The Effect Of E2007 On Pharmacodynamic Responses To Levodopa Among Patients With Parkinson's Disease Who Experience Dyskinesia And Motor Fluctuations

NCT00451633 | Withdrawn Phase 2

• 1 other identifier: E2007-E044-213
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 5

Brief Summary

A randomized, double blind, placebo-controlled study employing a mixed parallel group and fixed sequence cross-over design. Patients will be randomized to one of two treatment groups ('E2007' or 'Placebo') in a 1:1 ratio and receive investigational drug treatment concomitant with their standard individualized anti-Parkinsonian therapy for a total of six weeks. Investigational drug treatment for patients in the E2007 treatment group will be started 2 mg E2007 o.d. but will be escalated to 4 mg E2007 o.d. after three weeks.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Levodopa pharmacokinetics will be assessed after each levodopa challenge. Blood samples for measurement of levodopa plasma

• concentrations will be taken before and after levodopa dosing or until a full 'off' state is reached if earlier than 5 h.

Secondary Outcomes (1)

• Pharmacodynamic assessments of dyskinesias and motor function; Goetz/Rush dyskinesia rating scale; modified abnormal involuntary movement scale (AIMS), and Unified Parkinson's disease rating scale motor examination sub-scale (UPDRS Part 3) scores.

Interventions

E2007 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:

• Men or women aged between 30 and 80 years, inclusive.
• A diagnosis of idiopathic Parkinson's disease. Patients should fulfill the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (Queen Square criteria) and have a rating of 2.4 on the Hoehn \&Yahr scale when in an "off" state.
• Receiving a regimen of anti-Parkinsonian treatments that has been optimized (according to the Investigator's opinion) and has been stable for at least four weeks before baseline. The regimen is not considered to be stable if 'as required' or 'on demand' dosing is routinely used or there is regular use of apomorphine or liquid forms of levodopa.
• Taking levodopa at least three times during the waking day (not including bedtime or nighttime doses) and with a demonstrable response to each levodopa dose.
• Consistently experiencing clinically-relevant, peak-effect levodopa-induced dyskinesias during the 'on' period following the morning dose of levodopa. Patients should:
• score .2 on Questions 32 and 33 of the full UPDRS at screening.
• have at least 3 h of 'on' time with dyskinesias on average per day recorded in the patient diary at baseline, of which 1 h is within the 4 h following the first morning dose of levodopa.
• Consistently experiencing end-of-dose motor fluctuations. Patients should:
• score .1 on Question 39 of the full UPDRS at screening.
• have at least 1.5 h of 'off' time on average per day recorded in the patient diary at baseline.
• Capable of adhering to the protocol requirements and providing written informed consent.

You may not qualify if:

• A history of drug or alcohol abuse.
• A history of suicide attempt or suicidal ideation within the past year.
• Receiving antipsychotic treatment or a history of psychotic symptoms requiring antipsychotic treatment within the past year. Patients taking anti-depressant medications can enter the study providing the regimen is stable.
• Receiving treatment with monoamine oxidase (MAO)-B inhibitors (e.g., selegiline, rasagiline).
• Receiving treatment with medication known to induce CYP3A4 activity.
• Receiving treatment with medications believed to have an effect on levodopa-induced dyskinesias (e.g., amantadine, dextromethorphan, clozapine, olanzapine, quetiapine).
• Receiving treatment with medications known to exacerbate dyskinesias (eg, sodium valproate, CNS stimulants).
• Failing to respond to the specified levodopa challenge, or where the levodopa challenge is not medically appropriate.
• Experiencing dyskinesias unrelated to peak levodopa effect (e.g., "D-I-D" pattern).
• Previous stereotactic surgery (e.g., pallidotomy, subthalamic nucleus deep brain stimulation) for Parkinson's disease.
• Having received an investigational product within the four weeks leading up to Screening or having participated in a previous study with E2007.
• Clinically significant cognitive impairment (mini-mental state examination \[MMSE\] \<26 or fulfilling DSM IV criteria for dementia due to Parkinson's disease).
• Active hepatic disease, significantly reduced hepatic function or significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper limit of the normal range).
• Clinically significant ECG abnormalities, including prolonged QT interval (defined as QTc .450 msec).
• Narrow-angle glaucoma.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (5)

St. Josef Hospital

Bochum, 44791, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Neurologische Universitatsklinik Marburg

Marburg, D-35039, Germany

Location

CESI - Centro Ricerche Cliniche - Fondazione Universita degli Studi

Chieti, 66013, Italy

Location

U.O. Riabilitazione Neuromotoria, IRCCS San Raffaele Pisana

Roma, 00163, Italy

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

perampanel

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Alessia Nicotra, M.D., Ph.D.

  Eisai Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2007
• First Posted: March 23, 2007
• Study Start: March 1, 2007
• Last Updated: October 31, 2013

Record last verified: 2013-10

Locations

IT (2); DE (3)