Clinical trial NCT00286897: The Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations
Official title: A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel Group Study of the Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2006-02-06
Enrollment: 702
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: 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.


Eligibility criteria: INCLUSION CRITERIA:

1. Male or female patients with idiopathic PD fulfilling the (UK) Parkinson's disease Society Brain Bank diagnostic criteria, with a good response to levodopa.
2. Patients must have been diagnosed with idiopathic PD at \>= 30 years of age.
3. 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.
4. 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.
5. Patients must rate between II-IV on the Hoehn \& Yahr scale when in an OFF state.
6. 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).
7. 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.
8. 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.
9. 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.

EXCLUSION CRITERIA:

1. Pregnant or lactating women.
2. 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.
3. Fertile men not willing to use reliable contraception and fertile men with partners not willing to use reliable contraception.
4. Patients with a past or present history of drug or alcohol abuse as per DSM IV criteria.
5. 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.
6. Patients with a past (within one year) or present history of suicidal ideation or suicide attempts.
7. 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.
8. Patients with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper normal limit).
9. Patients with current or prior treatment (within 4 weeks prior to the baseline visit) with medication known to induce the enzyme cytochrome P450 3A4.
10. 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.
11. Patients with previous stereotactic surgery (eg pallidotomy) for Parkinson's disease or with planned stereotactic surgery during the study period.
12. Patients receiving or with planned (next 6 months) deep brain stimulation.
13. 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.
14. Patients with clinically significant cognitive impairment (MMSE \<24 and /or fulfilling DSM IV criteria for dementia due to Parkinson's disease).
15. 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.
16. Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study.

