Clinical trial NCT00165789: A Study to Explore the Safety And Tolerability of Doses of E2007 Up to a Maximum of 8 mg In Patients With Parkinson's Disease Who Experience End-of-Dose Wearing Off Motor Fluctuations
Official title: A Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Explore the Safety And Tolerability of Doses of E2007 Up to a Maximum of 8 mg In Patients With Parkinson's Disease Who Experience End-of-Dose Wearing Off Motor Fluctuations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2005-09-14
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: This is a randomized, double-blind, two treatment, two group, parallel group study. Subjects will be randomized to one of two treatment groups (E2007 or Placebo) in a 3 to 1 ratio and receive treatment for a total of ten weeks (Days 1 to 70).


Eligibility criteria: Inclusion Criteria:

* Subjects of any race greater than or equal to 30 years of age
* Have a diagnosis of idiopathic Parkinson's disease. Subjects 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 and Yahr scale when in an 'off' state.
* Receiving an optimized regimen of anti-Parkinsonian treatments that 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.
* Taking levodopa or levodopa-containing medications (e.g. co-beneldopa, cocareldopa) at least three times daily with a good response to each levodopa dose as evidenced from patient diaries or medical notes.
* Consistently experience end-of-dose "wearing-off" motor fluctuations. Subjects should:
* score greater than or equal to 1 on Question 39 (What proportion of the waking day is the patient "off" on average?) of the full UPDRS at screening.
* have at least 2.5 hours of "off" time on average per day recorded in the patient diary at baseline.
* Willing and able to provide written informed consent and adhere to the protocol requirements, including completion of a patient diary.

Exclusion Criteria:

* Receiving treatment with medication known to induce CYP3A4 activity
* Previous stereotactic surgery (e.g. pallidotomy, subthalamic nucleus deep brain stimulation) for Parkinson's disease
* Received an investigational product within four weeks prior to screening or having participated in a previous study with E2007.
* Clinically significant cognitive impairment \[mini-mental state examination (MMSE) less than 24 or fulfilling DSM IV criteria for dementia due to Parkinson's disease\].
* 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).
* Clinically significant ECG abnormality, including prolonged QTc (defined as QTc greater than or equal to 450 msec for males and greater than or equal to 470 msec for females using Fridericia's correction).
* Clinically significant, cardiovascular, metabolic, respiratory, renal, endocrinological, gastrointestinal diseases, psychiatric disorders, and bacterial or viral infections within the previous 30 days.
* History of drug or alcohol abuse.
* Women who are pregnant or lactating.
* Any condition that could, in the opinion of the investigator, place the subject at increased risk or is likely to prevent completion of the study

Primary outcomes:
measure: Number of Participants With Any TEAE
timeFrame: Through end of study
Secondary outcomes:
measure: Change From Baseline to Day 70 in "on" State of UPDRS Scores
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Absolute "Off" Time
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Absolute "on" Time With Non-troublesome Dyskinesias
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Absolute "on" Time With Troublesome Dyskinesias
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Goetz/Rush Score
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Percent "Off" Time
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Percent "on" Time
timeFrame: Baseline and Day 70
measure: Change From Baseline to Day 70 in Percent "on" Time With Non-troublesome Dyskinesias
timeFrame: Baseline and Day 70
measure: Disability of Dyskinesia From UPDRS at Baseline and Day 70
timeFrame: Baseline and Day 70
measure: Duration of Dyskinesia From UPDRS at Baseline and Day 70
timeFrame: Baseline and Day 70
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Trials Incorporated
state: Arkansas
city: Oxnard
country: United States
facility: UMDNJ - Robert Wood Johnson Medical School
state: California
city: New Haven
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Connecticut
city: Boca Raton
country: United States
facility: Inc.
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: St. Petersburg
country: United States
facility: Suncoast Neuroscience Associates
state: Florida
city: Southfield
country: United States
facility: Raleigh Neurology Associates
state: Michigan
city: Piscataway
country: United States
facility: Agape Medical Research Center
state: New Jersey
city: Raleigh
country: United States
facility: Inc.
state: North Carolina
city: Lubbock
country: United States
facility: The Clinical Neuroscience Center
state: Texas
Study officials:
affiliation: Eisai Inc.
name: Santiago Arroyo, M.D., Ph.D
role: STUDY_DIRECTOR
References: