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

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00286897
• Other study ID #: E2007-E044-301
• Secondary ID: 2005-004314-33
• Status: Completed
• Phase: Phase 3
• First received: February 3, 2006
• Last updated: November 2, 2015
• Start date: February 2006
• Est. completion date: August 2007

Study information

• Verified date: November 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 702
• Est. completion date: August 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• E2007

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Limited

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  Estonia,  France,  Germany,  Hungary,  Israel,  Italy,  Lithuania,  Poland,  Portugal,  Serbia,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient diaries: Change from baseline to final efficacy visit in the mean total daily OFF time (hr).
Secondary	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.