Clinical trial NCT00566462: Assessment of Perampanel (E2007) on Synaptic Dopamine in Mild-moderate PD Patients: A Pilot Study With [^123I]-IBZM SPECT
Official title: Assessment of Perampanel (E2007) on Synaptic Dopamine in Mild-moderate PD Patients: A Pilot Study With [^123I]-IBZM SPECT
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Parkinson's Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2007-12-03
Enrollment: 1
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Change in Striatal [^123I]-Iodobenzamine (IBZM_ Binding Following a Single Dose Carbidopa/Levodopa Challenge for 15-hours at Baseline and Week 4
timeFrame: Baseline and Week 4
Secondary outcomes:
measure: Change in Caudate and Putamen [^123I]-IBZM Binding Following a Single Dose Carbidopa/Levodopa Challenge for 15-hours at Baseline and Week 4
timeFrame: Baseline and Week 4
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Kenneth Marek
state: Connecticut
city: New Haven
country: United States
facility: Molecular NeuroImaging, LLC
state: Connecticut
city: The Woodlands
country: United States
facility: inVentiv
state: Texas
Study officials:
affiliation: Eisai Inc.
name: Patricia Cole, PhD, MD
role: STUDY_DIRECTOR
References: