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Efficacy, Safety, and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00368108
First Posted: August 24, 2006
Last Update Posted: May 20, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Eisai Inc.
Results First Submitted: October 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Parkinson's Disease
Interventions: Drug: 2 mg perampanel
Drug: 4 mg perampanel
Drug: placebo comparator

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.

Participant Flow:   Overall Study
    Placebo   Perampanel 2mg   Perampanel 4mg
STARTED   251 [1]   251   250 
COMPLETED   187   198   182 
NOT COMPLETED   64   53   68 
Adverse Event                38                26                44 
Abnormal Laboratory Value                0                0                3 
Protocol Violation                5                9                9 
Withdrawal by Subject                9                3                5 
Lack of Efficacy                7                8                5 
Physician Decision                2                0                1 
Not Specified                3                7                1 
[1] One subject had stopped medication prior to notifying staff. Remaining results will have 250.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.
Total Total of all reporting groups

Baseline Measures
   Placebo   Perampanel 2mg   Perampanel 4mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 250   251   250   751 
Age, Customized 
[Units: Participants]
       
<65 years   149   144   147   440 
≥ 65 years   101   107   103   311 
Gender 
[Units: Participants]
       
Female   86   87   86   259 
Male   164   164   164   492 
Race/Ethnicity, Customized 
[Units: Participants]
       
White   233   239   240   712 
Black   4   2   1   7 
Asian   5   4   1   10 
Other   8   6   8   22 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data)   [ Time Frame: Baseline and Week 20 ]

Measure Type Primary
Measure Title Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data)
Measure Description Patients described themselves in home diaries as "OFF", "ON" without dyskinesias, "ON" with non troublesome dyskinesias, "ON" with troublesome dyskinesias, or Asleep, every 30 minutes during waking hours for 3 consecutive days prior to Baseline, Weeks 8, 10, 18, and 20. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Time Frame Baseline and Week 20  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-to-treat (ITT) Population for diary data consisted of all subjects who were randomized to either perampanel or placebo, had taken at least 1 dose, had a valid, nonmissing Baseline diary measurement and at least 1 valid, non-missing, postbaseline diary measurement at Last Observation Carried Forward (LOCF).

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.

Measured Values
   Placebo   Perampanel 2mg   Perampanel 4mg 
Participants Analyzed 
[Units: Participants]
 208   213   201 
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data) 
[Units: Hours]
Least Squares Mean (95% Confidence Interval)
 -0.96 
 (-1.42 to -0.51) 
 -0.93 
 (-1.38 to -0.49) 
 -0.76 
 (-1.20 to -0.31) 

No statistical analysis provided for Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data)



2.  Secondary:   Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data)   [ Time Frame: Baseline and Week 20 ]

Measure Type Secondary
Measure Title Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data)
Measure Description Patients described themselves in home diaries every 30 minutes during waking hours for 3 consecutive days prior to Baseline, Weeks 8, 12, 16, and 20. 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.
Time Frame Baseline and Week 20  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.

Measured Values
   Placebo   Perampanel 2mg   Perampanel 4mg 
Participants Analyzed 
[Units: Participants]
 213   216   211 
Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data) 
[Units: Scores on a scale]
Least Squares Mean (95% Confidence Interval)
 -0.85 
 (-1.70 to -0.00) 
 -0.81 
 (-1.66 to 0.04) 
 -1.40 
 (-2.23 to -0.56) 

No statistical analysis provided for Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data)



3.  Secondary:   Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data)   [ Time Frame: Baseline and Week 20 ]

Measure Type Secondary
Measure Title Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data)
Measure Description Patients described themselves in home diaries every 30 minutes during waking hours for 3 days prior to Baseline, Weeks 8, 12, 16, and 20. UPDRS is a standardized assessment of the symptoms and signs of PD. 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. ON state is when medication is providing benefits to stiffness, slowness, and tremor.
Time Frame Baseline and Week 20  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.

Measured Values
   Placebo   Perampanel 2mg   Perampanel 4mg 
Participants Analyzed 
[Units: Participants]
 213   215   210 
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data) 
[Units: Scores on a Scale]
Least Squares Mean (95% Confidence Interval)
 -2.15 
 (-3.59 to -0.71) 
 -1.69 
 (-3.13 to -0.25) 
 -3.29 
 (-4.71 to -1.87) 

No statistical analysis provided for Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data)



4.  Secondary:   Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data)   [ Time Frame: Baseline and Week 20 ]

Measure Type Secondary
Measure Title Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data)
Measure Description Patients described themselves in home diaries every 30 minutes during waking hours for 3 days prior to Baseline, Weeks 8, 12, 16, and 20. ON state is when medication is providing benefits to stiffness, slowness, and tremor.
Time Frame Baseline and Week 20  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.

Measured Values
   Placebo   Perampanel 2mg   Perampanel 4mg 
Participants Analyzed 
[Units: Participants]
 208   213   201 
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data) 
[Units: Hours]
Least Squares Mean (95% Confidence Interval)
 0.73 
 (0.29 to 1.18) 
 0.78 
 (0.33 to 1.22) 
 0.28 
 (-0.15 to 0.72) 

No statistical analysis provided for Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data)




  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame From the time the subject signed the informed consent form to 30 days after the last dose of the study drug.
Additional Description Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Placebo The placebo dosage was a fixed dosage for the entire double-blind study. Subjects receiving the placebo were to take one dose orally once every day in the evening.
Perampanel 2mg The Perampanel 2mg dosage was fixed for the entire double-blind study. Subjects taking perampanel 2mg were to take the dose orally once every day in the evening.
Perampanel 4mg The Perampanel 4mg group first were subjected to a 4 week titration period, followed by a maintenance period for the remaining weeks. Subjects taking perampanel 4mg had a titration period of 4 weeks, starting at 2mg per day adding 1mg of perampanel every two weeks up to 4mg. The dosages were to be taken orally once every day in the evening.

Other Adverse Events
    Placebo   Perampanel 2mg   Perampanel 4mg
Total, Other (not including serious) Adverse Events       
# participants affected / at risk   111/250 (44.40%)   110/251 (43.82%)   144/250 (57.60%) 
Gastrointestinal disorders       
Nausea † 1       
# participants affected / at risk   16/250 (6.40%)   11/251 (4.38%)   12/250 (4.80%) 
Infections and infestations       
Urinary Tract Infection † 1       
# participants affected / at risk   10/250 (4.00%)   11/251 (4.38%)   13/250 (5.20%) 
Injury, poisoning and procedural complications       
Fall † 1       
# participants affected / at risk   23/250 (9.20%)   23/251 (9.16%)   19/250 (7.60%) 
Musculoskeletal and connective tissue disorders       
Back Pain † 1       
# participants affected / at risk   7/250 (2.80%)   16/251 (6.37%)   12/250 (4.80%) 
Nervous system disorders       
Balance Disorder † 1       
# participants affected / at risk   3/250 (1.20%)   6/251 (2.39%)   17/250 (6.80%) 
Dizziness † 1       
# participants affected / at risk   14/250 (5.60%)   15/251 (5.98%)   29/250 (11.60%) 
Dyskinesia † 1       
# participants affected / at risk   39/250 (15.60%)   21/251 (8.37%)   43/250 (17.20%) 
Headache † 1       
# participants affected / at risk   18/250 (7.20%)   10/251 (3.98%)   12/250 (4.80%) 
ON and OFF phenomenon † 1       
# participants affected / at risk   24/250 (9.60%)   18/251 (7.17%)   21/250 (8.40%) 
Somnolence † 1       
# participants affected / at risk   13/250 (5.20%)   32/251 (12.75%)   40/250 (16.00%) 
Psychiatric disorders       
Insomnia † 1       
# participants affected / at risk   15/250 (6.00%)   14/251 (5.58%)   15/250 (6.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA V. 10.1



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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