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

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.