Study in Neuropathic Pain Patients With Peripheral Nerve Injury

NCT ID: NCT00969059

Last Updated: 2017-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2010-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

PLACEBO

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

GW856553

Intervention Type: 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.

Interventions

GW856553

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.

Intervention Type: DRUG

PLACEBO

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

Intervention Type: DRUG

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 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.

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.
• Subject has clinical evidence of recent major depression (by medical history) except those subjects already controlled by anti-depressants at screening.
• Subjects who, in the clinical judgement of the investigator, may be malingering or be motivated by secondary gain from participation in the study, will be excluded. Examples for consideration of exclusion include subjects who have compensation or social security claims pending in relation to their peripheral nerve injury or who are appealing against refusal of such claims, but subjects whose claims have been settled need not be excluded.
• 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.
• Unable to stop and remain abstain from non-pharmacological treatments for their neuropathic pain during the study.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the baseline period (Day -7) in the current study: 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• History of hypersensitivity to GW856553 or its components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within a 56 day period.
• Pregnant females as determined by positive urine or serum human chorionic gonadotropin (hCG) test at screening or prior to dosing.
• Lactating females.
• Unwillingness or inability to follow the study procedures
• Subject is mentally or legally incapacitated.
• Subjects with conditions requiring immunosuppressive therapy, or otherwise considered immunosuppressed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Broadmeadow, New South Wales, Australia

GSK Investigational Site

St Leonards, New South Wales, Australia

GSK Investigational Site

Aarhus C, , Denmark

GSK Investigational Site

Koebenhavn NV, , Denmark

GSK Investigational Site

Odense C, , Denmark

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Tønsberg, , Norway

GSK Investigational Site

Irkutsk, , Russia

GSK Investigational Site

Kazan', , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Granada, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Ourense, , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Linköping, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

London, , United Kingdom

Countries

Australia; Denmark; Norway; Russia; Spain; Sweden; United Kingdom

References

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):

Reference Type: BACKGROUND

Study Documents

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

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

Other Identifiers

112967

Identifier Type: -

Identifier Source: org_study_id