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

• Register: EUCTR
• Last refreshed on: 7 April 2015
• Main ID: EUCTR2005-004314-33-CZ
• Date of registration: 11/01/2006
• Prospective Registration: Yes
• Primary sponsor: Eisai Limited
• Public 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
• Scientific 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
• Date of first enrolment: 01/02/2006
• Target sample size: 1260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004314-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Czech Republic, Estonia, Germany, Hungary, Italy, Lithuania, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion 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 as confirmed by diary data collected between screening and baseline visits
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 screening visit 1 there must be diary evidence of at least one transition of OFF to ON or from ON to OFF.
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 investigators 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 baseline 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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-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 Screening 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 Screening visit) with medication known to induce the enzyme cytochrome P450 3A4 (section 8.7.2 of the protocol).
10. Current or prior treatment (within 4 weeks prior to Screening 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 6months) deep brain stimulation.
13. Patients who have received an investigational medicinal 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Levodopa treated Parkinson's disease patients with motor fluctuations
MedDRA version: 8.1 Classification code 10061536

Intervention(s)

Product Name: MARS
Product Code: E2007
Pharmaceutical Form: Film-coated tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: MARS
Product Code: E2007
Pharmaceutical Form: Film-coated tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change from baseline to final efficacy visit in the mean total daily OFF time (hr) as measured by patient completed home diary cards.

A secondary analysis of the primary endpoint will be undertaken using a responder analysis: Percentage of patients with total mean daily OFF time reduction of = 1 hr.

Secondary Objective: To compare the efficacy of 2mg and 4mg of E2007 and placebo on levodopa-induced dyskinesias.
To compare the safety and tolerability of E2007 and placebo.

Main Objective: To compare the efficacy of 2mg and 4mg of E2007 and placebo on motor function in patients with Parkinson's disease who are on optimised and stabilised therapy and experience end-of-dose 'wearing off' motor fluctuations.

Secondary ID(s)

2005-004314-33-BE

E2007-E044-301