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

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00165789
• Other study ID #: E2007-A001-214
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: May 28, 2015
• Start date: September 2005
• Est. completion date: September 2006

Study information

• Verified date: April 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: September 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• E2007

Locations

Country	Name	City	State
United States	Inc.	Boca Raton	Florida
United States	Brain Matters Research	Delray Beach	Florida
United States	Clinical Trials Incorporated	Little Rock	Arkansas
United States	The Clinical Neuroscience Center	Lubbock	Texas
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	New Haven	Connecticut
United States	UMDNJ - Robert Wood Johnson Medical School	Oxnard	California
United States	Agape Medical Research Center	Piscataway	New Jersey
United States	Inc.	Raleigh	North Carolina
United States	Raleigh Neurology Associates	Southfield	Michigan
United States	Suncoast Neuroscience Associates	St. Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Any TEAE	Treatment-emergent Adverse Events (TEAEs) were defined as those adverse events (AEs) that started on or after the first dose of study medication until the end of the study. Information on any AEs were recorded throughout the study after informed consent had been signed and included abnormal clinical laboratory tests, vital sign measurements and physical examinations. Note: Safety/tolerability info captured in Adverse Event section.	Through end of study	No
Secondary	Change From Baseline to Day 70 in "on" State of UPDRS Scores	The Unified Parkinson's Disease Rating Scale (UPDRS) consisted of 4 subsections used to assess symptoms and signs of Parkinson's disease, with an overall scale range of 0-147. Individual subsections included: I. Mentation, behavior, and mood (0-16); II. Activities of daily living assessed in both the "on" and "off" state (0-52); III. Motor examination (0-56); and IV. Complications of therapy assessed in the "on" fluctuations and dyskinesias (0-23). Each subsection included subscales that ranged from 0 (best possible outcome) to 1 or 4 (worst possible outcome), with the total score of subsection equaling the sum of the scores of the subscales and the overall UPDRS score equaling the sum of the scores of the 4 subsections (higher score indicating more severe Parkinson's Disease).	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Absolute "Off" Time	Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Absolute "on" Time With Non-troublesome Dyskinesias	Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Absolute "on" Time With Troublesome Dyskinesias	Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Goetz/Rush Score	The Goetz/Rush scale was used to rate severity during performance of tasks intended to elicit dyskinesias, and provided an objective rating of dyskinesias during activities of daily living.The tasks included a sitting exercise, mental calculations, drinking, dressing, and walking. A 5-point scale was used: 0=absent; 1=minimal severity, no interference with voluntary motor acts; 2=dyskinesias, may impair voluntary movements but the subject was capable of efficiently completing the motor task; 3=intense dyskinesias, interference with movement control and completion of the motor task was greatly limited; 4= violent dyskinesias, incompatible with the completion of the motor task. A lower score indicated less difficulty performing the tasks.	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Percent "Off" Time	Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Percent "on" Time	Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.	Baseline and Day 70	No
Secondary	Change From Baseline to Day 70 in Percent "on" Time With Non-troublesome Dyskinesias	Subjects and/or caregiver completed a diary recording their motor state and dyskinesia symptoms over the course of the day before and at the end of study drug dosing on 3 consecutive days leading up to Baseline and Day 70. An entry was made every 30 minutes whether they were in the "on" state experiencing troubling dyskinesias or "off" state. The "on" state reflected recovery of control of a particular Parkinsonian feature that readily responded to each dose of levodopa, while the "off" state reflected the re-emergence of that feature. Troublesome dyskinesias were unintentional movements that occurred while in the "on" state and which interfered with activities or caused discomfort to any extent.	Baseline and Day 70	No
Secondary	Disability of Dyskinesia From UPDRS at Baseline and Day 70	The disability of dyskinesia was determined from question 33 (part 4) of the UPDRS assessment. It asks how disabling are the dyskinesias, and uses a 5-part scale: 0=Not disabling, 1=MIldly disabling, 2=Moderately disabling, 3=Severely disabling, 4=Completely disabling. Lower scores represented more normal functioning.	Baseline and Day 70	No
Secondary	Duration of Dyskinesia From UPDRS at Baseline and Day 70	The duration of dyskinesia was determined from question 32 (part 4) of the UPDRS assessment. It asks what proportion of the waking day are dyskinesias present, and uses a 5-part scale: 0 = None, 1 = 1-25% of day, 2 = 26-50% of day, 3 = 51-75% of day, 4 = 76-100% of day. Lower scores represented more normal functioning.	Baseline and Day 70	No