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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of E2007 in Patients With Painful Diabetic Neuropathy

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

Detailed Summary: 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.
Sponsor: Eisai Inc.

Current Primary Outcome:

  • Change in Average Pain Scores From Baseline to Week 15/End of Treatment (EOT) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 d

    Original Primary Outcome: A 24-hour daily pain intensity score, captured on an 11-point Likert-type numeric rating scale using a daily patient diary where 0 represents no pain and 10 represents the worst imaginable pain.

    Current Secondary Outcome:

    • Change in Average Sleep Interference Scores From Baseline to Week 15/EOT [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.


    Original Secondary Outcome: "Responder" analysis of change in pain score from baseline to endpoint; mean pain score for each week; change in mean pain score from baseline at each week. Also, adverse events, laboratory parameters, vital signs, 12-lead ECG and NCV.

    Information By: Eisai Inc.

    Dates:
    Date Received: July 20, 2007
    Date Started: June 2007
    Date Completion:
    Last Updated: June 26, 2014
    Last Verified: February 2013