Study in Neuropathic Pain Patients With Peripheral Nerve Injury

NCT00969059 | Completed Phase 2

• 1 other identifier: 112967
• Study Type: interventional
• Target: 168
• Locations: 7 countries
• Sites: 23

Brief Summary

This study will be a double-blind, placebo-controlled, parallel group study. After enrolment and initial assessments, subjects will receive oral GW856553 7.5 milligram (mg) twice daily (BID) or matching placebo for 28 days in a 1:1 ratio. Sufficient numbers of subjects will be recruited to obtain 142 evaluable subjects. This is a double-blind, randomized, placebo-controlled, parallel group study. Subjects will undertake a screening period which may last up to approximately 3 weeks, followed by a baseline period of 1 week, a randomized treatment period of 4 weeks and a follow-up period of approximately 2 weeks. This is a multi-centre, double-blind, randomized, placebo-controlled study in subjects who have at least moderate intensity of neuropathic pain resulting from peripheral nerve injury due to trauma or surgery. It will investigate the efficacy, safety and tolerability of GW856553 over 28 days of treatment. Approximately 158 subjects will be randomized to ensure 142 evaluable subjects. Randomization ratio will be 1:1 for placebo or GW856553 respectively. The dose of GW856553 will be 7.5 mg BID.

Conditions

Pain, Neuropathic

Keywords

peripheral nerve injury; p38 kinase inhibitor; neuropathic pain

Outcome Measures

Primary Outcomes (1)

• Change in average daily pain score from baseline to Week 4 of treatment based on the 11 point Pain Intensity Numerical Rating Scale (PI-NRS)

  The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Participants rated the pain intensity for the neuropathic pain associated with the nerve injury and not pain from other concomitant causes. Change from baseline was calculated as endpoint value minus the baseline value.

  Baseline (Day -7) and Week 4

Secondary Outcomes (13)

• Change in average daily pain score from baseline to Weeks 1, 2 and 3 of treatment and the week before the follow-up visit

  Baseline (Day -7) and up to Week 3

• Change from baseline in intensity of Dynamic Allodynia at Days 14 and 28 of treatment

  Baseline (Day -7) and Day 14, 28

• Change from baseline in intensity of static hyperalgesia at Days 14 and 28 of treatment

  Baseline (Day -7) and Day 14, 28

• Change from baseline in pain quality on the Short-Form McGill Pain Questionnaire (SF-MPQ) at Days 14 and 28 of treatment and the follow-up visit

  Baseline (Day -7) and Day 14, 28

• Change from baseline in Galer Neuropathic Pain Scale to Days 14 and 28 of treatment and the follow-up visit

  Baseline (Day -7), Day 14, 28 and follow-up (within approximately 14 days post Week 4)

Study Arms (2)

PLACEBO

PLACEBO COMPARATOR

Eligible participant with at least moderate intensity of pain (an average daily pain score of ≥ 4 on the 11 point PI-NRS at baseline) will receive placebo for 28 days.

Drug: PLACEBO

Active

EXPERIMENTAL

Eligible participant with at least moderate intensity of pain (an average daily pain score of ≥ 4 on the 11 point PI-NRS at baseline) will receive 7.5 mg twice daily (bid) GW856553 for 28 days.

Drug: GW856553

Interventions

GW856553 DRUG

GW856553 is a film coated white tablet, 9mm round, biconvex, plain faced. It will be administered 7.5mg bid, orally with food at breakfast and dinner.

Active

PLACEBO DRUG

Matching Placebo is a film coated white tablet, 9mm round, biconvex, plain faced. It will be administered orally with food at breakfast and dinner.

PLACEBO

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18 - 80 years inclusive, at the time of signing the informed consent.
• Female of non-child bearing potential or child bearing potential who agrees to use appropriate contraception methods.
• A diagnosis of peripheral neuropathic pain
• Focal neuropathic pain related to nerve injury caused by trauma or surgery not associated with an acute medical condition or injury by avulsion (examples include but are not limited to neuropathic pain secondary to surgical procedures such as thoracotomy, mastectomy, inguinal herniorrhaphy and radical neck dissection, traumatic mononeuropathies and brachial plexus or lumbosacral injuries due to bullet wounds, lacerations, road traffic accidents etc).
• Location of pain consistent with the area innervated by the affected nerve(s), with or without other sensory symptoms in the affected area.
• Duration of pain should be at least 12 weeks since the initial insult.
• Subjects on medications for neuropathic pain (including tricyclic antidepressants, anticonvulsants, opioids, tramadol, bupropion, venlafaxine, mexiletine, muscle relaxants, N-methyl-D-aspartate (NMDA) antagonists) but excluding but excluding non-steroidal anti-inflammatory drugs (NSAIDs), cycloxygenase-2 inhibitors (COX-2) , topical lidocaine, topical capsaicin, nerve blocks and steroid injections may only be included in the study if they have been on stable doses of such medications for at least 4 weeks prior to baseline period (Day -7).
• Participants who have been on NSAIDs, COX-2 inhibitors and topical lidocaine may only be included in the study if they have stopped these medications for at least 5 half-lives prior to the baseline period (Day -7). In the case of topical capsaicin, subjects should have stopped this for at least 8 weeks prior to the baseline period.
• Participants who have received nerve blocks or steroid injections for neuropathic pain may be included if their most recent treatment was at least 4 weeks prior to the baseline period (Day -7).
• Subjects' baseline average daily pain score on the PI-NRS, calculated as the average of their daily PI-NRS scores over the 7 days prior to Day 1, is greater than or equal to 4 on the PI-NRS, after wash-out of prohibited medications. Subjects will need to have recorded their daily PI-NRS for a minimum of 4 days during the 7 days prior to Day 1. Subjects will not be told prior to the completion of the baseline period that the entry requirement of the average PI-NRS is at least 4, in order not to bias their pain intensity score during the baseline period.
• Male subjects must agree to use appropriate contraception methods.
• Body weight \>=50 kg for men and \>=45 kg for women.
• Participants has provided full written informed consent prior to the performance of any protocol-specified procedure, which includes compliance with the requirements and restrictions.
• Single QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) \< 450 msec; or QTc \< 480 milliseconds (msec) in subjects with Bundle Branch Block. If the first QTc exceeds the above limits, repeat the ECG twice at least 5 min apart and take the mean of the three QTc values to determine that the mean QTc satisfies the above limits.
• A subject with a clinical abnormality or other laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

