Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Placebo-controlled Safety and Efficacy Study of Pregabalin in Subjects With Post-traumatic Peripheral Neuropathic Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01701362
Recruitment Status : Completed
First Posted : October 5, 2012
Results First Posted : June 7, 2017
Last Update Posted : June 7, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 3, 2012
First Posted Date  ICMJE October 5, 2012
Results First Submitted Date  ICMJE July 20, 2016
Results First Posted Date  ICMJE June 7, 2017
Last Update Posted Date June 7, 2017
Study Start Date  ICMJE October 2012
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
  • Baseline Mean Pain Score [ Time Frame: Baseline ]
    This is based on the daily pain dairy and is defined as the baseline mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10.
  • Change From Baseline to Week 15 in Weekly Mean Pain Score [ Time Frame: up to Week 15 ]
    This is based on the daily pain diary and is defined as the change from baseline to week 15 in mean pain diary score. The Daily Pain Diary consists of an 11-point numeric rating scale (NRS) ranging from 0 ("no pain") to 10 ("worst possible pain"). Subjects describe their pain during the past 24 hours by choosing the appropriate number between 0 and 10.
Original Primary Outcome Measures  ICMJE
 (submitted: October 3, 2012)
Change from baseline to Week 15 (endpoint) mean pain score. [ Time Frame: Baseline, Week 15 ]
Change History Complete list of historical versions of study NCT01701362 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
  • Patient Global Impression of Change (PGIC) at Week 15 [ Time Frame: Week 15 ]
    A self administered instrument that measures changes in participants' overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). The PGIC is based on the Clinical Global Impression of Change, which is a validated scale.
  • Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS) [ Time Frame: up to Week 15 ]
    This is an 11-point NRS ranging from 0 ("pain does not interfere with sleep") to 10 ("pain completely interferes with sleep" [unable to sleep due to pain]). Participants describe how pain has interfered with their sleep during the past 24 hours. Please note that the data for Baseline (raw scores) have been included in the below table to read the change from Baseline data in context. Note: Weekly mean SIRS scores were derived from the daily sleep diary and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean SIRS scores were defined as the mean of the 7 daily diary SIRS scores from Day 2+7 (n-1) to Day 1+7*n. For participants with multiple diary scores collected on the same day, the average of all non-missing scores for that day was used in any analyses or data listings. "Overall" is the pooled average sleep interference score for each subject across all post-baseline/randomization weeks.
  • Change From Baseline in Pain Severity Index (Brief Pain Inventory-short Form [BPI-sf]) [ Time Frame: Week 15 ]
    A self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. The BPI-sf consists of 5 questions. Four items measure pain on 11-point response scales from 0 (No Pain) to 10 (Pain as bad as you can imagine). In the above scale, score 0 indicates the better outcome whereas score 10 indicates the worse outcome.
  • Change From Baseline in Pain Interference Index (BPI-sf) [ Time Frame: Week 15 ]
    BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24 hour period prior to evaluation. It consists of 7 sub-questions that evaluates the level of pain interference with daily functioning on 11-point response scales from 0 (does not interfere) to 10 (completely interferes). The BPI-sf pain interference index was calculated as average of the seven individual pain interference scores.
  • Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores [ Time Frame: Week 15 ]
    A self-administered questionnaire designed to assess health related quality of life in terms of a single index value or utility score. There are 5 dimensions: mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression. Each dimension is rated on a 3 point response scale and the scores are combined to form a single index value between 0 and 1 with higher scores being more positive (better health status). The EQ-5D was completed by the subject at week-0 and week-15/ET where 30% responder and 50% responder status would be defined for each participants based on the percent change from baseline (week 0/Randomization) to each visit week in mean pain score and participant global impression of change (PGIC). PGIC is a self-administered instrument that measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). It is based on the Clinical Global Impression of Change CGIC), which is a validated scale.
  • Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score. [ Time Frame: Baseline ]
    MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours.
  • Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score. [ Time Frame: Week 15 ]
    MOS-SS is a self administered measure consisting of twelve items that assess the key constructs of sleep. Instrument scored results in 7 subscales: sleep disturbance, snoring, awaken short of breath or with headache, quantity of sleep, optimal sleep, sleep adequacy, somnolence. Two index measures that assess sleep disturbance was also constructed to provide composite scores. Sleep disturbance, snoring, somnolence, awaken short of breath, and the 9 items sleep problems index all have score ranges from 0 (no sleep problems) to 100 (greater sleep problems), therefore a negative change indicates improvement. Sleep adequacy is scored 0 (least sleep adequacy) to 100 (better sleep adequacy), therefore a positive change indicates improvement. Quantity of sleep is scored 0 (less quantity of sleep) to 24 (greater quantity of sleep), therefore a positive change indicates improvement. Optimal sleep is scored Yes if average hours of sleep is in range of 7-8 hours.
