Neuropathic pain from lumbosacral radiculopathy MedDRA version: 12.0 Level: LLT Classification code 10037779 Term: Radiculopathy
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged 18 – 80 years inclusive, at the time of signing the informed consent. 2. 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 amenorrheaview protocol for further information. • Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 view protocol for further information. 3. A diagnosis of neuropathic pain due to lumbosacral radiculopathy with the following characteristics1: • 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) , view protocol for further information. • 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 and to calculate the total score. View protocol for further information. - 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 =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. View protocol for further information. However, all subjects who are considered eligible by the Investigator on clinical grounds but have not had an CT/MRI undertaken to support the diagnosis of LSR prior to Screening or where a previous CT/MRI scan is not available to the Investigator, are required to have an CT/MRI undertaken during the screening/baseline period (Day -28 to Day -1) view protocol for further information. 4. Subjects on medications for neuropathic pain (view protocol) 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). 5. Subjects who have not received NSAIDs, COX-2 inhibitors and/or topical lidocaine for at least 5 half-lives or 2 weeks, whichever is longer prior to the baseline period (Day -7), and for subjects who have not received topical capsaicin for at least 8 weeks prior to the baseline period. 6. Subjects who have not received nerve blocks and/or steroid injections for neuropathic pain for at least 4 weeks prior t
Exclusion criteria
Exclusion criteria: 1. 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 ?). 2. Subjects with lumbar canal stenosis in which the pain in the lower limbs occur solely on walking and not at rest. 3. Subjects with causes for their neuropathic pain other than that specified in Inclusion Criterion 3 view protocol, 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. 4. 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. 5. A positive test for HIV antibody or positive history of HIV. 6. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening 7. History of any liver disease within the last 6 months [with the exception of known Gilbert’s disease]. 8. History of excessive regular alcohol consumption within 6 months of the study defined as outlined in protocol. 9. 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. 10. 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. 11. Subject has clinical evidence of recent major depression (by medical history) except those subjects already controlled by anti-depressants at screening. 12. 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. View protocol for further information. 13. 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. 14. 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. 15. 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. 16. Use of other prescription or non-prescription drugs, 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 (Day 1) or during the study, view protocol for further information. 17. Unable to stop and remain
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects of repeat oral dosing of GW856553 on neuropathic pain in subjects with lumbosacral radiculopathy.;Secondary Objective: 1. To investigate the effects of repeat oral dosing of GW856553 on low back pain in subjects with lumbosacral radiculopathy. 2. To investigate the effects of repeat oral dosing of GW856553 on sleep, daily function and mood in subjects with pain from lumbosacral radiculopathy. 3. To investigate the safety and tolerability of GW856553 in subjects with lumbosacral radiculopathy. 4. To assess the pharmacokinetics of GW856553 (for patient compliance purposes only).;Primary end point(s): Change in average daily neuropathic pain score from baseline to Week 5 of treatment based on the 11 point Pain Intensity Numerical Rating Scale (PI-NRS) (0=no pain, 10=maximum pain imaginable). | — |
Countries
Denmark, France, Sweden
Outcome results
None listed