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

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ClinicalTrials.gov Identifier: NCT00368108
Recruitment Status : Completed
First Posted : August 24, 2006
Results First Posted : February 5, 2013
Last Update Posted : May 20, 2013
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

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
Enrollment 752
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 251 [1] 251 250
Completed 187 198 182
Not Completed 64 53 68
Reason Not Completed
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.
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 250 251 250 751
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 250 participants 251 participants 250 participants 751 participants
<65 years 149 144 147 440
≥ 65 years 101 107 103 311
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 250 participants 251 participants 250 participants 751 participants
Female
86
  34.4%
87
  34.7%
86
  34.4%
259
  34.5%
Male
164
  65.6%
164
  65.3%
164
  65.6%
492
  65.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 250 participants 251 participants 250 participants 751 participants
White 233 239 240 712
Black 4 2 1 7
Asian 5 4 1 10
Other 8 6 8 22
1.Primary Outcome
Title Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 208 213 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Hours
-0.96
(-1.42 to -0.51)
-0.93
(-1.38 to -0.49)
-0.76
(-1.20 to -0.31)
2.Secondary Outcome
Title Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 213 216 211
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a scale
-0.85
(-1.70 to -0.00)
-0.81
(-1.66 to 0.04)
-1.40
(-2.23 to -0.56)
3.Secondary Outcome
Title Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 213 215 210
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Scores on a Scale
-2.15
(-3.59 to -0.71)
-1.69
(-3.13 to -0.25)
-3.29
(-4.71 to -1.87)
4.Secondary Outcome
Title Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 208 213 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Hours
0.73
(0.29 to 1.18)
0.78
(0.33 to 1.22)
0.28
(-0.15 to 0.72)
Time Frame From the time the subject signed the informed consent form to 30 days after the last dose of the study drug.
Adverse Event Reporting Description Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
 
Arm/Group Title Placebo Perampanel 2mg Perampanel 4mg
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Placebo Perampanel 2mg Perampanel 4mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Perampanel 2mg Perampanel 4mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/250 (8.80%)   12/251 (4.78%)   18/250 (7.20%) 
Blood and lymphatic system disorders       
Anaemia  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Cardiac disorders       
Atrial flutter  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Coronary artery disease  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Myocardial infarction  1  2/250 (0.80%)  1/251 (0.40%)  0/250 (0.00%) 
Myocardial ischaemia  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Angina Pectoris  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Cardio-Respiratory arrest  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Coronary artery occlusion  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Gastrointestinal disorders       
Constipation  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Large intestine perforation  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Oesophageal stenosis  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Small intestinal obstruction  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Crohn's disease  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Gastrointestinal haemorrhage  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Rectal haemorrhage  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
General disorders       
Non-cardiac chest pain  1  0/250 (0.00%)  1/251 (0.40%)  1/250 (0.40%) 
Chest pain  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Pain  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Infections and infestations       
Pneumonia  1  2/250 (0.80%)  0/251 (0.00%)  2/250 (0.80%) 
Cellulitis  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Urinary tract infection  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  1/250 (0.40%)  1/251 (0.40%)  1/250 (0.40%) 
Femur fracture  1  1/250 (0.40%)  0/251 (0.00%)  1/250 (0.40%) 
Hip fracture  1  2/250 (0.80%)  0/251 (0.00%)  1/250 (0.40%) 
Wrist fracture  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Joint dislocation  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Stress fracture  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Musculoskeletal and connective tissue disorders       
Pain in extremity  1  1/250 (0.40%)  1/251 (0.40%)  0/250 (0.00%) 
Osteoarthritis  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Melanoma recurrent  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Bile duct cancer  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Prostate cancer  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Nervous system disorders       
Syncope  1  1/250 (0.40%)  1/251 (0.40%)  1/250 (0.40%) 
Cerebrovascular accident  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Memory Impairment  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Myasthenia gravis  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
ON and OFF phenomenon  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Quadriparesis  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Tremor  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Reversible ischaemic neurological deficit  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Tonic convulsion  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Psychiatric disorders       
Confusional state  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Hallucination  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Suicide attempt  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Delirium  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Hallucination, visual  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Major depression  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Micturition urgency  1  1/250 (0.40%)  0/251 (0.00%)  0/250 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  0/250 (0.00%)  0/251 (0.00%)  1/250 (0.40%) 
Surgical and medical procedures       
Hospitalization  1  0/250 (0.00%)  1/251 (0.40%)  0/250 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA V. 10.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Perampanel 2mg Perampanel 4mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   111/250 (44.40%)   110/251 (43.82%)   144/250 (57.60%) 
Gastrointestinal disorders       
Nausea  1  16/250 (6.40%)  11/251 (4.38%)  12/250 (4.80%) 
Infections and infestations       
Urinary Tract Infection  1  10/250 (4.00%)  11/251 (4.38%)  13/250 (5.20%) 
Injury, poisoning and procedural complications       
Fall  1  23/250 (9.20%)  23/251 (9.16%)  19/250 (7.60%) 
Musculoskeletal and connective tissue disorders       
Back Pain  1  7/250 (2.80%)  16/251 (6.37%)  12/250 (4.80%) 
Nervous system disorders       
Balance Disorder  1  3/250 (1.20%)  6/251 (2.39%)  17/250 (6.80%) 
Dizziness  1  14/250 (5.60%)  15/251 (5.98%)  29/250 (11.60%) 
Dyskinesia  1  39/250 (15.60%)  21/251 (8.37%)  43/250 (17.20%) 
Headache  1  18/250 (7.20%)  10/251 (3.98%)  12/250 (4.80%) 
ON and OFF phenomenon  1  24/250 (9.60%)  18/251 (7.17%)  21/250 (8.40%) 
Somnolence  1  13/250 (5.20%)  32/251 (12.75%)  40/250 (16.00%) 
Psychiatric disorders       
Insomnia  1  15/250 (6.00%)  14/251 (5.58%)  15/250 (6.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA V. 10.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Eisai Inc.
Organization: Eisai Call Center
Phone: 888-422-4743
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00368108     History of Changes
Other Study ID Numbers: E2007-A001-302
First Submitted: August 22, 2006
First Posted: August 24, 2006
Results First Submitted: October 23, 2012
Results First Posted: February 5, 2013
Last Update Posted: May 20, 2013