A Randomised, Double Blind Study to Evaluate the Safety and Efficacy of the p38 Kinase Inhibitor, GW856553, in Subjects With Neuropathic Pain From Peripheral Nerve Injury

GlaxoSmithKline1 site in 1 country168 target enrollmentAugust 2009

ConditionsPain, Neuropathic

InterventionsPLACEBO GW856553

DrugsGW856553 PLACEBO

Overview

Phase: Phase 2
Intervention: PLACEBO
Conditions: Pain, Neuropathic
Sponsor: GlaxoSmithKline
Enrollment: 168
Locations: 1
Primary Endpoint: 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)
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 2009

End Date

July 2010

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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

Exclusion Criteria

•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.

Arms & Interventions

PLACEBO

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.

Intervention: PLACEBO

Active

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.

Intervention: GW856553

Outcomes

Primary Outcomes

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)

Time Frame: Baseline (Day -7) and Week 4

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.

Secondary Outcomes

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))
Number of participants who have greater than or equal to (>=) 30 percent (%) and >=50% reduction in average daily pain score(Week 1, 2, 3, 4 and a week before follow-up (within approximately 14 days post Week 4))
Number of Participants who have improved, much improved or very much improved relative to baseline on the Patient Global Impression of Change (PGIC)(Week 2, 4 and follow-up (within approximately 14 days post Week 4))
Number of Participants who have who have improved, much improved or very much improved relative to baseline on the Clinical Global Impression of Change (CGIC)(Week 2, Week 4 and follow-up(within approximately 14 days post Week 4))
Change from baseline in the amount of rescue medication used at Week 4 of treatment(Baseline (Day -7) and Week 4)
Change from baseline in SF-36 Health to Day 28 of treatment.(Baseline (Day -7) and Week 4)
Change from baseline in total Profile of Mood States (POMS) score and POMS domains scores up to Week 2 and 4 of treatment(Baseline (Day -7), Week 2 and 4)
Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)(Up to follow-up (within approximately 14 days post Week 4))
Pre-dose and post-dose plasma GW856553 concentrations on Days 14 and 28(Pre-dose (0 hour), 0-1, 1-2.5, 8-10, 10-12, 12-14 and 14-18 hours post-dose on Day 14 and 28)