The Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations

• Register: ClinicalTrials.gov
• Last refreshed on: 17 November 2015
• Main ID: NCT00286897
• Date of registration: 03/02/2006
• Prospective Registration: No
• Primary sponsor: Eisai Limited
• Public title: 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: February 2006
• Target sample size: 702
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00286897
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Czech Republic, Estonia, Former Serbia and Montenegro, France, Germany, Hungary, Israel, Italy, Lithuania, Poland, Portugal, Serbia, South Africa, Spain, Sweden, United Kingdom

Contacts

• Name: Alessia Nicotra, MD, PhD, DIC
• Affiliation: Eisai Limited

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 collected at the baseline visit.

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 the initial
screening visit there must be diary evidence of at least one transition of OFF to ON
or from ON to OFF and patients must show 75% concordance with Investigator's
completion of the diary card.

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 investigator's
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 screening 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.

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 (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 baseline 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 baseline visit)
with medication known to induce the enzyme cytochrome P450 3A4.

10. Current or prior treatment (within 4 weeks prior to the baseline 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 6 months) deep brain stimulation.

13. Patients who have received an investigational 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: 30 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Drug: E2007

Primary Outcome(s)

Patient diaries: Change from baseline to final efficacy visit in the mean total daily OFF time (hr).

Secondary Outcome(s)

Change from baseline on average OFF time over total treatment period; UPDRS Part II: OFF state; UPDRS Part III: ON state; change from baseline to final efficacy visit in mean total daily ON time w/o dyskinesias or with no troublesome dyskinesias.

Secondary ID(s)

2005-004314-33

E2007-E044-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors