Clinical trial NCT01110057 (phase 2, status: completed)
Conditions: pain, neuropathic
ICD codes: E85.1, E85.0, N31.0, N31.1, N31.2, E10.610, E11.610
Drugs: placebo, gs856553
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Key Inclusion Criteria:

          -  Male or female subjects aged 18 - 80 years inclusive, at the time of signing the
             informed consent.

          -  A female subject is eligible to participate if she is of:

        Non-childbearing potential defined as pre-menopausal females with a documented tubal
        ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea
        Child-bearing potential and agrees to use one of the contraception methods listed in the
        protocol for an appropriate period of time (as determined by the product label or
        investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy
        at that point. Female subjects must agree to use contraception until 14 days after the last
        dose of study medication. Male subjects must agree to use the contraception methods listed
        in the protocol

          -  A diagnosis of neuropathic pain due to lumbosacral radiculopathy with the following
             characteristics:

          -  Pain perceived in one or both lower limbs at sites consistent with the area innervated
             by the L4, L5 or S1 nerve roots, with or without other sensory symptoms in the
             affected areas; (typically, the pain may be perceived in the buttock, thigh, calf,
             leg, foot or toes).

          -  History of the pain suggestive that the cause of lumbosacral radiculopathy is due to
             injury of the lumbosacral nerve root(s) by degenerative disease of the vertebrae in
             the lumbosacral spine or associated soft tissues including the intervertebral discs,
             or secondary to spinal injury and not due to infection/abscess, haematoma or
             malignancy.

          -  Duration of pain should be at least 12 weeks since onset.

          -  Intensity of pain should be stable for the 2 weeks prior to Screening, based on
             clinical history.

          -  As part of the neurological examination, the investigator must also conduct the
             procedures specified in the Standardised Evaluation of Pain [Neuropathic Pain] (StEP)
             instrument [Scholz, 2009]2, and to calculate the total score. In the clinical opinion
             of the investigator, the diagnosis of lumbosacral radiculopathy should be supported by
             at least one of the following features at Screening or documented in the medical notes
             in relation to the current symptoms:

        Pain/sensory disturbance in dermatomal/myotomal distribution precipitated or exacerbated by
        straight leg raising (the straight leg raising test should be performed as specified in
        StEP; Neurological examination of lower limbs shows impaired muscle power, sensory function
        or deep tendon reflexes in the territory of the affected nerve roots; The total StEP score
        is greater than 4 (indicative of lumbosacral radiculopathy as the cause of the pain);
        Electromyographic (EMG) evidence of denervation in muscles innervated by the affected nerve
        roots; Quantitative sensory tests (QST) showing evidence of altered sensory thresholds in
        dermatomes innerved by the affected nerve roots;

          -  At Screening, if the investigator is satisfied with the diagnosis based on clinical
             review, or if results from such investigations related to the current symptoms are
             already documented in the medical notes, then it is not essential for the investigator
             to conduct computerised tomography (CT)/magnetic resonance imaging (MRI), EMG or QST.

          -  It is a requirement for all eligible subjects to have the nature of their spinal
             disease established by imaging (CT/MRI) and reviewed by a neuroradiologist /
             Investigator prior to starting study medication. This CT/MRI should be reviewed by the
             Investigator to ensure that it is consistent with the clinical diagnosis without any
             of the aetiologies in the exclusion criteria

          -  Subjects on medications for neuropathic pain (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) and continue with such stable doses during the study.

          -  Subjects' baseline average daily pain score for neuropathic pain due to LSR on the
             PI-NRS, calculated as the average of their daily PI-NRS scores over the baseline
             period (Day -7 to Day -1), is greater than or equal to 4 on the PI-NRS, after wash-out
             of prohibited medications. Male subjects must agree to use the contraception methods
             listed in the protocol. This criterion must be followed from the time of the first
             dose of study medication until 14 days after the last dose of study medication.

          -  Subject has provided full written informed consent prior to the performance of any
             protocol-specified procedure, which includes compliance with the requirements and
             restrictions listed in the consent form.

        Key Exclusion Criteria:

          -  Subjects who, in the opinion of the Investigator, are unable to reliably delineate or
             assess their own pain by anatomical location/distribution (e.g. can the subject
             reliably tell the difference between their back pain and their lower limb pain and
             rate their intensity separately ?).

          -  Subjects with lumbar canal stenosis in which the pain in the lower limbs occur solely
             on walking and not at rest.

          -  Subjects with causes for their neuropathic pain other than that specified in the
             inclusion criteria [e.g. post-herpetic neuralgia, painful diabetic neuropathy,
             mononeuritis multiplex, central post-stroke pain, failed back surgery in relation to
             the presenting episode of radiculopathy, spinal
             abscess/infection/haematoma/malignancy, phantom limb pain, peripheral neuropathy due
             to alcoholism, malignancy, HIV, syphilis, drug abuse, vitamin B12 deficiency,
             hypothyroidism, liver disease, toxic exposure], pain associated with a substantial
             somatic pain component [e.g.non-neuropathic / musculoskeletal pain in lower limbs or
             other parts of the body apart from the back] or more than one cause or potential cause
             for pain symptoms or any concurrent rheumatic disease such as but not limited to
             fibromyalgia, rheumatoid arthritis or significant osteoarthritis. Any question
             regarding the acceptability of aetiology of the neuropathic pain should be discussed
             with the GSK medical monitor.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for HIV antibody or positive history of HIV.

          -  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 [with the exception of known
             Gilbert's disease].

          -  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.

          -  Unable to stop and remain abstained from non-pharmacological treatments for their
             neuropathic pain during the study

          -  History of hypersensitivity to GW856553 or its components thereof or a history of drug
             or other

          -  Pregnant or lactating females

          -  Subjects with conditions requiring immunosuppressive therapy, or otherwise considered
             immunosuppressed.