Primary outcomes:
measure: Patient diaries: Change from baseline to final efficacy visit in the mean total daily OFF time (hr).
Secondary outcomes:
measure: 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.
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: University Clinic Innsbruck
city: Vienna
country: Austria
facility: Department of Neurology
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Charleroi
country: Belgium
facility: C.H.U.de Charleroi
city: Edegem
country: Belgium
facility: U.Z. Antwerpen
city: Gent
country: Belgium
facility: U.Z. Gent
city: Liege
country: Belgium
facility: C.H.R. de la Citadelle
city: Ottignies
country: Belgium
facility: Hopital St-Pierre
city: Tielt
country: Belgium
facility: St-Andries Ziekenhuis
city: Olomouc
country: Czech Republic
facility: University Hospital
city: Ostrava 10
country: Czech Republic
facility: Pliklinika Modry Pavilon
city: Ostrava
country: Czech Republic
facility: University Hospital
city: Pardubice
country: Czech Republic
facility: Nemocnice Pardubice
city: Plsek
country: Czech Republic
facility: Nemocnice Pisek
city: Plzen
country: Czech Republic
facility: FN Plzen
city: Praha 10
country: Czech Republic
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 2
country: Czech Republic
facility: VFN Praha
city: Parnu
country: Estonia
facility: Parnu Hospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Aix-en-Provence
country: France
facility: Centre Hospitalier du Pays d'Aix
city: Bayonne Cedex
country: France
facility: Service Neurologie
city: Clermont Ferrand
country: France
facility: CHU Gabrief Montpied
city: Colomiers
country: France
facility: Contis, Patrick
city: Lille Cedex
country: France
city: Marseille Cedex 05
country: France
facility: Centre de Pharmacologie Clinique et Evaluation Therapeutique
city: Nantes Cedex 1
country: France
city: Paris Cedex 13
country: France
facility: Hopital de la Pitie Salpetriere
city: Toulouse Cedex 9
country: France
facility: Centre d'Investigation Clinique, Hospital Purpan
city: Beelitz-Heilstatten
country: Germany
facility: Kliniken Beelitz GmbH
city: Berlin
country: Germany
facility: Uni-klinikum Charite, Campus Virchow-klinikum
city: Bochum
country: Germany
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus
city: Gottingen
country: Germany
facility: Neurologische Universitatsklinik
city: Hamburg
country: Germany
facility: Universitatkrankenhaus Hamburg Eppendorf
city: Hanau
country: Germany
city: Hannover
country: Germany
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik
city: Leun-Biskirchen
country: Germany
facility: Gertrudis-Klinik, Parkinson Klinik
city: Lubeck
country: Germany
facility: Universitatsklinik Lubeck Klinik fur Neurologie Ratzeburger Allee 160 D-23538 Lubeck
city: Marburg
country: Germany
facility: Klinik fuer Neurologie
city: Muenchen
country: Germany
facility: Technische Universitaet Muenchen
city: Munchen
country: Germany
facility: LMU Munchen, Neurologische Universitatsklinik
city: Tuebingen
country: Germany
city: Wiesbaden
country: Germany
city: Budapest
country: Hungary
facility: Clinexpert SMO, Budapest
city: Budapest
country: Hungary
facility: St. Imre Hospital
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: Uzsoki Street Hospital
city: Budapest
country: Hungary
facility: Jahn Ferenc Hospital
city: Budapest
country: Hungary
facility: B-A-Z County Hospital
city: Budapest
country: Hungary
city: Gyor
country: Hungary
facility: A Petz Hospital
city: Gyor
country: Hungary
facility: Nyiro Gyula Hospital
city: Miscolc
country: Hungary
facility: Jahn Ferenc Del-Pesti Hospital
city: Haifa
country: Israel
facility: Cham Sheba Medical Center
city: Petach-Tikva
country: Israel
facility: Rabin MC
city: Petach-Tikva
country: Israel
facility: Ichilov Sourasky MC
city: Ramat-Gan
country: Israel
facility: Rambam Healthcare Center
city: Tel Aviv
country: Israel
facility: Carmel Medical Center
city: Zerafin
country: Israel
facility: Assaf Harofe Medical Center
city: Arcugnano
country: Italy
facility: Ospedal Villa Margherita
city: Genova
country: Italy
facility: Universita degli Studi di Genova
city: Grosseto
country: Italy
facility: Ospedale della Misericordia
city: Grosseto
country: Italy
facility: Policlinico Umberto I
city: Lido di Camaiore
country: Italy
facility: Ospedale Versillia
city: Napoli
country: Italy
facility: Universita degli Studi Federico II
city: Pavia
country: Italy
facility: IRCSS Fondazione Casimiro Mondino
city: Pescara
country: Italy
facility: Ospedale Civile di Pescara
city: Roma
country: Italy
facility: Ospedale San Giovanni Battista
city: Roma
country: Italy
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Emergency Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital, Santariskiu Clinic
city: Bialystok
country: Poland
facility: Nzoz Kendrion
city: Bialystok
country: Poland
facility: PSK Klinika Neurologii
city: Gdansk
country: Poland
facility: Klinika Neurologii Doroslych AM
city: Katowice
country: Poland
facility: Centralny Szpital Kliniczny
city: Lublin
country: Poland
facility: WSS im. Kardynala S. Wyszynskiego
city: Lublin
country: Poland
city: Mosina k/Poznania
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska, Gabinet Neur
city: Plock
country: Poland
facility: Specjalistyczna Przychodnia Lekarska
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSwia
city: Warszawa
country: Poland
city: Warszawa
country: Poland
facility: Centrum Leczenia Chorob
city: Coimbra
country: Portugal
facility: Servico de Neurologia
city: Lisboa
country: Portugal
facility: Hospital Santa Maria
city: Porto
country: Portugal
facility: Hospital Santo Antonio
city: Belgrade, Serbia and Montenegro
country: Serbia
facility: Clinic of Neurology and Psychiatry
city: Belgrade, Serbia and Montenegro
country: Serbia
facility: Clinic of Neurology
city: Belgrade, Serbia and Montenegro
country: Serbia
facility: Institute of Neurology
city: Bloemfontein 9301
country: South Africa
facility: Rosepark Hospital
city: Bloemfontein
country: South Africa
facility: 407 Medi Clinic
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Cape Town
country: South Africa
facility: Christian Barnard Memorial Hospital
city: Cape Town
country: South Africa
facility: 406 Claremont Hospital
city: Morningside, Johannesburg
country: South Africa
city: Parow
country: South Africa
facility: Panorama Medi-Clinic
city: Pretoria
country: South Africa
facility: Wilgers Medical Centre
city: Sunninghill, Johannesburg
country: South Africa
facility: Sunninghill Hospital
city: Umhlanga
country: South Africa
facility: Umhlanga Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Barcelona
country: Spain
facility: Hospital de sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital del Mar, Servei de Neurologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Karlstad
country: Sweden
facility: Praktiken Ankaret
city: Stockholm
country: Sweden
facility: St Gorans Sjukhus
city: Blackpool
country: United Kingdom
facility: Bupa Flyde Coast Hospital
city: Chertsey
country: United Kingdom
facility: North Surrey Primary Care Trust
city: Clwyd
country: United Kingdom
facility: District General Hospital NHS Trust
city: Crumpsall
country: United Kingdom
facility: North Manchester General Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Eisai Limited
name: Alessia Nicotra, MD, PhD, DIC
role: STUDY_DIRECTOR
References: