Assessment of Perampanel (E2007) on Synaptic Dopamine in Mild-moderate PD Patients: A Pilot Study With [^123I]-IBZM SPECT
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: perampanel; placebo
Intervention description: 2 mg/d for 14 days followed by 4 mg/d for 14 days; Matching placebo for for 14 days followed by 4 mg/d for 14 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      This is a two-arm, double-blind, placebo-controlled study.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Male or female patients with idiopathic PD fulfilling the United Kingdom Parkinson's
             Disease Society Brain Bank (UKPDSBB) diagnostic criteria, with a good response to
             levodopa. The requirement in the UKPDSBB Step 2 for prior brain imaging is at the
             discretion of the investigator.

               -  Clinical diagnosis of idiopathic Parkinson's disease (patients must have at least
                  two of the three cardinal symptoms: resting tremor, rigidity, bradykinesia)

               -  Hoehn and Yahr Stage II to IV.

               -  Treatment with monotherapy of levodopa plus an aromatic acid decarboxylase
                  inhibitor (carbidopa). The carbidopa/levodopa medication should be taken at least
                  two times daily (excluding the bedtime/night time dose) up to a maximum of eight
                  doses daily (including the bedtime/night time dose).

               -  Intermittent use of either liquid forms of levodopa or subcutaneous apomorphine
                  is permitted.

               -  Age >30 years of age

               -  Women who are incapable of bearing children (e.g., clinically assessed as
                  infertile, including surgically sterile) or who are practicing effective
                  contraception (e.g., abstinence, intrauterine device or barrier method plus
                  hormonal method).

             Postmenopausal women may be recruited but must be amenorrheic for at least 1 year to
             be considered. Women must have a negative serum beta-human chorionic gondotrophin
             (β-HCG) test at the Screening Visit and a negative urine pregnancy test prior to
             radiotracer administration on the day of each SPECT scanning session. Women must also
             be willing to remain on their current form of contraception for the duration of the
             study.

          2. In the investigator's opinion, patients are able to complete the study and are capable
             of giving full written informed consent.

        EXCLUSION CRITERIA:

        Patients with any one of the following will be excluded:

          1. Inability or unwillingness to undergo SPECT or other study procedures

          2. Pregnant or lactating women

          3. Atypical or drug-induced PD

          4. Current treatment with dopamine agonists, MAO or COMT inhibitors, anticholinergics

          5. Patients with a past (within 1 year) or present history of psychotic symptoms
             requiring antipsychotic treatment. Patients may be taking antidepressant medication,
             however, the dose must be stable for 4 weeks prior to the Baseline Visit. Use of
             antipsychotic medication including clozapine and quetiapine is prohibited, even if the
             indication is for movement disorders.

          6. Current or prior treatment (within 4 weeks prior to Baseline Visit) with pergolide,
             tolcapone, methyldopa, budipine, reserpine, seroquel, or the herbal dopamine agonist,
             Mucuna Pruriens

          7. Patients with current or prior treatment (within 4 weeks prior to the Baseline Visit)
             with medication known to induce the enzyme cytochrome P450 3A4

          8. Use of an investigational product within 4 weeks prior to randomization or patients
             who have participated in a previous study with perampanel

          9. Patients with a past or present history of drug or alcohol abuse as per Diagnostic and
             Statistical Manual - 4th edition (DSM IV) criteria

         10. Dementia (as defined by a MMSE score of ≤ 24) and/or fulfilling the criteria for
             dementia due to PD (as defined by the Diagnostic and Statistical Manual of the
             American Psychiatric Association - 4th Edition)

         11. Clinically significant unstable medical or psychiatric illness

         12. Presence of physical, mental, or social condition that precludes informed consent or
             interferes with careful follow-up

         13. Past (within 1 year) or present history of suicidal ideation or suicide attempts

         14. Elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate
             aminotransferase (AST) ≥ 1.5 times the upper limit of normal (ULN)

         15. Patients with unstable abnormalities of the hepatic, renal, cardiovascular,
             respiratory, gastrointestinal, haematological, endocrine, or metabolic systems that
             might complicate assessment of the tolerability of the study medication

         16. Evidence of significant active hematological disease: white blood cell (WBC) count ≤
             2500/μL; absolute neutrophil count ≤ 1000/μL

         17. Patients with previous stereotactic surgery (eg, pallidotomy) for Parkinson's disease
             or with planned stereotactic surgery during the study period

         18. Patients receiving or planning to receive (within 3 months) deep brain stimulation

         19. Patients with conditions affecting the peripheral or central sensory system unless
             related to Parkinson's disease (such as mild sensory or pain syndromes limited to
             "OFF" periods) that could interfere with the evaluation of any such symptoms caused by
             the study drug

         20. Patients with any condition that would make the patient, in the opinion of the
             investigator, unsuitable for the study

         21. Patients with clinically significant ECG abnormality, including prolonged QTc (defined
             as QTc > 450 msec)