A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Safety, Tolerability and Efficacy of E2007 in Parkinson's Disease Patients With "Wearing Off" Motor Fluctuations and "On" Period Dyskinesias

NCT ID: NCT01172379

Last Updated: 2014-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31

Brief Summary

The purpose of this study is to investigate the safety, tolerability and efficacy of E2007 in Parkinson's Disease patients who have "wearing off" motor fluctuations and "on" period dyskenisias.

Detailed Description

This is a randomised, double-blind, placebo-controlled, dose-ranging multicentre study with parallel groups. Patients will be equally randomized to receive 0.5 mg, 1 mg or 2 mg of E2007 or matching placebo for 12 weeks (84 days) in addition to their stable antiparkinsonian treatment. The study will involve two overnight in-patient stays. The first of these will be for 2 nights and 3 days and the second will be for 1 night and 2 days. The remainder of the study will be conducted on an outpatient basis.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Experimental 1

Group Type: EXPERIMENTAL

E2007

Intervention Type: DRUG

Experimental 1 Drug: E2007

0.5 mg 1 tablet per day

Experimental 2

Group Type: EXPERIMENTAL

E2007

Intervention Type: DRUG

Experimental 2 Drug: E2007

1.0 mg 1 tablet per day

Experimental 3

Group Type: EXPERIMENTAL

E2007

Intervention Type: DRUG

Drug: E2007

2.0 mg 1 tablet per day

Placebo Comparator

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: OTHER

Placebo 1 tablet per day

Interventions

E2007

Experimental 1 Drug: E2007

0.5 mg 1 tablet per day

Intervention Type: DRUG

E2007

Experimental 2 Drug: E2007

1.0 mg 1 tablet per day

Intervention Type: DRUG

E2007

Drug: E2007

2.0 mg 1 tablet per day

Intervention Type: DRUG

Placebo Comparator

Placebo 1 tablet per day

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male or female patients with idiopathic PD fulfilling the Queen Square Brain Bank diagnostic criteria, with good response to levodopa.

2. Patients must be aged 30-75 inclusive. Patients aged between 76-80 (inclusive) may be enrolled with the prior agreement of the Study Medical Monitor.

3. Patients must have motor fluctuations of the wearing "off" type with the presence of at least two and half hours of "off" time during the waking day and at least 90 minutes of "off" time during the eight hour period following the morning dose of levodopa each per day as evidenced by history at Screening and confirmed by diary data collected between Screening and Baseline.

4. Patients must have clinically relevant dyskinesias during the "on" period following each morning dose of his/her current medication.

5. Patients must rate between II-IV on the Hoehn and Yahr scale when in an "off" state.

6. Patients must be taking levodopa at least three times daily.

7. Patients must have been on a fixed dose of any treatments for PD for at least 4 weeks prior to the Baseline Visit.

8. In the Investigator's opinion patients must be able to distinguish their own motor states and the absence or presence of dyskinesias.

9. Patients must be capable of giving full written informed consent.

10. In the Investigator's opinion patients must be of capable of completing patient diary cards according to instructions.

11. In the Investigator's opinion patients who are good candidates and able to complete the study.

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 and a negative urine pregnancy test at the Baseline Visit. 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.

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.

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 8 weeks prior to the Baseline Visit.

6. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory, gastrointestinal, haematological, endocrine or metabolic systems which might complicate assessment of the tolerability of the study medication.

7. Patients with significantly elevated liver enzymes (abnormal bilirubin or seum transaminase levels of more than 1.5 times the upper normal limit).

8. Patients currently receiving treatment with medication that could significantly interfere with gastric absorption.

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 including but not limited to: carbamazepine; dexamethasone; ethosuximide; phenobarbital; phenytoin; primidone; rifabutin; rifampacin; and St. John's Wort.

10. Current or prior treatment (within 4 weeks prior to Baseline Visit) with methyldopa, budipine, reserpine or intermittent use of liquid forms of levodopa or apomorphine.

11. Patients with previous stereotactic surgery (e.g., pallidotomy) for Parkinson's disease.

12. Patients receiving deep brain stimulation.

13. Patients who have received an investigational product within 12 weeks prior to Baseline 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 (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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Eisai Inc

Principal Investigators

Jonathan Webster

Role: STUDY_DIRECTOR

Eisai Limited

Locations

Clinic of Neurology, Faculty Hospital Olomouc

Olomouc, , Czechia

Private Neurology Practise

Ostrava, , Czechia

Department of Neurology, Regional Hospital Pardubice

Pardubice, , Czechia

First Faculty of Medicine Charles University

Prague, , Czechia

Dept. of Neurology - Second Faculty of Medicine Charles University

Prague, , Czechia

Centre D'Investigation Clinique Pavillon Riser - Hopital Purpan

Toulouse, , France

Parkinson's Competence Network Germany Dept. of Neurology - Philipps-University Marburg

Marburg, Hesse, Germany

Humboldt Universit?t Charite Neurologische Klinik

Berlin, , Germany

Klinikum der Friedrich-Wilhelms- Univerit?t Bonn

Bonn, , Germany

Zentralkrankenhaus Reinkenheide Neurologische Klinik

Bremerhaven, , Germany

Klinikum der Heinrich-Heine- Universit?t

D?sseldorf, , Germany

Praxis

Erbach im Odenwald, , Germany

Klinikum der Georg-August- Universit?t

G?ttingen, , Germany

Universit?tskrankenh aus Hamburg Eppendorf

Hamburg, , Germany

Krankenhaus Hanau

Hanau, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universit?tsklinikum Heidelberg

Heidelberg, , Germany

Universit?tsklinikum

Homburg/Saar, , Germany

Paracelsus-Elena-Kli nik

Kassel, , Germany

Hopital Roger Salengro

Lille, , Germany

Universit?tsklinikum Rostock Klinik f?r Neurologie

Rostock, , Germany

Reparto di Neurologia - Ospedale Misericordia

Grosseto, , Italy

Universit? di Napoli Federico II

Napoli, , Italy

Unit? Operativa Parkinson e Disordini del Movimento

Pavia, , Italy

Istituto Neuromed SRL Neurologia

Pozzilli, , Italy

III Clinica Neurologica

Roma, , Italy

Militzary Medical Academy

Belgrade, , Serbia

Clinic of Neurology

Belgrade, , Serbia

Institute of Neurology

Belrade, , Serbia

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Clinic I Provincial de Barcelona

Barcelona, , Spain

Hospital Mutua de Terrassa

Terrassa, , Spain

Countries

Czechia; France; Germany; Italy; Serbia; Spain

Other Identifiers

E2007-E044-204

Identifier Type: -

Identifier Source: org_study_id