Evaluation of the Long-term Safety, Tolerability, and Efficacy of Perampanel (E2007) as an Adjunctive Therapy in Levodopa Treated Parkinson's Disease Subjects With Motor Fluctuations

• ClinicalTrials.gov Identifier: NCT00505622
• Recruitment Status: Terminated
• First Posted: July 23, 2007
• Results First Posted: November 22, 2012
• Last Update Posted: January 21, 2016
• Sponsor: Eisai Limited
• Information provided by (Responsible Party): Eisai Inc. ( Eisai Limited )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson's Disease
• Intervention: Drug: Perampanel
• Enrollment: 328

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
Arm/Group Description	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.
Period Title: Overall Study
Started	121	108	96
Completed	0	0	0
Not Completed	121	108	96
Reason Not Completed
Adverse Event	5	6	4
Protocol Violation	1	1	0
Withdrawal by Subject	0	3	2
Study termination by sponsor	115	98	90

Baseline Characteristics

Arm/Group Title		Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)	Total
Arm/Group Description		Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Total of all reporting groups
Overall Number of Baseline Participants		121	108	96	325
Baseline Analysis Population Description		[Not Specified]
Age, Customized [1]; Measure Type: Number; Unit of measure: Particpants	Number Analyzed	121 participants	108 participants	96 participants	325 participants
<65		65	52	46	163
>= 65		56	56	50	162
		[1] Measure Description: Data comes from previous double-blind core study (E2007-G000-309). Safety Population.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	121 participants	108 participants	96 participants	325 participants
	Female	46 38.0%	44 40.7%	30 31.3%	120 36.9%
	Male	75 62.0%	64 59.3%	66 68.8%	205 63.1%
		[1] Measure Description: Data comes from previous double-blind core study (E2007-G000-309). Safety Population - All subjects entering the open-label extension study who took at least 1 dose of perampanel.
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	121 participants	108 participants	96 participants	325 participants
White		92	75	65	232
Asian		29	33	31	93
		[1] Measure Description: This baseline characteristic is for Race. Data comes from previous double-blind core study (E2007-G000-309). Safety Population.

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Total Daily OFF Time (Hours) During Open-label Extension Study
Description	OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor. All data was collected using a 3-day diary within a window of a defined visit.
Time Frame	Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up

Outcome Measure Data

Analysis Population Description

Safety Population - All subjects entering the open-label extension study who took at least 1 dose of perampanel.

Arm/Group Title	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
Arm/Group Description:	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.
Overall Number of Participants Analyzed	121	108	96
Mean (Standard Deviation); Unit of Measure: Hours
Week 0	-1.03 (2.635)	-1.07 (2.595)	-1.24 (2.643)
Week 2	-0.91 (2.323)	-1.28 (2.867)	-1.31 (2.779)
Week 4	-0.65 (2.945)	-1.15 (2.010)	-1.67 (2.438)
Week 8	-0.70 (2.983)	-1.16 (2.509)	-1.36 (2.324)
Week 20	-1.34 (2.972)	-1.14 (1.805)	-2.11 (2.163)
Follow-up	-0.77 (2.983)	-1.61 (2.435)	-0.94 (2.978)

2. Secondary Outcome

Title	Mean Change From Baseline in UPDRS Part II (ADL) Score in OFF State (Hours) During Open-label Extension Study
Description	Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. 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. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Time Frame	Baseline, Week 0, Week 20, Week 32

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
Arm/Group Description:	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.
Overall Number of Participants Analyzed	121	108	96
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Week 0	-0.84 (4.241)	-1.99 (4.469)	-1.66 (4.598)
Week 20	-0.12 (4.727)	-2.82 (4.086)	-2.66 (4.972)
Week 32	1.11 (2.667)	0.60 (2.408)	-0.67 (3.141)

3. Secondary Outcome

Title	Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) During Open-label Extension Study
Description	Unified Parkinson's Disease Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of Parkinson's Disease. 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, Week 0, Week 20, Week 32

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
Arm/Group Description:	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.
Overall Number of Participants Analyzed	121	108	96
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Week 0	-0.25 (6.874)	-0.64 (6.911)	-0.96 (6.999)
Week 20	0.30 (7.463)	-0.53 (6.950)	-1.63 (8.005)
Week 32	2.22 (5.869)	-2.00 (5.523)	7.17 (6.463)

