Trial Outcomes & Findings for Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations (NCT NCT00360308)

Last Updated: 2014-07-11

Results Overview

Efficacy assessments were recorded by subjects using a home diary card. 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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

723 participants

Primary outcome timeframe

Baseline and Week 18

Results posted on

2014-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Overall Study STARTED	247	234	242
Overall Study COMPLETED	171	155	154
Overall Study NOT COMPLETED	76	79	88

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Overall Study Adverse Event	15	14	25
Overall Study Abnormal Laboratory Value(s)	0	1	0
Overall Study Protocol Violation	2	1	2
Overall Study Withdrawal by Subject	11	7	14
Overall Study Lack of Efficacy	3	0	2
Overall Study Other	2	1	1
Overall Study Study termination by sponsor	43	55	44

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=247 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone n=234 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel n=242 Participants Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Total n=723 Participants Total of all reporting groups
Age, Customized <65 years	131 participants n=99 Participants	114 participants n=107 Participants	123 participants n=206 Participants	368 participants n=7 Participants
Age, Customized ≥65 years	116 participants n=99 Participants	120 participants n=107 Participants	119 participants n=206 Participants	355 participants n=7 Participants
Sex: Female, Male Female	98 Participants n=99 Participants	98 Participants n=107 Participants	94 Participants n=206 Participants	290 Participants n=7 Participants
Sex: Female, Male Male	149 Participants n=99 Participants	136 Participants n=107 Participants	148 Participants n=206 Participants	433 Participants n=7 Participants
Race/Ethnicity, Customized White	191 participants n=99 Participants	176 participants n=107 Participants	185 participants n=206 Participants	552 participants n=7 Participants
Race/Ethnicity, Customized Asian	55 participants n=99 Participants	57 participants n=107 Participants	57 participants n=206 Participants	169 participants n=7 Participants
Race/Ethnicity, Customized Other	1 participants n=99 Participants	1 participants n=107 Participants	0 participants n=206 Participants	2 participants n=7 Participants

PRIMARY outcome

Timeframe: Baseline and Week 18

Population: The Intent-to-Treat (ITT) Population comprised all randomised patients who took at least one dose of study medication or placebo and who had a valid baseline efficacy measure and at least one post-baseline efficacy measure.

Outcome measures

Outcome measures
Measure	Placebo n=228 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone n=221 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel n=213 Participants Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 18 (Including LOCF Data)	-0.82 Hours Interval -1.16 to -0.48	-1.29 Hours Interval -1.63 to -0.96	-0.92 Hours Interval -1.27 to -0.57

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: ITT Population

Efficacy assessments were recorded by subjects using a home diary card. 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. 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=215 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone n=210 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel n=199 Participants Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Mean Change From Baseline in UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 18 (Including LOCF Data)	-1.42 Scores on a scale Interval -2.04 to -0.8	-2.50 Scores on a scale Interval -3.11 to -1.9	-1.06 Scores on a scale Interval -1.7 to -0.42

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: ITT Population

Efficacy assessments were recorded by subjects using a home diary card. 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=217 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone n=215 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel n=202 Participants Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 18 (Including LOCF Data)	-1.20 Scores on a scale Interval -2.12 to -0.29	-3.08 Scores on a scale Interval -3.97 to -2.19	-1.67 Scores on a scale Interval -2.61 to -0.73

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: ITT Population

Efficacy assessments were recorded by subjects using a home diary card. ON state is when medication is providing benefits to stiffness, slowness, and tremor.

Outcome measures

Outcome measures
Measure	Placebo n=228 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone n=221 Participants Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel n=213 Participants Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 18 (Including LOCF Data)	0.88 Hours Interval 0.52 to 1.24	1.10 Hours Interval 0.74 to 1.46	0.47 Hours Interval 0.1 to 0.84

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 39 other events

Deaths: 0 deaths

Entacapone

Serious events: 8 serious events

Other events: 63 other events

Deaths: 0 deaths

Perampanel

Serious events: 11 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=247 participants at risk Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.	Entacapone n=234 participants at risk Placebo identical to perampanel (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as one entacapone 200 mg dose with each dose of levodopa.	Perampanel n=242 participants at risk Perampanel 2 mg (Weeks 0 to 2 one dose per day, Weeks 2 to 18 two doses per day); as well as a placebo identical to entacapone with each dose of levodopa.
Gastrointestinal disorders Nausea	3.6% 9/247 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	6.8% 16/234 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	3.7% 9/242 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.
Nervous system disorders Dizziness	2.8% 7/247 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	3.8% 9/234 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	8.7% 21/242 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.
Nervous system disorders Dyskinesia	3.2% 8/247 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	11.5% 27/234 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	7.0% 17/242 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.
Nervous system disorders On and Off phenomenon	6.5% 16/247 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	8.1% 19/234 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	7.9% 19/242 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.
Nervous system disorders Somnolence	1.6% 4/247 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	3.4% 8/234 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.	7.0% 17/242 • Adverse events (AEs) were recorded from the time that the participant signed the informed consent form until 30 days after study drug discontinuation and through the termination visit, whichever is longer. All AEs were reported on a case report form (CRF). AEs were recorded on subject diaries and by investigators during clinical visits.

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