Clinical Trial: A Clinical Study in Subjects With Neuropathic Pain From PHN Who Have Had an Inadequate Response to Gabapentin Treatment

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

Official Title: Study PXN110527: The Investigation of the Efficacy and Pharmacokinetics of XP13512 in Subjects With Neuropathic Pain Associated With Post-herpetic Neuralgia (The primary purpose of study PXN110527 was to investigate the efficacy of a high (3600mg/day) dose versus a low (1200mg/day) dose of GEn in subjects with post-herpetic neuralgia (PHN) who have a history of an inadequate response to gabapentin treatment. The study is a cross-over design. Prior to screening subjects are required to have a demonstrated history of an inadequate response (as determined by the investigator) to at least 1800 mg/day of gabapentin. Prior history of treatment with gabapentin includes current treatment at 1800mg/day (2 weeks) or prior treatment with ≥1800mg/day (4 weeks). Subjects could also have been treated with pregabalin monotherapy (150-300mg/day, ≥4 weeks) and had an inadequate response.

Subjects are treated with gabapentin 1800mg/day during the Baseline Period and are randomized if during the Basleline Period they are compliant with gabapentin treatment and have a 24-hour average pain intensity score ≥4.0 based on an 11-point pain intensity numerical rating scale (PI-NRS). Subjects are then randomized to receive gabapentin enacarbil (either 1200mg/day or 3600mg/day in a 1:1 ratio) for Treatment Period 1 (28 days). Followed by a dose of 2400mg/day for 4 days and the alternate fixed dose (either 3600 mg/day or 1200 mg/day) for Treatment Period 2 (28 days).


Sponsor: XenoPort, Inc.

Current Primary Outcome:

  • Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using Last Observation Carried Forward (LOCF) Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Baseline and end of treatment values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (baseline) and the last 7 days on treatment within each period (end of treatment). Participants rated their API over the preceding 24 hours, using an 11-point PI-Numerical Rating Scale (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. Change from baseline was calculated as end of treatment minus baseline. Data are summarized by dose, independent of treatment period.
  • Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data for Each Treatment Period [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Baseline and end of treatment values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (baseline) and the last 7 days on treatment within each period (end of treatment). Participants used a hand-held diary to rate their average pain intensity over the preceding 24 hours, using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. The by period summary is provided as a sensitivity analysis for the primary analysis.


Original Primary Outcome: The mean daily average pain intensity score for the last week of each treatment period based on an 11-point PI-NRS (0 = "no pain" and 10 = "pain as bad as you can imagine").

Current Secondary Outcome:

  • Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Day-time is defined as the time between rising in the morning and going to bed at night. Participants recorded day-time API on a daily basis in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and end of treatment scores are as defined for the primary endpoint. Change from baseline is calculated as the end of treatment score minus the baseline score. An ANCOVA with baseline value, BMI, grouped center as covariates was used. Data are summarized by dose, independent of treatment period.
  • Change From Baseline in the Mean Day-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Day-time worst pain is defined as the participant's assessment of their worst pain intensity between rising in the morning and going to bed at night. Day-time worst pain was recorded in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and end of treatment scores are as defined for the primary endpoint. Change from baseline is calculated as the end of treatment score minus the baseline score. An ANCOVA with baseline value, BMI, grouped center as covariates was used. Data are summarized by dose, independent of treatment period.
  • Change From Baseline in the Mean Current (Evening) Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Current pain is defined as the participant's assessment of pain intensity "right now." Participants recorded their current evening pain intensity in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and end of treatment scores are as defined for the primary endpoint. Change from baseline is calculated as the end of treatment score minus the baseline score. An ANCOVA with baseline value, BMI, grouped center as covariates was used. Data are summarized by dose, independent of treatment period.
  • Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Night-time is defined as the time between going to bed in the evening and rising in the morning. Participants recorded night-time API on a daily basis in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and end of treatment scores are as defined for the primary endpoint. Change from baseline is calculated as the end of treatment score minus the baseline score. An ANCOVA with baseline value, BMI, grouped center as covariates was used. Data are summarized by dose, independent of treatment period.
  • Change From Baseline in the Mean Night-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Night-time worst pain is defined as the participant's assessment of their worst pain intensity between going to bed and rising in the morning. Participants recorded night-time worst pain in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and end of treatment scores are as defined for primary endpoint. Change from baseline = the end of treatment score minus the baseline score. An ANCOVA with baseline value, BMI, grouped center as covariates was used. Data are summarized by dose, independent of treatment period.
  • Change From Baseline in the Mean Current Morning Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Current pain is defined as the participant's assessment of pain intensity "right now." Participants recorded their current morning pain intensity in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and end of treatment scores are as defined for the primary endpoint. Change from baseline is calculated as the end of treatment score minus the baseline score. An ANCOVA with baseline value, BMI, grouped center as covariates was used. Data are summarized by dose, independent of treatment period.
  • Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]
    Baseline and end of treatment (EOT) scores are

    Original Secondary Outcome: 24-hour, Day-time, Night time average pain intensity score; Current pain intensity score; Day-time and Night time worst pain intensity score; Sleep interference score; and Amount of rescue analgesic consumed.

    Information By: XenoPort, Inc.

    Dates:
    Date Received: February 6, 2008
    Date Started: March 2008
    Date Completion:
    Last Updated: July 15, 2013
    Last Verified: January 2013