ACP-103 to Treat Parkinson's Disease
Condition: Parkinson's Disease; Dyskinesias
MeSH terms: Parkinson Disease; Dyskinesias
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Intravenous Levodopa; ACP-103
Intervention type(s): Drug; Drug
Intervention MeSH terms: Levodopa; Pimavanserin
Primary purpose: Treatment
Keywords: Non-Dopaminergic; Dyskinesias; Fluctuations; Inverse Agonist; ACP-103; Parkinson Disease; PD