A Study of E2007 as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations

This study has been terminated.
(Study stopped due to lack of efficacy.)
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00360412
First received: August 2, 2006
Last updated: June 26, 2014
Last verified: August 2013
  Purpose

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 Patients not tolerating 2 mg will be withdrawn from the study.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


Condition Intervention Phase
Parkinson's Disease
Drug: E2007
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 20, Week 32, Week 44, Week 56, Week 68 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 20, Week 32, Week 44, Week 56, Week 68 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study [ Time Frame: Baseline, Week 0, Week, 8, Week 20, Week 32, Week 44, Week 56, Week 68 ] [ Designated as safety issue: No ]
    Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. 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, for a range of total possible scores of 0-52. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.

  • Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open- Label Extension Study [ Time Frame: Baseline, Week 0, Week 8, Week 20, Week 32, Week 44, Week 56, Week 68 ] [ Designated as safety issue: No ]
    Unified Parkinson's Disease Rating Scale (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, for a range of total possible scores of 0-56. ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor.


Enrollment: 997
Study Start Date: October 2006
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E2007
During the first two weeks of the study, Patients received 1 x 2mg E2007 tablet. At the week 2 visit, patients who tolerated the 2 mg/day dose were up-titrated to receive 4mg/day (2 x 2 mg E2007 tablets). Patients not tolerating the 4 mg dose were allowed to down titrate to 2 mg. Patients who did not tolerate the 2 mg dose were withdrawn from the study. Patients returned at week 4, if their tolerance to the 4 mg/day dose was acceptable they remained on this dose for the maintenance phase of the study. If at any time their tolerance declined, they were to return for an unscheduled visit and the daily dose was reduced to 2 mg. If at any stage, 2 mg day wass not tolerated, the patient was withdrawn from the study.
Drug: E2007

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00360412

Locations
Germany
Philipps-University Marburg
Marburg, Germany, 35039
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: David Squillacote, M.D. Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00360412     History of Changes
Other Study ID Numbers: E2007-G000-303, 2006-002339-26
Study First Received: August 2, 2006
Results First Received: October 23, 2012
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014