The Effect Of E2007 On Pharmacodynamic Responses To Levodopa Among Patients With Parkinson's Disease Who Experience Dyskinesia And Motor Fluctuations

This study has been withdrawn prior to enrollment.
(The study group changed from patients to a healthy volunteers. A healthy-volunteer study is being planned to replace 213.)
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00451633
First received: March 21, 2007
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

A randomized, double blind, placebo-controlled study employing a mixed parallel group and fixed sequence cross-over design.

Patients will be randomized to one of two treatment groups ('E2007' or 'Placebo') in a 1:1 ratio and receive investigational drug treatment concomitant with their standard individualized anti-Parkinsonian therapy for a total of six weeks. Investigational drug treatment for patients in the E2007 treatment group will be started 2 mg E2007 o.d. but will be escalated to 4 mg E2007 o.d. after three weeks.


Condition Intervention Phase
Parkinson's Disease
Drug: E2007
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-Controlled Study To Investigate The Effect Of E2007 On Pharmacodynamic Responses To Levodopa Among Patients With Parkinson's Disease Who Experience Dyskinesia And Motor Fluctuations

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Levodopa pharmacokinetics will be assessed after each levodopa challenge. Blood samples for measurement of levodopa plasma
  • concentrations will be taken before and after levodopa dosing or until a full 'off' state is reached if earlier than 5 h.

Secondary Outcome Measures:
  • Pharmacodynamic assessments of dyskinesias and motor function; Goetz/Rush dyskinesia rating scale; modified abnormal involuntary movement scale (AIMS), and Unified Parkinson's disease rating scale motor examination sub-scale (UPDRS Part 3) scores.

Enrollment: 0
Study Start Date: March 2007
  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Patients will be eligible for the study if they meet all of the following inclusion criteria. Eligibility will be checked at screening and re-confirmed before the start of investigational drug dosing on Day -1 (ie, after completion and review of pre-dosing patient diaries and baseline assessments).

  1. Men or women aged between 30 and 80 years, inclusive.
  2. A diagnosis of idiopathic Parkinson's disease. Patients should fulfill the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (Queen Square criteria) and have a rating of 2.4 on the Hoehn &Yahr scale when in an "off" state.
  3. Receiving a regimen of anti-Parkinsonian treatments that has been optimized (according to the Investigator's opinion) and has been stable for at least four weeks before baseline. The regimen is not considered to be stable if 'as required' or 'on demand' dosing is routinely used or there is regular use of apomorphine or liquid forms of levodopa.
  4. Taking levodopa at least three times during the waking day (not including bedtime or nighttime doses) and with a demonstrable response to each levodopa dose.
  5. Consistently experiencing clinically-relevant, peak-effect levodopa-induced dyskinesias during the 'on' period following the morning dose of levodopa. Patients should:

    1. score .2 on Questions 32 and 33 of the full UPDRS at screening.
    2. have at least 3 h of 'on' time with dyskinesias on average per day recorded in the patient diary at baseline, of which 1 h is within the 4 h following the first morning dose of levodopa.
  6. Consistently experiencing end-of-dose motor fluctuations. Patients should:

    1. score .1 on Question 39 of the full UPDRS at screening.
    2. have at least 1.5 h of 'off' time on average per day recorded in the patient diary at baseline.
  7. Capable of adhering to the protocol requirements and providing written informed consent.

EXCLUSION CRITERIA:

Patients who meet any of the following exclusion criteria will not eligible for the study.

Eligibility will be checked at the Screening visit and re-confirmed before the start of investigational drug dosing on Day -1 (i.e., after completion and review of pre-dosing patient diaries and baseline assessments). All exclusion criteria must be observed.

  1. A history of drug or alcohol abuse.
  2. A history of suicide attempt or suicidal ideation within the past year.
  3. Receiving antipsychotic treatment or a history of psychotic symptoms requiring antipsychotic treatment within the past year. Patients taking anti-depressant medications can enter the study providing the regimen is stable.
  4. Receiving treatment with monoamine oxidase (MAO)-B inhibitors (e.g., selegiline, rasagiline).
  5. Receiving treatment with medication known to induce CYP3A4 activity.
  6. Receiving treatment with medications believed to have an effect on levodopa-induced dyskinesias (e.g., amantadine, dextromethorphan, clozapine, olanzapine, quetiapine).
  7. Receiving treatment with medications known to exacerbate dyskinesias (eg, sodium valproate, CNS stimulants).
  8. Failing to respond to the specified levodopa challenge, or where the levodopa challenge is not medically appropriate.
  9. Experiencing dyskinesias unrelated to peak levodopa effect (e.g., "D-I-D" pattern).
  10. Previous stereotactic surgery (e.g., pallidotomy, subthalamic nucleus deep brain stimulation) for Parkinson's disease.
  11. Having received an investigational product within the four weeks leading up to Screening or having participated in a previous study with E2007.
  12. Clinically significant cognitive impairment (mini-mental state examination [MMSE] <26 or fulfilling DSM IV criteria for dementia due to Parkinson's disease).
  13. 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).
  14. Clinically significant ECG abnormalities, including prolonged QT interval (defined as QTc .450 msec).
  15. Narrow-angle glaucoma.
  16. Conditions affecting the peripheral or central sensory system that could interfere with pharmacodynamic evaluations of the effects of levodopa.
  17. Women who are pregnant or lactating, or who are intending to become pregnant within two months of completion of the study.
  18. Women of child-bearing potential who do not agree to use adequate non-hormonal contraception (e.g., intrauterine device, condoms with spermicide) throughout the study.
  19. A history of drug hypersensitivity, especially hypersensitivity to any component of the investigational products or medication used for levodopa challenges.
  20. A history of melanoma or suspicious, undiagnosed skin lesions.
  21. 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.
  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: NCT00451633

Locations
Germany
St. Josef Hospital
Bochum, Germany, 44791
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Neurologische Universitatsklinik Marburg
Marburg, Germany, D-35039
Italy
CESI - Centro Ricerche Cliniche - Fondazione Universita degli Studi
Chieti, Italy, 66013
U.O. Riabilitazione Neuromotoria, IRCCS San Raffaele Pisana
Roma, Italy, 00163
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Alessia Nicotra, M.D., Ph.D. Eisai Limited
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00451633     History of Changes
Other Study ID Numbers: E2007-E044-213
Study First Received: March 21, 2007
Last Updated: October 30, 2013
Health Authority: European Union: European Medicines Agency

Additional relevant MeSH terms:
Dyskinesias
Parkinson Disease
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
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 July 22, 2014