Clinical trial NCT01172379: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-29
Enrollment: 2
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Efficacy assessments: Parkinsonian symptomology will be recorded on an out-patient basis using patient diary cards (indicating "on" and "off" periods, sleep and dyskinesias).
timeFrame: 12 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Olomouc
country: Czech Republic
facility: Clinic of Neurology, Faculty Hospital Olomouc
city: Ostrava
country: Czech Republic
facility: Private Neurology Practise
city: Pardubice
country: Czech Republic
facility: Department of Neurology, Regional Hospital Pardubice
city: Prague
country: Czech Republic
facility: First Faculty of Medicine Charles University
city: Prague
country: Czech Republic
facility: Dept. of Neurology - Second Faculty of Medicine Charles University
city: Toulouse
country: France
facility: Centre D'Investigation Clinique Pavillon Riser - Hopital Purpan
city: Marburg
country: Germany
facility: Parkinson's Competence Network Germany Dept. of Neurology - Philipps-University Marburg
state: Hesse
city: Berlin
country: Germany
facility: Humboldt Universit?t Charite Neurologische Klinik
city: Bonn
country: Germany
facility: Klinikum der Friedrich-Wilhelms- Univerit?t Bonn
city: Bremerhaven
country: Germany
facility: Zentralkrankenhaus Reinkenheide Neurologische Klinik
city: D?sseldorf
country: Germany
facility: Klinikum der Heinrich-Heine- Universit?t
city: Erbach
country: Germany
facility: Praxis
city: G?ttingen
country: Germany
facility: Klinikum der Georg-August- Universit?t
city: Hamburg
country: Germany
facility: Universit?tskrankenh aus Hamburg Eppendorf
city: Hanau
country: Germany
facility: Krankenhaus Hanau
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universit?tsklinikum Heidelberg
city: Homburg/Saar
country: Germany
facility: Universit?tsklinikum
city: Kassel
country: Germany
facility: Paracelsus-Elena-Kli nik
city: Lille
country: Germany
facility: Hopital Roger Salengro
city: Rostock
country: Germany
facility: Universit?tsklinikum Rostock Klinik f?r Neurologie
city: Grosseto
country: Italy
facility: Reparto di Neurologia - Ospedale Misericordia
city: Napoli
country: Italy
facility: Universit? di Napoli Federico II
city: Pavia
country: Italy
facility: Unit? Operativa Parkinson e Disordini del Movimento
city: Pozzilli
country: Italy
facility: Istituto Neuromed SRL Neurologia
city: Roma
country: Italy
facility: III Clinica Neurologica
city: Belgrade
country: Serbia
facility: Militzary Medical Academy
city: Belgrade
country: Serbia
facility: Clinic of Neurology
city: Belrade
country: Serbia
facility: Institute of Neurology
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
Study officials:
affiliation: Eisai Limited
name: Jonathan Webster
role: STUDY_DIRECTOR
References: