The Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations

NCT00286897 | Completed Phase 3

• 2 other identifiers: E2007-E044-3012005-004314-33
• Study Type: interventional
• Target: 702
• Locations: 15 countries
• Sites: 107

Brief Summary

Patients will be randomised to receive either placebo or the study drug for a period of 30 weeks, in addition to their standard Parkinsonian medications. During the first 8 weeks, the patient's levodopa doses may be adjusted if necessary by the investigator. For the remainder of the 22 weeks, all medications should be kept stable. Patients will be required to attend the clinic twice during the screening period and then a further 8 times during the treatment period. They will be required to complete home diaries where they will record their motor function. In addition, their doctor will assess their Parkinson's disease during the clinic visits. There will also be blood draws for safety and pharmacokinetic and pharmacogenomics evaluation. Following the treatment and assessment period, they will return to the clinic one month later for follow up.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Patient diaries: Change from baseline to final efficacy visit in the mean total daily OFF time (hr).

Secondary Outcomes (1)

• Change from baseline on average OFF time over total treatment period; UPDRS Part II: OFF state; UPDRS Part III: ON state; change from baseline to final efficacy visit in mean total daily ON time w/o dyskinesias or with no troublesome dyskinesias.

Interventions

E2007 DRUG

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with idiopathic PD fulfilling the (UK) Parkinson's disease Society Brain Bank diagnostic criteria, with a good response to levodopa.
• Patients must have been diagnosed with idiopathic PD at \>= 30 years of age.
• Patients must have predictable motor fluctuations of the wearing OFF type with the presence of at least 2 hours of OFF time during the waking day (excluding the morning OFF time) as evidenced by diary cards completed at screening and confirmed by diary data collected at the baseline visit.
• Before patients are randomised they must be able to show that they are able to accurately complete the diary cards. During the diary-training period at the initial screening visit there must be diary evidence of at least one transition of OFF to ON or from ON to OFF and patients must show 75% concordance with Investigator's completion of the diary card.
• Patients must rate between II-IV on the Hoehn \& Yahr scale when in an OFF state.
• Patients must be taking optimised levodopa therapy (according to investigator's opinion) at least 3 times during the waking day (not including bedtime/night time dose) up to a maximum of 8 doses daily (includes bedtime/night time dose).
• Patients who are treated with dopamine agonists, COMT inhibitors or MAOB inhibitors and other anti-PD drugs must be on optimised and stable doses for at least 4 weeks prior to initial screening visit and must remain stable throughout the study. Only levodopa dosage can be adjusted downwards in the first 8 weeks of the double-blind treatment phase.
• In the Investigator's opinion patients must be able to distinguish their own motor states and the absence or presence of troublesome or non-troublesome dyskinesias.
• In the Investigator's opinion patients are able to complete the study including the completion of the home diary cards and capable of giving full written informed consent.

You may not qualify if:

• Pregnant or lactating women.
• Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g., abstinence, IUD or barrier method plus hormonal method). These patients must have a negative serum B-HCG test at the initial screening visit (Visit 1), and a negative urine pregnancy test at the Baseline visit (Visit 3). 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 as determined by the investigator.
• Fertile men not willing to use reliable contraception and fertile men with partners not willing to use reliable contraception.
• Patients with a past or present history of drug or alcohol abuse as per DSM IV criteria.
• 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 be stable for 4 weeks prior to the baseline visit. Use of anti-psychotic medication including clozapine and quetiapine is prohibited even if the indication is for movement disorders.
• Patients with a past (within one year) or present history of suicidal ideation or suicide attempts.
• 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.
• Current or prior treatment (within 4 weeks prior to the baseline visit) with tolcapone, methyldopa, budipine, reserpine, seroquel or intermittent use of either liquid forms of levodopa or subcutaneous apomorphine.
• Patients with previous stereotactic surgery (eg pallidotomy) for Parkinson's disease or with planned stereotactic surgery during the study period.
• Patients receiving or with planned (next 6 months) deep brain stimulation.
• Patients who have received an investigational product within 4 weeks prior to the screening visit or patients that have participated in a previous study with E2007.
• Patients with clinically significant cognitive impairment (MMSE \<24 and /or fulfilling DSM IV criteria for dementia due to Parkinson's disease).
• 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.

Sponsors & Collaborators

• Eisai Limited: lead

Study Sites (118)

University Clinic Innsbruck

Innsbruck, 6020, Austria

Location

Department of Neurology

Vienna, Austria

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

C.H.U.de Charleroi

Charleroi, 6000, Belgium

Location

U.Z. Antwerpen

Edegem, 2650, Belgium

Location

U.Z. Gent

Ghent, 9000, Belgium

Location

C.H.R. de la Citadelle

Liège, 4000, Belgium

Location

Hopital St-Pierre

Ottignies, 1340, Belgium

Location

St-Andries Ziekenhuis

Tielt, 8700, Belgium

Location

University Hospital

Olomouc, 77520, Czechia

Location

University Hospital

Ostrava, 70852, Czechia

Location

Pliklinika Modry Pavilon

Ostrava, 71000, Czechia

Location

Nemocnice Pardubice

Pardubice, 53203, Czechia

Location

FN Plzen

Pilsen, 30460, Czechia

Location

Nemocnice Pisek

Plsek, 39723, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

VFN Praha

Prague, 12800, Czechia

Location

Parnu Hospital

Pärnu, 80010, Estonia

Location

West Tallinn Central Hospital

Tallinn, 10617, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

Centre Hospitalier du Pays d'Aix

Aix-en-Provence, 13090, France

Location

Service Neurologie

Bayonne, 64100, France

Location

CHU Gabrief Montpied

Clermont-Ferrand, 69003, France

Location

Contis, Patrick

Colomiers, 31770, France

Location

Unknown Facility

Lille, France

Location

Centre de Pharmacologie Clinique et Evaluation Therapeutique

Marseille, 13385, France

Location

Unknown Facility

Nantes, France

Location

Hopital de la Pitie Salpetriere

Paris, 75013, France

Location

Centre d'Investigation Clinique, Hospital Purpan

Toulouse, 31059, France

Location

Kliniken Beelitz GmbH

Beelitz-Heilstätten, Germany

Location

Uni-klinikum Charite, Campus Virchow-klinikum

Berlin, 13353, Germany

Location

Unknown Facility

Bochum, Germany

Location

Universitaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Neurologische Universitatsklinik

Göttingen, Germany

Location

Universitatkrankenhaus Hamburg Eppendorf

Hamburg, D 20246, Germany

Location

Unknown Facility

Hanau, Germany

Location

Unknown Facility

Hanover, Germany

Location

Paracelsus-Elena-Klinik

Kassel, 34128, Germany

Location

Gertrudis-Klinik, Parkinson Klinik

Leun-Biskirchen, Germany

Location

Universitatsklinik Lubeck Klinik fur Neurologie Ratzeburger Allee 160 D-23538 Lubeck

Lübeck, 23538, Germany

Location

Klinik fuer Neurologie

Marburg, 35033, Germany

Location

Technische Universitaet Muenchen

München, 81675, Germany

Location

LMU Munchen, Neurologische Universitatsklinik

München, Germany

Location

Unknown Facility

Tübingen, Germany

Location

Unknown Facility

Wiesbaden, 65191, Germany

Location

Clinexpert SMO, Budapest

Budapest, 1091, Hungary

Location

St. Imre Hospital

Budapest, 1115, Hungary

Location

Semmelweis University

Budapest, 1145, Hungary

Location

Uzsoki Street Hospital

Budapest, 1145, Hungary

Location

Jahn Ferenc Hospital

Budapest, 1204, Hungary

Location

B-A-Z County Hospital

Budapest, 3501, Hungary

Location

Unknown Facility

Budapest, Hungary

Location

A Petz Hospital

Győr, 9024, Hungary

Location

Nyiro Gyula Hospital

Győr, Hungary

Location

Jahn Ferenc Del-Pesti Hospital

Miscolc, 3501, Hungary

Location

Cham Sheba Medical Center

Haifa, 52621, Israel

Location

Rabin MC

Petah Tikva, 49372, Israel

Location

Ichilov Sourasky MC

Petah Tikva, 64239, Israel

Location

Rambam Healthcare Center

Ramat Gan, 52621, Israel

Location

Carmel Medical Center

Tel Aviv, Israel

Location

Assaf Harofe Medical Center

Zerafin, 70300, Israel

Location

Ospedal Villa Margherita

Arcugnano, 36057, Italy

Location

Universita degli Studi di Genova

Genova, 16132, Italy

Location

Ospedale della Misericordia

Grosseto, 58100, Italy

Location

Policlinico Umberto I

Grosseto, 58100, Italy

Location

Ospedale Versillia

Lido di Camaiore, 55043, Italy

Location

Universita degli Studi Federico II

Napoli, 80131, Italy

Location

IRCSS Fondazione Casimiro Mondino

Pavia, 27100, Italy

Location

Ospedale Civile di Pescara

Pescara, 65124, Italy

Location

Ospedale San Giovanni Battista

Roma, 00148, Italy

Location

Unknown Facility

Roma, Italy

Location

Kaunas Medical University Hospital

Kaunas, LT5009, Lithuania

Location

Vilnius University Emergency Hospital

Vilnius, 04130, Lithuania

Location

Vilnius University Hospital, Santariskiu Clinic

Vilnius, 2600, Lithuania

Location

Nzoz Kendrion

Bialystok, 15420, Poland

Location

PSK Klinika Neurologii

Bialystok, Poland

Location

Klinika Neurologii Doroslych AM

Gdansk, 80211, Poland

Location

Centralny Szpital Kliniczny

Katowice, 40752, Poland

Location

WSS im. Kardynala S. Wyszynskiego

Lublin, 20718, Poland

Location

Unknown Facility

Lublin, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska, Gabinet Neur

Mosina k/Poznania, 62050, Poland

Location

Specjalistyczna Przychodnia Lekarska

Płock, 09402, Poland

Location

Centralny Szpital Kliniczny MSwia

Warsaw, 02507, Poland

Location

Unknown Facility

Warsaw, 02507, Poland

Location

Centrum Leczenia Chorob

Warsaw, 02777, Poland

Location

Servico de Neurologia

Coimbra, 3000-075, Portugal

Location

Hospital Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital Santo Antonio

Porto, 4099-001, Portugal

Location

Clinic of Neurology and Psychiatry

Belgrade, Serbia and Montenegro, Serbia

Location

Clinic of Neurology

Belgrade, Serbia and Montenegro, Serbia

Location

Institute of Neurology

Belgrade, Serbia and Montenegro, Serbia

Location

407 Medi Clinic

Bloemfontein, 9301, South Africa

Location

Rosepark Hospital

Bloemfontein, South Africa

Location

Groote Schuur Hospital

Cape Town, 7925, South Africa

Location

Christian Barnard Memorial Hospital

Cape Town, 8001, South Africa

Location

406 Claremont Hospital

Cape Town, South Africa

Location

Unknown Facility

Morningside, Johannesburg, 2196, South Africa

Location

Panorama Medi-Clinic

Parow, 7550, South Africa

Location

Wilgers Medical Centre

Pretoria, 0041, South Africa

Location

Sunninghill Hospital

Sunninghill, Johannesburg, 2052, South Africa

Location

Umhlanga Hospital

Umhlanga, 4321, South Africa

Location

Hospital Clinic I Provincial

Barcelona, 08036, Spain

Location

Hospital de sant Pau

Barcelona, 8025, Spain

Location

Hospital Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital del Mar, Servei de Neurologia

Barcelona, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Puerta de Hierro

Madrid, 28035, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Praktiken Ankaret

Karlstad, 65224, Sweden

Location

St Gorans Sjukhus

Stockholm, 11281, Sweden

Location

Bupa Flyde Coast Hospital

Blackpool, FY38BP, United Kingdom

Location

North Surrey Primary Care Trust

Chertsey, KT160QA, United Kingdom

Location

District General Hospital NHS Trust

Clwyd, LL185UJ, United Kingdom

Location

North Manchester General Hospital

Crumpsall, M85RB, United Kingdom

Location

Royal Free Hospital

London, NW32QG, United Kingdom

Location

University College Hospital

London, W1N8AA, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S102FJ, United Kingdom

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, MD, PhD, DIC

  Eisai Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 3, 2006
• First Posted: February 6, 2006
• Study Start: February 1, 2006
• Primary Completion: June 1, 2007
• Study Completion: August 1, 2007
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

BE (7); IL (6); SE (2); GB (7); AU (2); PT (3); PL (11); ZA (10); HU (10); LI (3); ES (3); DE (16); CZ (8); FR (9); IT (10)