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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172379
• Other study ID #: E2007-E044-204
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2010
• Last updated: August 21, 2014
• Start date: May 2004

Study information

• Verified date: August 2014
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Europe: European Agency for the Evaluation of Medicinal Products
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyskinesias
• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• E2007
Experimental 1 Drug: E2007 0.5 mg 1 tablet per day
• E2007
Experimental 2 Drug: E2007 1.0 mg 1 tablet per day
• E2007
Drug: E2007 2.0 mg 1 tablet per day

Other:
• Placebo Comparator
Placebo 1 tablet per day

Locations

Country	Name	City	State
Czech Republic	Clinic of Neurology, Faculty Hospital Olomouc	Olomouc
Czech Republic	Private Neurology Practise	Ostrava
Czech Republic	Department of Neurology, Regional Hospital Pardubice	Pardubice
Czech Republic	Dept. of Neurology - Second Faculty of Medicine Charles University	Prague
Czech Republic	First Faculty of Medicine Charles University	Prague
France	Centre D'Investigation Clinique Pavillon Riser - Hopital Purpan	Toulouse
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
Germany	Klinikum der Georg-August- Universit?t	G?ttingen
Germany	Universit?tskrankenh aus Hamburg Eppendorf	Hamburg
Germany	Krankenhaus Hanau	Hanau
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universit?tsklinikum Heidelberg	Heidelberg
Germany	Universit?tsklinikum	Homburg/Saar
Germany	Paracelsus-Elena-Kli nik	Kassel
Germany	Hopital Roger Salengro	Lille
Germany	Parkinson's Competence Network Germany Dept. of Neurology - Philipps-University Marburg	Marburg	Hesse
Germany	Universit?tsklinikum Rostock Klinik f?r Neurologie	Rostock
Italy	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
Serbia	Clinic of Neurology	Belgrade
Serbia	Militzary Medical Academy	Belgrade
Serbia	Institute of Neurology	Belrade
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Mutua de Terrassa	Terrassa

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Limited

Countries where clinical trial is conducted

Czech Republic,  France,  Germany,  Italy,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy assessments: Parkinsonian symptomology will be recorded on an out-patient basis using patient diary cards (indicating "on" and "off" periods, sleep and dyskinesias).		12 Weeks	No