Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations (NCT NCT00368108)

Last Updated: 2013-05-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

752 participants

Primary outcome timeframe

Baseline and Week 20

Results posted on

2013-05-20

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	251	251	250
Overall Study COMPLETED	187	198	182
Overall Study NOT COMPLETED	64	53	68

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	38	26	44
Overall Study Abnormal Laboratory Value	0	0	3
Overall Study Protocol Violation	5	9	9
Overall Study Withdrawal by Subject	9	3	5
Overall Study Lack of Efficacy	7	8	5
Overall Study Physician Decision	2	0	1
Overall Study Other	3	7	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=250 Participants 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 n=251 Participants 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 n=250 Participants 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 n=751 Participants Total of all reporting groups
Age, Customized <65 years	149 Participants n=5 Participants	144 Participants n=7 Participants	147 Participants n=5 Participants	440 Participants n=4 Participants
Age, Customized ≥ 65 years	101 Participants n=5 Participants	107 Participants n=7 Participants	103 Participants n=5 Participants	311 Participants n=4 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	87 Participants n=7 Participants	86 Participants n=5 Participants	259 Participants n=4 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	164 Participants n=7 Participants	164 Participants n=5 Participants	492 Participants n=4 Participants
Race/Ethnicity, Customized White	233 Participants n=5 Participants	239 Participants n=7 Participants	240 Participants n=5 Participants	712 Participants n=4 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	22 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 20

Population: 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).

Outcome measures

Outcome measures
Measure	Placebo n=208 Participants 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 n=213 Participants 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 n=201 Participants 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.
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 20 (Including Last Observation Carried Forward [LOCF] Data)	-0.96 Hours Interval -1.42 to -0.51	-0.93 Hours Interval -1.38 to -0.49	-0.76 Hours Interval -1.2 to -0.31

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=213 Participants 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 n=216 Participants 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 n=211 Participants 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.
Mean Change From Baseline in Scale UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 20 (Including LOCF Data)	-0.85 Scores on a scale Interval -1.7 to 0.0	-0.81 Scores on a scale Interval -1.66 to 0.04	-1.40 Scores on a scale Interval -2.23 to -0.56

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=213 Participants 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 n=215 Participants 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 n=210 Participants 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.
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 20 (Including LOCF Data)	-2.15 Scores on a Scale Interval -3.59 to -0.71	-1.69 Scores on a Scale Interval -3.13 to -0.25	-3.29 Scores on a Scale Interval -4.71 to -1.87

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	Placebo n=208 Participants 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 n=213 Participants 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 n=201 Participants 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.
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 20 (Including LOCF Data)	0.73 Hours Interval 0.29 to 1.18	0.78 Hours Interval 0.33 to 1.22	0.28 Hours Interval -0.15 to 0.72

Adverse Events

Placebo

Serious events: 22 serious events

Other events: 111 other events

Deaths: 0 deaths

Perampanel 2mg

Serious events: 12 serious events

Other events: 110 other events

Deaths: 0 deaths

Perampanel 4mg

Serious events: 18 serious events

Other events: 144 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=250 participants at risk 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 n=251 participants at risk 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 n=250 participants at risk 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.
Gastrointestinal disorders Nausea	6.4% 16/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	4.4% 11/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	4.8% 12/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Infections and infestations Urinary Tract Infection	4.0% 10/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	4.4% 11/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	5.2% 13/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Injury, poisoning and procedural complications Fall	9.2% 23/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	9.2% 23/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	7.6% 19/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Musculoskeletal and connective tissue disorders Back Pain	2.8% 7/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	6.4% 16/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	4.8% 12/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Nervous system disorders Balance Disorder	1.2% 3/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	2.4% 6/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	6.8% 17/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Nervous system disorders Dizziness	5.6% 14/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	6.0% 15/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	11.6% 29/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Nervous system disorders Dyskinesia	15.6% 39/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	8.4% 21/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	17.2% 43/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Nervous system disorders Headache	7.2% 18/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	4.0% 10/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	4.8% 12/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Nervous system disorders ON and OFF phenomenon	9.6% 24/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	7.2% 18/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	8.4% 21/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Nervous system disorders Somnolence	5.2% 13/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	12.7% 32/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	16.0% 40/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Psychiatric disorders Insomnia	6.0% 15/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	5.6% 14/251 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.	6.0% 15/250 • From the time the subject signed the informed consent form to 30 days after the last dose of the study drug. Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.

Additional Information

Eisai Inc.

Eisai Call Center

Phone: 888-422-4743

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place