An Evaluation of the Efficacy and Safety of E2007 in Patients With Painful Diabetic Neuropathy

Phase 2

Completed

Conditions: Diabetic Neuropathy

Interventions: Drug: E2007 (2 mg)
Drug: E2007 (4 mg)
Drug: Placebo
Drug: E2007 (6 mg)
Drug: E2007 (8 mg)

Registration Number: NCT00505284

Lead Sponsor: Eisai Inc.

Brief Summary: The purpose of this study is to determine the efficacy and safety of Perampanel in patients with painful diabetic neuropathy.

Detailed Description: This is a randomized, double-blind, placebo-controlled, parallel-group study. This is a 5-arm, 21-week study comprised of up to a 2-week Screening period, a 15-week Dose-Escalation and Maintenance Phase using 4 doses of E2007 (2 mg, 4 mg, 6 mg, and 8 mg) or placebo, and a 4-week, single-blind placebo Follow-Up Phase. Patients will be randomly assigned to one of the five treatment groups. Those patients assigned to receive either 4 mg, 6 mg, or 8 mg E2007 will be escalated to the appropriate dose according to an escalation schedule. All patients will take four identical-looking tablets on a daily basis for the entire study duration for blinding purposes.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 352

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Perampanel 2mg	E2007 (2 mg)	-
Perampanel 4mg	E2007 (4 mg)	-
Placebo	Placebo	-
Perampanel 6mg	E2007 (6 mg)	-
Perampanel 8mg	E2007 (8 mg)	-

Primary Outcome Measures

Name	Time	Method
Change in Average Pain Scores From Baseline to Week 15/End of Treatment (EOT)	Baseline to Week 15/EOT	Average of last 7 available scores prior to the visit, based on 11-point Likert-type numerical rating scale for pain (0=no pain, to 10=worst possible pain). This is based on a modified baseline observation carried forward (BOCF).
Responder Rate: Analysis of the Change in Pain Score From Baseline to Week 15/EOT in Subjects Who Had at Least a 30% Reduction in Pain Score	Baseline to Week 15/EOT	Average pain scores were calculated as the average of last 7 available scores prior to the visit, based on 11-point Likert-type numerical rating scale for pain (0=no pain, to 10=worst possible pain). This is based on a modified BOCF.
Responder Rate: Analysis of the Change in Pain Score From Baseline to Week 15/EOT in Subjects Who Had at Least a 50% Reduction in Pain Score	Baseline to Week 15/EOT	Average pain scores were calculated as the average of last 7 available scores prior to the visit, based on 11-point Likert-type numerical rating scale for pain (0=no pain, to 10=worst possible pain). This is based on a modified BOCF.
Mean Change in Average Pain Scores From Baseline at Each Study Week	Baseline, Week 1 to Week 17	Average pain scores were calculated as the average of last 7 available scores prior to the visit, based on 11-point Likert-type numerical rating scale for pain (0=no pain, to 10=worst possible pain). Last on-treatment value refers to last 7 days of available diary data while subject was on double-blind study drug.

Secondary Outcome Measures

Name	Time	Method
Change in Average Sleep Interference Scores From Baseline to Week 15/EOT	Baseline to Week 15/EOT	Average of last 7 available scores prior to the visit, based on 11-point Likert-type numerical rating scale for sleep interference (0=pain did not interfere with sleep, to 10=pain completely interfered with sleep \[unable to sleep\]). Based on modified BOCF.
Change in Short Form - McGill Pain Questionnaire (SF-MPQ) From Baseline to Week 15/EOT	Baseline and Week 15/EOT	SF-MPQ sensory score = sum of intensity scores for descriptors 1-11 (throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, splitting). Each descriptor scored as 0=none, 1=mild, 2=moderate, or 3=severe. Range of possible sensory scores, 0 to 33, with a score of 33 being the most severe intensity.
Analysis of Patient Global Impression of Change (PGIC) at Week 15/EOT	Week 15/EOT	At the EOT (Visit 7) or Early Withdrawal Visit (as appropriate), the subject assessed his/her status compared to how they felt before entering the study. This assessment included an evaluation of pain frequency and intensity, the occurrence of AEs, and overall functional status using a 7-point scale where 1=very much improved and 7=very much worse. Using Modified BOCF.
Change From Baseline to Week 15/EOT in SF-36 Physical and Mental Component Scores	Baseline and Week 15/EOT	Short Form 36 Health Survey Questionnaire (SF-36) measuring limitations in Physical Components including physical activities, usual role activities (due to physical problems), measuring bodily pain, general health perceptions, and Mental Components including social activities, usual role activities (due to emotional problems), vitality (energy and fatigue. Each of the 8 domains are described by a score ranging from 0 to 100, for a range of total possible scores of 0-400 for physical and 0-400 for mental. Higher scores reflect better subject status.
Change From Baseline to Week 15/EOT in Hospital Anxiety and Depression Scale (HADS) Anxiety and Depression Subscale Scores	Baseline and Week 15/EOT	HADS anxiety subscale score=sum of scores for 7 anxiety items, each scored on a 4-pt scale (0, 1, 2, or 3), where a higher score indicates worse anxiety. Range of possible HADS anxiety subscale scores, 0 to 21. HADS depression subscale score=sum of scores for 7 depression items, each scored on a 4-pt scale (0, 1, 2, or 3), where a higher score indicates worse depression. Range of possible HADS depression subscale scores, 0 to 21.
Withdrawal Due to Treatment Failure During Double-Blind Dosing Period	Baseline and Week 15	Based on data reported on the End of Study case report form (CRF): If a subject terminated the study early during the Double-blind Dosing Period due to 'lack of therapeutic efficacy,' the subject was counted as a withdrawal due to treatment failure.
Presence or Absence of Allodynia at Week 15/EOT	Week 15/EOT	Investigators rated subjects' allodynia as mild, moderate, severe, or not present. The presence of allodynia (yes/no) at Week 15/EOT was analyzed.
Analysis of Rescue Analgesic Medication Use (Acetaminophen) During Double-Blind Dosing Period	Baseline to Week 15	If acetaminophen was not reported on the Pain Therapy CRF or on the Concomitant Medication CRF, it was assumed that the subject did not use rescue analgesic medication.