  • Percentage of Participants in MOS-SS With Optimal Sleep Status. [ Time Frame: Week 15 ]
    MOS-SS optimal sleep status analyzed on a scale of four parameters: any improvements, no change, any worsening and not applicable.
  • Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥30%. [ Time Frame: Week 15 ]
    Participants with at least 30% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain.
  • Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of ≥50% [ Time Frame: Week 15 ]
    Participants with at least 50% reduction in the mean pain score from baseline to each week. Weekly mean pain NRS scores are derived from the daily pain NRS and calculated as the mean of the available scores in the 7 days. Generally, week 'n' mean pain score is defined as the mean of the 7 daily diary pain ratings from Day 2+7*(n-1) to Day 1+7*n. At least 4 entries within the last 7 days are required to calculate a mean score. Scores range from 0 (no pain) to 10 (worst possible pain), with higher scored indicating increased pain.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2012)
  • Patient Global Impression of Pain (PGIC) [ Time Frame: Week 15 ]
  • Change from baseline to Week 1 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 1 ]
  • Change from baseline to Week 2 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 2 ]
  • Change from baseline to Week 3 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 3 ]
  • Change from baseline to Week 4 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 4 ]
  • Change from baseline to Week 5 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 5 ]
  • Change from baseline to Week 6 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 6 ]
  • Change from baseline to Week 7 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 7 ]
  • Change from baseline to Week 8 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 8 ]
  • Change from baseline to Week 9 mean pain score derived from the subject's daily pain diary [ Time Frame: Basline, Week 9 ]
  • Change from baseline to Week 10 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 10 ]
  • Change from baseline to Week 11 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 11 ]
  • Change from baseline to Week 12 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 12 ]
  • Change from baseline to Week 13 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 13 ]
  • Change from baseline to Week 14 mean pain score derived from the subject's daily pain diary [ Time Frame: Baseline, Week 14 ]
  • Change from baseline to Week 1 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 1 ]
  • Change from baseline to Week 2 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 2 ]
  • Change from baseline to Week 3 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 3 ]
  • Change from baseline to Week 4 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 4 ]
  • Change from baseline to Week 5 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 5 ]
  • Change from baseline to Week 6 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 6 ]
  • Change from baseline to Week 7 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 7 ]
  • Change from baseline to Week 8 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 8 ]
  • Change from baseline to Week 9 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 9 ]
  • Change from baseline to Week 10 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 10 ]
  • Change from baseline to Week 11 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 11 ]
  • Change from baseline to Week 12 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 12 ]
  • Change from baseline to Week 13 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 13 ]
  • Change from baseline to Week 14 mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 14 ]
  • Change from baseline to endpoint (Week 15) mean sleep interference score from the subject's daily sleep diary [ Time Frame: Baseline, Week 15 ]
  • Change from baseline to endpoint (Week 15) in the Medical Outcomes Study (MOS) Sleep Scale total score [ Time Frame: Baseline, Week 15 ]
  • Change from baseline to endpoint (Week 15) in the Medical Outcomes Study (MOS) Sleep Scale for each domain [ Time Frame: Baseline, Week 15 ]
  • Change from baseline to endpoint (Week 15) in the Pain Severity Index derived from the Brief Pain Inventory (BPI-sf) [ Time Frame: Baseline, Week 15 ]
  • Change from baseline to endpoint (Week 15) in the Pain Interference Index derived from the Brief Pain Inventory (BPI-sf) [ Time Frame: Baselin, Week 15 ]
  • Change from baseline to endpoint (Week 15) in the quality of life using the EuroQol (EQ-5D) Health State Profile scores [ Time Frame: Baseline, Week 15 ]
  • Treatment response in pregabalin and placebo arms: Reduction in endpoint (Week 15) mean pain of greater than or equal to 30% [ Time Frame: Baseline, Week 15 ]
  • Treatment response in pregabalin and placebo arms: Reduction in endpoint (Week 15) mean pain of greater than or equal to 50% [ Time Frame: Baseline, Week 15 ]
