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

Neuropathic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01701362
• Other study ID #: A0081279
• Secondary ID: 2012-003304-12
• Status: Completed
• Phase: Phase 3
• Start date: October 2012
• Est. completion date: August 2015

Study information

• Verified date: April 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 542
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain

Intervention

Drug:
• pregabalin
capsules, 150-600 mg/day administered in divided doses twice a day for 15 weeks after randomization
• placebo
capsules, placebo for pregabalin administered in divided doses twice a day for 15 weeks after randomization

Locations

Country	Name	City	State
Bulgaria	MHAT Puls AD	Blagoevgrad
Bulgaria	MHAT "Avis Medika"	Pleven
Bulgaria	MHAT "Sv.Pantaleymon"	Pleven
Bulgaria	DCC Akta Medika Ltd.	Sevlievo
Bulgaria	DCC "Sveta Anna"EOOD	Sofia
Bulgaria	UMHAT Aleksandrovska	Sofia
Canada	Aggarwal and Associates Limited	Brampton	Ontario
Canada	NRK Medical Research Clinic	London	Ontario
Canada	NRK Medical Research Clinic (Adminstrative Office Only)	London	Ontario
Canada	London Road Diagnostic Clinic and Medical Centre	Sarnia	Ontario
Croatia	General Hospital "dr. Ivo Pedisic"	Sisak
Denmark	Glostrup Hospital	Glostrup
Germany	Klinische Forschung Berlin-Mitte GmbH	Berlin
Germany	Synexus Clinical Research GmbH	Berlin
Germany	Synexus Clinical Research GmbH	Bochum
Germany	Praxis für Spezielle Schmerztherapie und Palliativmedizin	Böhlen	Sachsen
Germany	Synexus Clinical Research GmbH	Frankfurt
Germany	Gemeinschaftspraxis für Schmerz- und Psychotherapie	Hamburg
Germany	Klinische Forschung Hamburg GmbH	Hamburg
Germany	Klinische Forschung Hannover-Mitte GmbH	Hannover	Niedersachsen
Germany	pro scientia med im MARE Klinikum	Kiel-Kronshagen	Schleswig-holstein
Germany	medamed GmbH Studienambulanz	Leipzig	Sachsen
Germany	Synexus Clinical Research GmbH	Leipzig
Germany	Klinische Forschung Schwerin GmbH	Schwerin
Hungary	Synexus Magyarorszag Kft.	Budapest
Hungary	UNO Medical Trials Kft	Budapest
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "Przychodnia Morena" Sp. z.o.o.	Gdansk
Poland	"SYNEXUS POLSKA" Sp. z o.o. Oddzial w Gdyni	Gdynia
Poland	"Synexus Polska" Sp. z o.o. Oddzial W Katowicach	Katowice
Poland	Malopolskie Centrum Medyczne S.C.	Krakow
Poland	NZOZ IGNIS dr n. med. Alicja Lobinska	Swidnik
Poland	"SYNEXUS Polska" Sp. z o.o. ODDZIAL W WARSZAWIE	Warszawa
Poland	"SYNEXUS POLSKA" Sp. z o.o. Odzial we Wroclawiu	Wroclaw
Puerto Rico	Ponce School of Medicine, CAIMED Center	Ponce
Romania	Centrul Medical Sana	Bucuresti
Romania	Clubul Sanatatii SRL	Campulung Muscel
Romania	Spitalul Clinic de Neuropsihiatrie Craiova	Craiova
Romania	Spitalul Clinic Municipal Dr. Gavril Curteanu Oradea,Sectia Neurologie I	Oradea
Romania	Spitalul Clinic Judetean de Urgenta Sibiu,Sectia Neurologie	Sibiu
Romania	Spitalul Clinic Judetean de Urgenta Targu-Mures , Sectia Neurologie II	Targu Mures
South Africa	Synexus SA - Stanza Clinical Research Centre	Pretoria	Gauteng
South Africa	Synexus SA - Watermeyer Clinical Research Centre	Pretoria	Gauteng
South Africa	Synexus SA - Roodepoort Medicross Clinical Research Centre	Roodeport	Gauteng
South Africa	Welkom Clinical Trial Centre	Welkom	FREE State
Sweden	Ladulaas Kliniken	Boras
Sweden	CTC, Gothia Forum, Sahlgrenska Universitetssjukhus	Göteborg
Sweden	Probare	Lund
Sweden	Pharmasite	Malmö
Sweden	Bragee Medect AB	Stockholm
United States	Allegheny Pain Management, P.C.	Altoona	Pennsylvania
United States	Michigan Head Pain and Neurological Institute	Ann Arbor	Michigan
United States	Integrated Neurology Services , PLLC	Arlington	Virginia
United States	IntegraTrials, LLC	Arlington	Virginia
United States	Advanced Rx Clinical Research	Artesia	California
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Northern Ohio Neurosciences, LLC	Bellevue	Ohio
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Washington Center for Pain Management LLC	Bellevue	Washington
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Colorado Clinic	Boulder	Colorado
United States	Orthopedic Research Institute	Boynton Beach	Florida
United States	Pharmacorp Clinical Trials, Inc.	Charleston	South Carolina
United States	PMG Research of Charlotte	Charlotte	North Carolina
United States	Chicago Anesthesia Associates	Chicago	Illinois
United States	Rehabilitation Institute of Chicago	Chicago	Illinois
United States	Advance Medical Research	Clearwater	Florida
United States	Innovative Research of West Florida	Clearwater	Florida
United States	TLM Medical Services, LLC	Columbia	South Carolina
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Dallas Pain Consultants	Dallas	Texas
United States	FutureSearch Trials of Dallas, L. P.	Dallas	Texas
United States	Mountain View Clinical Research Inc.	Denver	Colorado
United States	Otri-Med Corporation	Edgewood	Kentucky
United States	Washington Center for Pain Management LLC	Edmonds	Washington
United States	Washington Center for Pain Management LLC	Everett	Washington
United States	St. Luke's Medical Clinic	Fort Collins	Colorado
United States	Behavioral Research Specialists, LLC	Glendale	California
United States	Dedicated Clinical Research	Goodyear	Arizona
United States	Pharmacum Biomedical Research	Greenville	South Carolina
United States	Piedmont Comprehensive Pain Management Group, LLC	Greenville	South Carolina
United States	Aga Clinical Trials	Hialeah	Florida
United States	Health Care Family Rehab & Research Center	Hialeah	Florida
United States	Research in Miami, Inc.	Hialeah	Florida
United States	Homestead Medical Research , Inc.	Homestead	Florida
United States	Abigail R. Neiman, MD, PA	Houston	Texas
United States	Agadadash Kuliev, MD, PA	Houston	Texas
United States	Biopharma Informatic Inc. Research Center	Houston	Texas
United States	Medstar Clinical Research Associates	Houston	Texas
United States	Tennesse Valley Pain Consultants	Huntsville	Alabama
United States	NervePro Medical Corp.	Irvine	California
United States	University of California, Irvine	Irvine	California
United States	Wells Institute for Health Awareness	Kettering	Ohio
United States	New Phase Research and Development	Knoxville	Tennessee
United States	Clinical and Translational Research Institute	La Jolla	California
United States	Alliance Research Centers	Laguna Hills	California
United States	South Orange County Surgical Medical Group	Laguna Hills	California
United States	Centex Studies, Inc	Lake Charles	Louisiana
United States	Center For United Research, Inc.	Lakewood	California
United States	Advanced Biomedical Research of America	Las Vegas	Nevada
United States	Central Kentucky Research Associates, Inc.	Lexington	Kentucky
United States	University of Southern California	Los Angeles	California
United States	USC I.D.S. Pharmacy	Los Angeles	California
United States	Samaritan Center for Medical Research	Los Gatos	California
United States	Georgia Institute for Clinical Research, LLC	Marietta	Georgia
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Florida International Research Center	Miami	Florida
United States	Kendall South Medical Center, Inc.	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	AMPM Research Clinic	Miami Gardens	Florida
United States	North County Clinical Research	Oceanside	California
United States	Cor Clinical Research, Llc	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Heartland Clinical Research, Inc.	Omaha	Nebraska
United States	Quality Clinical Research, Inc.	Omaha	Nebraska
United States	Compass Research, LLC	Orlando	Florida
United States	A-One Family Practice	Ormond Beach	Florida
United States	Aba Family Medicine, LLC	Ormond Beach	Florida
United States	Ribo Research, LLC dba Peninsula Resarch	Ormond Beach	Florida
United States	Kansas City Bone & Joint Clinic	Overland Park	Kansas
United States	CRI Lifetree	Philadelphia	Pennsylvania
United States	Arizona Research Center	Phoenix	Arizona
United States	Elite Clinical Studies, LLC	Phoenix	Arizona
United States	HOPE Research Institute	Phoenix	Arizona
United States	Neuromuscular Research Center	Phoenix	Arizona
United States	The Pain Center of Arizona	Phoenix	Arizona
United States	The Pain Center of Arizona	Phoenix	Arizona
United States	Summit Research Network, Inc.	Portland	Oregon
United States	Washington Center for Pain Management LLC	Renton	Washington
United States	ClinRx Research, LLC	Richardson	Texas
United States	University of Rochester, Translational Pain Research	Rochester	New York
United States	Allied Clinical Research	Roseville	California
United States	Comprehensive Pain Care of South Florida	Royal Palm Beach	Florida
United States	Northern California Research	Sacramento	California
United States	Medex Healthcare Research, Inc.	Saint Louis	Missouri
United States	J. Lewis Research, Inc./Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewish Research, Inc./Foothill Family Clinic South	Salt Lake City	Utah
United States	Lifetree Clinical Research	Salt Lake City	Utah
United States	DCT - Stone Oak, LLC dba Discovery Clinical Trials	San Antonio	Texas
United States	Sarasota Pain Medicine Research	Sarasota	Florida
United States	Sealy Urgent Care Center and Medical Clinic	Sealy	Texas
United States	Summit Research Network (Seattle) LLC	Seattle	Washington
United States	Advanced Internal Medicine, PC	Stockbridge	Georgia
United States	Research 1 Clinical Research Network, Inc. (Administrative Office Only)	Stockbridge	Georgia
United States	Meridien Research	Tampa	Florida
United States	Northwest Ohio Research Center, LLC	Toledo	Ohio
United States	Robert L Kalb, M.D, Inc	Toledo	Ohio
United States	Quality of Life Medical & Research Centers, LLC	Tucson	Arizona
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	Investigational Drug Services, The George Washington University Medical Center	Washington	District of Columbia
United States	The George Washington University Medical Center	Washington	District of Columbia
United States	The George Washington University Medical Center (Department of Neurology)	Washington	District of Columbia
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas
United States	Elite Clinical Trials, Inc.	Wildomar	California
United States	PMG Research of Winston-Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Croatia,  Denmark,  Germany,  Hungary,  Korea, Republic of,  Poland,  Puerto Rico,  Romania,  South Africa,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline Mean Pain Score	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.	Baseline
Primary	Change From Baseline to Week 15 in Weekly Mean Pain Score	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.	up to Week 15
Secondary	Patient Global Impression of Change (PGIC) at 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.	Week 15
Secondary	Change From Baseline in Overall Weekly Mean Sleep Interference Score (SIRS)	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.	up to Week 15
Secondary	Change From Baseline in Pain Severity Index (Brief Pain Inventory-short Form [BPI-sf])	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.	Week 15
Secondary	Change From Baseline in Pain Interference Index (BPI-sf)	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.	Week 15
Secondary	Change From Baseline to Endpoint in Quality of Life Using EuroQol (EQ-5D) Health State Profile Scores	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.	Week 15
Secondary	Baseline Scores in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.	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.	Baseline
Secondary	Mean Change From Baseline in the Medical Outcomes Study Sleep Scale (MOS-SS) - Sub-domain Score.	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.	Week 15
Secondary	Percentage of Participants in MOS-SS With Optimal Sleep Status.	MOS-SS optimal sleep status analyzed on a scale of four parameters: any improvements, no change, any worsening and not applicable.	Week 15
Secondary	Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of =30%.	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.	Week 15
Secondary	Percentage of Responders to Treatment With Pregabalin Measured as Reduction in Mean Pain Score of =50%	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.	Week 15

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