Patients with idiopathic Parkinson's disease who respond to levodopa treatment but who experience peak-effect levodopa-induced dyskinesia and end-of-dose 'wearing-off' motor fluctuations MedDRA version: 6.1 Level: HLT Classification code 10034005
Conditions
Interventions
Product Name: E2007
Product Code: E2007
Pharmaceutical Form: Tablet
INN or Proposed INN: OTHER NERVOUS SYSTEM DRUGS
Current Sponsor code: E2007
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
EISAI LTD UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women aged between 30 and 80 years, inclusive 2. A diagnosis of idiopathic Parkinson's disease. Patients should fulfill the UK Parkinson?s Disease Society Brain Bank clinical diagnostic criteria (Queen Square criteria) and have a rating of 2?4 on the Hoehn &Yahr scale9 when in an 'off' state. 3. Receiving a regimen of anti-Parkinsonian treatments that has been optimized (according to the Investigator's opinion) and has been stable for at least four weeks before baseline. The regimen is not considered to be stable if 'as required' or 'on demand' dosing is routinely used or there is regular use of apomorphine or liquid forms of levodopa. 4. Taking levodopa at least three times during the waking day (not including bedtime or nighttime doses) and with a demonstrable response to each levodopa dose. 5. Consistently experiencing clinically-relevant, peak-effect levodopa-induced dyskinesias during the 'on' period following the morning dose of levodopa. Patients should: a. score 2 on Questions 32 and 33 of the full UPDRS at screening. b. have at least 3 h of 'on' time with dyskinesias on average per day recorded in the patient diary at baseline, of which 1 h is within the 4 h following the first morning dose of levodopa. 6. Consistently experiencing end-of-dose motor fluctuations. Patients should: a. score 1 on Question 39 of the full UPDRS at screening. b. have at least 1.5 h of 'off' time on average per day recorded in the patient diary at baseline. 7. Capable of adhering to the protocol requirements and providing 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
Exclusion criteria: 1. A history of drug or alcohol abuse. 2. A history of suicide attempt or suicidal ideation within the past year. 3. Receiving antipsychotic treatment or a history of psychotic symptoms requiring antipsychotic treatment within the past year. Patients taking anti-depressant medications can enter the study providing the regimen is stable. 4. Receiving treatment with monoamine oxidase (MAO)-B inhibitors (eg, selegiline, rasagiline). 5. Receiving treatment with medication known to induce CYP3A4 activity. 6. Receiving treatment with medications believed to have an effect on levodopa-induced dyskinesias (eg, amantadine, dextromethorphan, clozapine, olanzapine, quetiapine). 7. Receiving treatment with medications known to exacerbate dyskinesias (eg, sodium valproate, CNS stimulants). 8. Failing to respond to the specified levodopa challenge, or where the levodopa challenge is not medically appropriate. 9. Experiencing dyskinesias unrelated to peak levodopa effect (eg, ''D-I-D'' pattern). 10. Previous stereotactic surgery (eg, pallidotomy, subthalamic nucleus deep brain stimulation) for Parkinson's disease. 11. Having received an investigational product within the four weeks leading up to Screening or having participated in a previous study with E2007. 12. Clinically significant cognitive impairment (mini-mental state examination [MMSE] <26 or fulfilling DSM IV criteria for dementia due to Parkinson's disease). 13. Active hepatic disease, significantly reduced hepatic function or significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper limit of the normal range). 14. Clinically significant ECG abnormalities, including prolonged QT interval (defined as QTc 450 msec). 15. Narrow-angle glaucoma 16. Conditions affecting the peripheral or central sensory system that could interfere with pharmacodynamic evaluations of the effects of levodopa. 17. Women who are pregnant or lactating, or who are intending to become pregnant within two months of completion of the study. 18. Women of child-bearing potential who do not agree to use adequate non-hormonal contraception (eg, intrauterine device, condoms with spermicide) throughout the study. 19. A history of drug hypersensitivity, especially hypersensitivity to any component of the investigational products or medication used for levodopa challenges. 20. A history of melanoma or suspicious, undiagnosed skin lesions. 21. Any condition that could, in the opinion of the Investigator, place the patient at increased risk or is likely to prevent completion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To quantify the effect of E2007 on levodopa-induced dyskinesia among patients with Parkinson's disease who respond to levodopa treatment but who experience peak-effect levodopa-induced dyskinesia and end-of-dose 'wearing-off' motor fluctuations.;Secondary Objective: To quantify the effect of E2007 on motor responses to levodopa. To assess the effect of E2007 treatment on the relationships between levodopa concentration and pharmacodynamic measures of dyskinesia and motor response. To explore the relationship between E2007 concentrations and changes in levodopa-induced dyskinesia and motor responses to levodopa. To investigate the effect of E2007 on the pharmacokinetics of levodopa in combination with a peripheral decarboxylase inhibitor. To further explore the safety and tolerability of E2007;Primary end point(s): Pharmacodynamic assessments of dyskinesias and motor function will be made after each levodopa challenge. Goetz/Rush dyskinesia rating scale, modified abnormal involuntary movement scale (modified AIMS), and Unified Parkinson's disease rating scale motor examination sub-scale (UPDRS Part 3) scores will be recorded before (-0.5 h) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4 and 5 h after levodopa dosing (or until a full off-state is reached if earlier than 5 h) on Days -1, 21 and 42. Goetz/Rush, modified AIMS and UPDRS assessments will be made by three blinded raters from videotaped recordings of patients engaged in a specified series of simple tasks known to elicit dyskinesias | — |
Countries
Italy
Outcome results
None listed