Study in Neuropathic Pain Patients With Peripheral Nerve Injury (PNI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00969059
First received: August 27, 2009
Last updated: March 22, 2012
Last verified: March 2012
  Purpose

This study will be a double-blind, placebo-controlled, parallel group study. After enrolment and initial assessments, subjects will receive oral GW856553 7.5mg BID or matching placebo for 28 days in a 1:1 ratio. Sufficient numbers of subjects will be recruited to obtain 142 evaluable subjects.


Condition Intervention Phase
Pain, Neuropathic
Neuropathic Pain
Drug: GW856553
Drug: PLACEBO
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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) (0=no pain, 10=maximum pain imaginable). [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in average daily pain score from baseline to Weeks 1, 2 and 3 of treatment and the week before the follow-up visit. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in intensity of dynamic allodynia (rating scale of 0 to 10, with 0=no pain, 10=maximum pain) from baseline to Days 14 and 28 of treatment. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in intensity of static hyperalgesia (rating scale of 0 to 10, with 0=no pain, 10=maximum pain) from baseline to Days 14 and 28 of treatment. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in pain quality on the Short-Form McGill Pain Questionnaire (SF-MPQ) from baseline to Days 14 and 28 of treatment and the follow-up visit. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in Galer Neuropathic Pain Scale from baseline to Days 14 and 28 of treatment and the follow-up visit. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Proportion of patients who have improved, much improved or very much improved relative to baseline on the Patient Global Impression of Change (PGIC) on Days 14 and 28 of treatment and the follow-up visit. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Proportion of patients who have who have improved, much improved or very much improved relative to baseline on the Clinical Global Impression of Change (CGIC) on Days 14 and 28 of treatment and the follow-up visit. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in total Profile of Mood States (POMS) score and POMS domains scores from baseline to Weeks 2 and 4 of treatment. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in Sleep Interference Scale (SIS) from baseline to Weeks 1, 2, 3 and 4 of treatment. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]
  • Change in SF-36 Health from baseline to Day 28 of treatment. [ Time Frame: 4 WEEKS ] [ Designated as safety issue: No ]

Enrollment: 158
Study Start Date: August 2009
Study Completion Date: October 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: PLACEBO
PLACEBO
Drug: PLACEBO
Placebo to match GW856553
Experimental: Active
GW856553
Drug: GW856553
GW856553 7.5mg bid

Detailed Description:

This is a double-blind, randomised, 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 randomised treatment period of 4 weeks and a follow-up period of approximately 2 weeks.

This is a multi-centre, double-blind, randomised, 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 randomised to ensure 142 evaluable subjects. Randomisation ratio will be 1:1 for placebo or GW856553 respectively. The dose of GW856553 will be 7.5 mg BID.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, NMDA antagonists) but excluding NSAIDs, COX-2 inhibitors, 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).

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.

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, HIV, syphilis, drug abuse, 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 (Section 9.1) 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 GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety or introduce a risk of drug-drug interactions.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00969059

Locations
Australia, New South Wales
GSK Investigational Site
St Leonards, New South Wales, Australia, 2065
Denmark
GSK Investigational Site
Aarhus C, Denmark, 8000
GSK Investigational Site
Koebenhavn NV, Denmark
GSK Investigational Site
Odense C, Denmark, 5000
Russian Federation
GSK Investigational Site
Irkutsk, Russian Federation, 664003
GSK Investigational Site
Kazan, Russian Federation, 420021
GSK Investigational Site
Moscow, Russian Federation, 117292
Spain
GSK Investigational Site
Badalona, Spain, 08916
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Granada, Spain, 18014
GSK Investigational Site
Madrid, Spain, 28006
GSK Investigational Site
Ourense, Spain, 32005
Sweden
GSK Investigational Site
Göteborg, Sweden, SE-413 45
GSK Investigational Site
Linköping, Sweden, SE-581 85
GSK Investigational Site
Stockholm, Sweden, SE-115 22
United Kingdom
GSK Investigational Site
London, United Kingdom, W12 0NN
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00969059     History of Changes
Other Study ID Numbers: 112967
Study First Received: August 27, 2009
Last Updated: March 22, 2012
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Human Research Ethics Committee
Norway: The Royal Norwegian Ministry of Health and Care Services
Russian Federation: Federal service on surveillance in healthcare and social development of Russian Federation
Australia: Medicines Australia
Norway: Statens Legemiddelverk
Spain: Bernat Soria
Norway: Norwegian Medicines Agency
Russia: Russian Ministry of Health
Denmark: Lægemiddelstyrelsen
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
peripheral nerve injury
males and females
p38 kinase inhibitor
patients
neuropathic pain

Additional relevant MeSH terms:
Neuralgia
Wounds and Injuries
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on April 17, 2014