ropinirole;
  5. 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;
    • Dopamine agonists known to have a relatively long half-life: cabergoline and pergolide.
  6. Patient who has not been using or unwilling to continue using an adequate contraceptive method (such as oral contraception, surgical sterilization, IUD, diaphragm in conjunction with spermicidal foam and condom on the male partner, or systemic contraception) for the last 30 days, or is not at least one year post-menopausal (if female);
  7. Patient is pregnant or breastfeeding;
  8. Patient has prior bilateral pallidotomy or other ablative surgeries for treatment of PD;
  9. Patient has cognitive impairment (MMSE less than 24);
  10. Patient has participated in a clinical study with an investigational drug within the last 30 days;
  11. Patient has a condition (such as active drug or alcohol abuse) that, in the opinion of the investigators, would interfere with compliance or safety;
  12. Patient is unwilling to sign an informed consent or to comply with protocol requirements.
  13. Any previous exposure to ACP-103
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00086294
Other Study ID Numbers  ICMJE 040225
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date November 15, 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP