Clinical trial NCT00360412: A Study of E2007 as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations
Official title: A Multi-centre, Open Label Extension Study to Evaluate the Long-term Safety, Tolerability and Efficacy of E2007 as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2006-08-04
Enrollment: 997
Sex: MALE
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 Patients not tolerating 2 mg will be withdrawn from the study.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.

Primary outcomes:
measure: Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 20, Week 32, Week 44, Week 56, Week 68
Secondary outcomes:
measure: Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 20, Week 32, Week 44, Week 56, Week 68
measure: Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study
timeFrame: Baseline, Week 0, Week, 8, Week 20, Week 32, Week 44, Week 56, Week 68
measure: Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study
timeFrame: Baseline, Week 0, Week 8, Week 20, Week 32, Week 44, Week 56, Week 68
Other outcomes:
Locations:
city: Marburg
country: Germany
facility: Philipps-University Marburg
Study officials:
affiliation: Eisai Inc.
name: David Squillacote, M.D.
role: STUDY_DIRECTOR
References: