A Study of E2007 as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: E2007
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 997.0
Sex: Male
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      Patients who have completed one of the core trials (E2007-E044-301 or E2007-A001-302) and who
      meet inclusion/exclusion criteria will be enrolled and will enter the Titration Phase,
      lasting 4 weeks (weeks 0-3) followed by the Maintenance Phase, lasting 52 weeks (weeks 4-56).
      All patients will receive active study drug. During the Titration Phase, patients will
      receive E2007 2 mg once daily (o.d.) for 2 weeks followed by 4 mg o.d. for 2 weeks. During
      the Maintenance Phase, patients will receive 4 mg o.d. Patients not tolerating the study drug
      at 4 mg, will be allowed to down titrate to 2 mg. Patients not tolerating 2 mg will be
      withdrawn from the study.

      Patients will have visits at 2, 4, 8, 20, 32, 44, and 56 weeks after study entry. In
      addition, a follow-up visit will occur 4 weeks after study treatment has ended (week 60).

      A home diary will be completed in which patients rate themselves as either:

        1. OFF

        2. ON without dyskinesia

        3. ON with non-troublesome dyskinesias

        4. ON with troublesome dyskinesias

        5. Asleep

      These entries will be completed every half hour during the waking day and will be completed
      for 3 consecutive days following the visits at weeks 4, 8, 20, 32 and 44, and three days
      prior to the visits at weeks 56 and 60. At entry into the study (week 0) and at weeks 8, 20,
      32, 44 and 56, the Unified Parkinson's Disease Rating Scale (UPDRS), Clinician's Global
      Impression of Change (CGIC) and Clinical Global Impression of Tolerance (CGIT) will be
      performed.
    

Eligibility criteria:

        Inclusion Criteria:

        Male or female patients with idiopathic PD who have fulfilled the entry criteria to either
        E2007-E044-301 or E2007-A001-302 and have completed that study up to and including the
        final efficacy visit. Patients will not be eligible if they withdrew from the core study
        prior to the final efficacy visit for any reason including lack of efficacy. Patients with
        SAEs which are ongoing or possibly or probably related to the study drug, will not be
        eligible for this study. Patients with ongoing adverse events categorized as severe and
        thought to be related to E2007 should not be entered. Patients with mild or moderate
        adverse events thought to be related to E2007 can be entered to the study if the
        investigator considers it safe.

        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 or urine B-HCG test at
             their first study 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 as determined by the investigator.

          3. Patients with a past (within the past 5 years) or present history of drug or alcohol
             abuse as per DSM IV criteria.

          4. Patients with a past (within one year) or present history of suicidal ideation or
             suicide attempts.

          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 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.

          7. Patients with significantly elevated liver enzymes (abnormal bilirubin or serum
             transaminase levels of more than 1.5 times the upper normal limit).

          8. Medication known to induce the enzyme cytochrome P450 3A4 is prohibited throughout the
             study.

          9. Current or prior treatment (within 4 weeks prior to entry visit) with tolcapone,
             methyldopa, budipine, reserpine, seroquel.

         10. 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.

         11. Patients receiving or with planned (next 12 months) deep brain stimulation.

         12. Patients with any condition that would make the patient, in the opinion of the
             Investigator, unsuitable for the study.

         13. Patients with clinically significant ECG abnormalities, including prolonged QTc
             (defined as QTc ≥ 450 msec).

         14. Patients with previous stereotactic surgery (e.g., pallidotomy) for Parkinson's
             disease or with planned stereotactic surgery during the study period.

         15. Patients on pergolide as of April 5, 2007.