Long-Term Safety, Tolerability and Efficacy in Perampanel Treated Parkinson's Disease Patients With Motor Fluctuations

A 48-month Open Label Multi-centered Extension Study to Evaluate the Long-term Safety, Tolerability and Efficacy of E2007 in Patients With Parkinson's Disease With "Wearing Off" Motor Fluctuations and "on" Period Dyskinesias

A 48-month open label multi-centered extension study to evaluate the long-term safety, tolerability and efficacy of E2007 in patients with Parkinson's Disease with "wearing off" motor fluctuations and "on" period Dyskinesias.

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Perampanel

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients enrolled in Study E2007-E044-204 and who either completed 12 weeks of study drug treatment or who withdrew from the study due to lack of efficacy.

Exclusion Criteria:

• Pregnant or lactating women.
• Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g. abstinence, IUD-intrauterine device, or barrier method plus hormonal method). These patients must also be willing to remain on their current form of contraception for the duration of the study. Postmenopausal women may be recruited but must be amenorrhoeic for at least 1 year to be considered of non-child bearing potential.
• Fertile men not willing to use reliable contraception and fertile men with partners not willing to use reliable contraception. These patients and their partners must also be willing to remain using reliable contraception for the duration of the study.
• Patients with a past or present history of drug or alcohol abuse.
• Patients with a past (within one year) or present history of psychotic symptoms requiring antipsychotic treatment. Patients may be taking anti-depressant medication, however the dose must have been kept stable for at least 8 weeks prior to baseline visit.
• Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastro-intestinal, haematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication.
• Patients with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper normal limit).
• Patients with current or prior treatment (within 4 weeks prior to the Baseline visit) with medication known to induce the enzyme cytochrome P450 3A4 including but not limited to; carbamazepine; dexamethasone; ethosuximide; phenobarbital; phenytoin; primidone; rifabutin; rifampicin; and St John's Wort.
• Current or prior treatment (within 4 weeks prior to baseline visit) with methyldopa, budipine, reserpine or intermittent use of liquid forms of levodopa or as needed (prn) apo-morphine.
• Patients with previous stereotactic surgery (e.g. pallidotomy) for Parkinson's disease or who are likely to undergo surgery for Parkinson's disease while participating in this study.
• Patients receiving deep brain stimulation (DBS) or who are likely to undergo DBS for Parkinson's disease while participating in the extension study.
• Patients with clinically significant cognitive impairment (mini-mental state examination (MMSE) <24 and /or fulfilling diagnostic and statistical manual of mental disorders (DSM IV) criteria for dementia due to Parkinson's disease).
• Patients with conditions affecting the peripheral or central sensory system.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Perampanel (1-4 mg); Subjects entered this open-label extension study from the double-blind core study (E2007-E044-204), and dosed placebo or perampanel. Subjects started this open-label extension study on perampanel 1 mg once daily for two weeks, followed by 2 mg once daily for two weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner.

Drug: Perampanel; 1mg once daily for two weeks, followed by 2mg once daily for 2 weeks; if they did not tolerate the 1 mg dose, subjects were withdrawn from the study. Subjects could be up-titrated to 3 or 4 mg in a sequential manner. Subjects could be down-titrated at any time to either 3, 2 or 1 mg in a sequential manner.; Other Names: E2007

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study	OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. This outcome measure was based on data collected through use of a patient diary.	Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study	ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. This outcome measure was based on data collected through use of a patient diary.	Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study	Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. Part III assesses motor activity, based on 14 items, such as gait, facial expression, and rigidity. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. Range of possible total scores, 0 to 56. ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor.	Baseline, Week 0, Week 12, Week 24, Week 36, Week 52, Week 78, Week 104, Week 130, Week 156

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (ESTIMATE): July 6, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): July 9, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: E2007-E044-205; 2004-000361-35 (EUDRACT_NUMBER)