  • Summarization of Healthcare Utilization Economic Assessment at baseline and endpoint (Week 15) [ Time Frame: Baseline, Week 15 ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at screening [ Time Frame: Screening ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at baseline [ Time Frame: Baseline ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at Week 3 [ Time Frame: Week 3 ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 [ Time Frame: Week 6 ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at Week 9 [ Time Frame: Week 9 ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at Week 12 [ Time Frame: Week 12 ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at endpoint (Week 15) [ Time Frame: Week 15 ]
  • Neurological examination including a neuropathic pain assessment at screening [ Time Frame: Screening ]
  • Neurological examination at endpoint (Week 15) [ Time Frame: Week 15 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Placebo-controlled Safety and Efficacy Study of Pregabalin in Subjects With Post-traumatic Peripheral Neuropathic Pain
Official Title  ICMJE A Randomized Double Blind Placebo Controlled Parallel Group Study Of The Efficacy And Safety Of Pregabalin (Bid) In Subjects With Post-traumatic Peripheral Neuropathic Pain
Brief Summary This study is designed to investigate if pregabalin is effective in treating neuropathic (nerve) pain resulting from peripheral nerve trauma due to a traumatic or surgical event such as, for example, motor vehicle accident, fall, sports injury, knee or hip replacement, hernia repair, thoracotomy, mastectomy, focal/localized burns or crush injury.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Neuropathic Pain
Intervention  ICMJE
  • Drug: pregabalin
    capsules, 150-600 mg/day administered in divided doses twice a day for 15 weeks after randomization
    Other Name: Lyrica, PD-144723
  • Drug: placebo
    capsules, placebo for pregabalin administered in divided doses twice a day for 15 weeks after randomization
Study Arms  ICMJE
  • Active Comparator: pregabalin
    Intervention: Drug: pregabalin
  • Placebo Comparator: placebo
    Intervention: Drug: placebo
Publications * Markman J, Resnick M, Greenberg S, Katz N, Yang R, Scavone J, Whalen E, Gregorian G, Parsons B, Knapp L. Efficacy of pregabalin in post-traumatic peripheral neuropathic pain: a randomized, double-blind, placebo-controlled phase 3 trial. J Neurol. 2018 Dec;265(12):2815-2824. doi: 10.1007/s00415-018-9063-9. Epub 2018 Sep 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 4, 2017)
542
Original Estimated Enrollment  ICMJE
 (submitted: October 3, 2012)
470
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must have chronic peripheral neuropathic pain present for than 6 months after a traumatic or surgical event such as, for example, motor vehicle accident, fall, sports injury, knee or hip replacement, hernia repair, thoracotomy, mastectomy, focal/localized burns or crush injury.
  • Subjects must be literate and have the ability (unaided) to understand and use the interactive voice response system (IVRS), have daily access to a telephone in order to complete the IVRS assessments each day, perform telephone visits and complete all required assessments/forms.
  • Subjects must have sufficient post-traumatic neuropathic pain at screening and baseline.

Exclusion Criteria:

  • Subjects with neuropathic pain due to diabetic peripheral neuropathy (DPN), post herpetic neuralgia (PHN), HIV, trigeminal neuralgia (TGN), carpal tunnel syndrome (CTS) or with central neuropathic pain (for example, due to spinal cord injury) or with Complex Regional Pain Syndrome (CRPS, Type I or Type II).
  • Subjects with other pain that may confound assessment or self-evaluation of the peripheral neuropathic pain.
  • Subjects who have failed pregabalin treatment due to lack of efficacy with an adequate course of therapy at doses greater than or equal to 150 mg/day, who have previously participated in a pregabalin clinical trial or who have been treated with pregabalin at any time during the 6 month period prior to screening.
  • Subjects with epilepsy; pernicious anemia; hematological illnesses; known HIV infection; any clinically unstable cardiovascular (including a myocardial infarction [heart attack] in the 3 months prior to screening), hematological, autoimmune, endocrine, renal, hepatic (including chronic hepatitis B, hepatitis B within the 3 months prior to screening) respiratory, or gastrointestinal disease; symptomatic peripheral vascular disease including intermittent claudication; uncontrolled diabetes mellitus; untreated hypothyroidism.
  • Subjects with a diagnosis of DSM-IV TR Axis I disorder (including, for example, schizophrenia, bipolar disorder) with the exceptions of Generalized Anxiety Disorder (GAD) or major depression that is clinically stable.
  • Subjects considered at risk of suicide or self-harm based on investigator judgment and/or details of a risk assessment.
  • Use of prohibited medications in the absence of appropriate washout periods.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   Croatia,   Denmark,   Germany,   Hungary,   Korea, Republic of,   Poland,   Puerto Rico,   Romania,   South Africa,   Sweden,   United States
Removed Location Countries Israel
 
Administrative Information
NCT Number  ICMJE NCT01701362
Other Study ID Numbers  ICMJE A0081279
2012-003304-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP