E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuropathic pain from lumbosacral radiculopathy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037779 |
E.1.2 | Term | Radiculopathy |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effects of repeat oral dosing of GW856553 on neuropathic pain in subjects with lumbosacral radiculopathy. |
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E.2.2 | Secondary objectives of the trial |
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). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 to the baseline period (Day -7). 7. 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 view protocol. 8. Male subjects must agree to use the contraception methods listed in Section 8.1. 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. 9. Body weight ≥ 50 kg for men and ≥ 45 kg for women. 10. 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. 11. Single QTcB or QTcF < 450 msec; or QTc < 480 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. 12. A subject with a clinical abnormality or other laboratory parameters outside the reference range for the population being studied may be included view protocol for further information. |
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E.4 | Principal 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 abstained from non-pharmacological treatments for their neuropathic pain during the study as specified in Section 9.3. 18. 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). 19. Exposure to more than four new chemical entities within 12 months prior to the first dosing day (Day 1). 20. 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 GSK Medical Monitor, contraindicates their participation. 21. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 22. Pregnant females as determined by positive urine or serum hCG test at screening or prior to dosing. 23. Lactating females. 24. Unwillingness or inability to follow the procedures outlined in the protocol. 25. Subject is mentally or legally incapacitated. 26. Subjects with conditions requiring immunosuppressive therapy, or otherwise considered immunosuppressed. |
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E.5 End points |
E.5.1 | 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). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |