A Study of E2007 In Patients With Parkinson's Disease

A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of E2007 In Patients With Parkinson's Disease Who Experience End-of-Dose "Wearing-Off" Motor Fluctuations

Phase IIb open-label extension study for patients with Parkinson's Disease. All patients will receive active study drug. The study will involve outpatient visits only. Patients who completed Study E2007-A001-214 (Cohorts I and II) and who meet inclusion/exclusion criteria will be enrolled and enter the 12-week Titration Phase (from "Dispense Study Drug" at Week 0 [Visit 2] through Week 12 [Visit 7]) followed by the Maintenance Phase (from Week 12 [Visit 7] to end of study).

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: E2007

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Pivotal Research Centers
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials Incorporated
  • California
    • Oxnard, California, United States, 93030
      • Pacific Neuroscience Medical Group
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Port Charlotte, Florida, United States, 33952
      • Charlotte Neurological Services
    • St. Petersburg, Florida, United States, 33701
      • Suncoast Neuroscience Associates, Inc.
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Texas
    • Lubbock, Texas, United States, 79410
      • Agape Medical Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

1. Male or female patients with idiopathic Parkinson's disease who have fulfilled the entry criteria for E2007-A001-214 and have completed that study up to and including the end of treatment (Day 70) visit and the Follow-up Visit at Day 91.

EXCLUSION CRITERIA

1. Pregnant or lactating women.
2. Women of child bearing potential unless infertile (including surgically sterile) or practicing effective contraception (e.g., intrauterine device or barrier method plus hormonal method). These patients must have a negative serum beta human chorionic gonadotropin (B-HCG) test at the initial visit (Visit 1) and urine pregnancy tests throughout the study. 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 nonchildbearing potential as determined by the investigator.
3. Patients who withdrew from Study 214 prior to the final efficacy visit for any reason, including lack of efficacy.
4. Patients with serious adverse events in Study 214 that are either ongoing or that are possibly or probably related to the study drug.
5. Patients with ongoing adverse events from Study 214 thought to be related to E2007.
6. Patients with a past (within the past 5 years) or present history of drug or alcohol abuse as per the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV).
7. Patients with a past (within 1 year) or present history of psychotic symptoms requiring antipsychotic treatment.
8. Patients with a past (within 1 year) or present history of suicidal ideation or suicide attempts.
9. Patients with 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).
10. Patients with clinically significant ECG abnormality, including prolonged QTc (defined as QTc >= 450 msec using Fridericia's correction).
11. Patients with clinically significant cardiovascular, metabolic, respiratory, renal, endocrinological, gastrointestinal diseases, psychiatric disorders, and bacterial or viral infections within the previous 30 days.
12. Patients who are currently taking medications known to induce the enzyme cytochrome P450 3A4.
13. Patients with current or prior treatment (within 4 weeks before entry visit) with tolcapone, methyldopa, budipine, reserpine, seroquel, or intermittent use of either liquid forms of levodopa or subcutaneous apomorphine.
14. Patients with previous stereotactic surgery (e.g., pallidotomy) for Parkinson's disease or with planned stereotactic surgery during the study period.
15. Patients receiving or with planned (next 6 months) deep brain stimulation.
16. 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.
17. Patients with any condition that would make the patient, in the opinion of the investigator, unsuitable for the study.
18. Patients who have received an investigational product (other than E2007) within 4 weeks before screening.
19. Patients with clinically significant cognitive impairment (mini-mental state examination [MMSE] <24 or fulfilling DSM IV criteria for dementia due to Parkinson's disease).
20. Patients with 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: E2007; E2007 2mg tablets. Dose (2mg, 4mg, 6mg or 8mg), is taken orally at nighttime.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline by Visit in Absolute OFF Time (Hours) During Open-label Extension Study	OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. This outcome measure was based on data collected through use of a patient diary.	Baseline, Week 12, Week 20, Week 32, Week 44, Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline by Visit in Absolute ON Time (Without Dyskinesias or With Nontroublesome Dyskinesias) (Hours) During Open-label Extension Study	ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. This outcome measure was based on data collected through use of a patient diary.	Baseline, Week 12, Week 20, Week 32, Week 44, Week 56
Mean Change From Baseline by Visit in UPDRS Part II (ADL) in OFF State (Hours) During Open-label Extension Study	Unified Parkinson's Disease (PD) Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of PD. Part II assesses Activities of Daily Living (ADL) based on 13 items, such as speech, hygiene, and falling. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. Range of possible total scores, 0 to 52. ON state is when medication is providing benefits to mobility, slowness, and stiffness. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.	Baseline, Week 12, Week 20, Week 32, Week 44, Week 56
Mean Change From Baseline by Visit in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study	The UPDRS is a standardized assessment of the symptoms and signs of Parkinson's Disease. Part III assesses motor activity, based on 14 items, such as gait, facial expression, and rigidity. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. Range of possible total scores, 0 to 56. ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor.	Baseline, Week 12, Week 20, Week 32, Week 44, Week 56

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: David Squillacote, MD, Eisai Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: January 24, 2007
• First Submitted That Met QC Criteria: January 25, 2007
• First Posted (Estimate): January 26, 2007

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: February 5, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: E2007-A001-220