4. Secondary Outcome

Title	Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) During Open-label Extension Study
Description	ON state is when medication is providing benefits with regard to stiffness, slowness, and tremor. All data was collected using a 3-day diary within a window of a defined visit.
Time Frame	Baseline, Week 0, Week 2, Week 4, Week 8, Week 20, Follow-up

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
Arm/Group Description:	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.
Overall Number of Participants Analyzed	121	108	96
Mean (Standard Deviation); Unit of Measure: Hours
Week 0	1.08 (2.820)	0.58 (3.004)	0.48 (2.773)
Week 2	0.30 (2.776)	0.80 (2.731)	0.91 (2.940)
Week 4	0.38 (2.825)	0.43 (2.091)	1.24 (2.724)
Week 8	0.17 (3.099)	0.52 (2.542)	0.73 (2.261)
Week 20	0.94 (3.535)	0.82 (2.231)	1.62 (2.351)
Follow-up	0.43 (3.368)	1.12 (2.561)	0.85 (3.497)

Adverse Events

Time Frame	Adverse events (AEs) were defined as treatment emergent in this study if the start date of the event was on or after the start of study medication in this study. Adverse events that occurred 30 days after the last dose of study drug were 'post-treatment'.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
Arm/Group Description	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.	Subjects entered this open-label extension study from the double-blind core study (E2007-G000-309). Subjects started on perampanel 2mg once daily for 2 weeks, followed by 4mg once daily for 2 weeks (Titration Phase); Subjects then continued onto the maintenance phase of perampanel 4mg once daily for 2 weeks. Subjects who did not tolerate the study drug at 4mg were allowed to down-titrate to 2mg. Subjects who did not tolerate 2mg were withdrawn from the study.
All-Cause Mortality
	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/121 (1.65%)	6/108 (5.56%)	2/96 (2.08%)
Cardiac disorders
Angina Pectoris † 1	0/121 (0.00%)	1/108 (0.93%)	0/96 (0.00%)
General disorders
Chest Pain † 1	0/121 (0.00%)	0/108 (0.00%)	1/96 (1.04%)
Nervous system disorders
Dementia † 1	0/121 (0.00%)	1/108 (0.93%)	0/96 (0.00%)
Parkinson's Disease † 1	1/121 (0.83%)	0/108 (0.00%)	0/96 (0.00%)
Radicular Syndrome † 1	0/121 (0.00%)	1/108 (0.93%)	0/96 (0.00%)
Transient Ischaemic Attack † 1	0/121 (0.00%)	1/108 (0.93%)	0/96 (0.00%)
Psychiatric disorders
Hallucination † 1	0/121 (0.00%)	1/108 (0.93%)	0/96 (0.00%)
Renal and urinary disorders
Nephrolithiasis † 1	1/121 (0.83%)	0/108 (0.00%)	0/96 (0.00%)
Reproductive system and breast disorders
Uterine Prolapse † 1	0/121 (0.00%)	0/108 (0.00%)	1/96 (1.04%)
Vascular disorders
Hypotension † 1	0/121 (0.00%)	1/108 (0.93%)	0/96 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA v.11
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Perampanel (Placebo During Core Study)	Perampanel (Entacapone 200mg During Core Study)	Perampanel (Perampanel 4mg During Core Study)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	27/121 (22.31%)	27/108 (25.00%)	17/96 (17.71%)
Nervous system disorders
Dizziness † 1	8/121 (6.61%)	3/108 (2.78%)	4/96 (4.17%)
Dyskinesia † 1	4/121 (3.31%)	6/108 (5.56%)	5/96 (5.21%)
On and Off Phenomenon † 1	9/121 (7.44%)	12/108 (11.11%)	6/96 (6.25%)
Parkinson's Disease † 1	7/121 (5.79%)	3/108 (2.78%)	1/96 (1.04%)
Somnolence † 1	4/121 (3.31%)	6/108 (5.56%)	3/96 (3.13%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA v.11

Limitations and Caveats

Due to early termination, no subjects completed this open-label extension study.

More Information

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. ( Eisai Limited )
• ClinicalTrials.gov Identifier: NCT00505622
• Other Study ID Numbers: E2007-G000-318; 2007-000801-30 ( EudraCT Number )
• First Submitted: July 9, 2007
• First Posted: July 23, 2007
• Results First Submitted: October 23, 2012
• Results First Posted: November 22, 2012
• Last Update Posted: January 21, 2016