You may not qualify if:

• Subjects with other causes for their neuropathic pain \[e.g. trigeminal neuralgia, painful diabetic neuropathy, mononeuritis multiplex, central post-stroke pain, failed back surgery, phantom limb pain, peripheral neuropathy due to alcoholism, malignancy, human immunodeficiency virus (HIV), syphilis, drug abuse, cobalamin (vitamin B12) deficiency, hypothyroidism, liver disease, toxic exposure\], substantial somatic pain component or more than one cause or potential cause for pain symptoms or nerve entrapment or chronic neck or back pain of more than mild degree or any concurrent rheumatic disease such as but not limited to fibromyalgia or rheumatoid arthritis.
• Subjects with intractable pain of unknown origin or active infection/inflammation in the area of nerve injury.
• Subjects who have had extensive soft tissue injury associated with extensive surgery in the treatment of their nerve injury. Any question regarding the definition of extensive surgery should be discussed with the GSK medical monitor.
• A positive pre-study drug/alcohol screen. However, a positive drug screen will not automatically exclude a subject if there is a medical explanation for the positive result other than drug abuse e.g. a subject who is taking opioids for their neuropathic pain.
• A positive test for HIV antibody.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• History of any liver disease within the last 6 months.
• History of excessive regular alcohol consumption within 6 months of the study.
• History or presence of significant cardiovascular, gastro-intestinal, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs which, in the opinion of the Investigator may interfere with the study procedures or compromise subject safety.
• History or presence of any clinically significant abnormality in vital signs / ECG / laboratory tests, or have any medical or psychiatric condition, which, in the opinion of the Investigator, may interfere with the study procedures or compromise subject safety.
• Subject has clinical evidence of recent major depression (by medical history) except those subjects already controlled by anti-depressants at screening.
• Changes to medications permitted for the treatment of neuropathic pain within 4 weeks of the baseline period (Day -7), including dose adjustment, withdrawal of medications or initiation of new medications.
• Subjects who are unable to maintain the same medications for the treatment of neuropathic pain at the same stable dose as at baseline during the study.
• Unable to refrain from excessive use of sedative medications (e.g. benzodiazepines prescribed as hypnotics) that in the opinion of the Investigator may interfere with efficacy or safety assessments.
• Use of other prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication or during the study, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety or introduce a risk of drug-drug interactions.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (23)

GSK Investigational Site

Broadmeadow, New South Wales, 2292, Australia

Location

GSK Investigational Site

St Leonards, New South Wales, 2065, Australia

Location

GSK Investigational Site

Aarhus C, 8000, Denmark

Location

GSK Investigational Site

Koebenhavn NV, Denmark

Location

GSK Investigational Site

Odense C, 5000, Denmark

Location

GSK Investigational Site

Oslo, 0027, Norway

Location

GSK Investigational Site

Oslo, 0514, Norway

Location

GSK Investigational Site

Trondheim, 7030, Norway

Location

GSK Investigational Site

Tønsberg, 3103, Norway

Location

GSK Investigational Site

Irkutsk, 664003, Russia

Location

GSK Investigational Site

Kazan', 420021, Russia

Location

GSK Investigational Site

Moscow, 117292, Russia

Location

GSK Investigational Site

Yaroslavl, 150030, Russia

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Granada, 18014, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Ourense, 32005, Spain

Location

GSK Investigational Site

Gothenburg, SE-413 45, Sweden

Location

GSK Investigational Site

Linköping, SE-581 85, Sweden

Location

GSK Investigational Site

Stockholm, SE-115 22, Sweden

Location

GSK Investigational Site

London, W12 0NN, United Kingdom

Location

Related Publications (1)

• Thor Ostenfeld, Nathalie E. Richard, Alok Krishen, Robert Y. Lai, Jonathan Bullman, Amanda J. Baines, Joanne Green, Praveen Anand, Madeline Kelly . A randomised, double blind, placebo controlled study to evaluate the analgesic efficacy and safety of the novel p38 MAP kinase inhibitor, losmapimod, in patients with neuropathic pain following peripheral nerve injury . Eur J Pain. 2012;(Dec 14):

  BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Neuralgia; Peripheral Nerve Injuries

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Trauma, Nervous System; Wounds and Injuries

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2009
• First Posted: August 31, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: February 17, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share

Locations

RU (4); SE (3); ES (6); GB (1); AU (2); DK (3); NO (4)