A randomised, double blind study to evaluate the safety and efficacy of the p38 kinase inhibitor, GW856553, in subjects with neuropathic pain from lumbosacral radiculopathy

Phase 1

• Conditions: europathic pain from lumbosacral radiculopathy; MedDRA version: 12.0Level: LLTClassification code 10037779Term: Radiculopathy

• Registration Number: EUCTR2009-012836-33-FR
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-10-09
• Study Completion: 2010-08-23
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effects of repeat oral dosing of GW856553 on neuropathic pain in<br>subjects with lumbosacral radiculopathy.;Secondary Objective: 1. To investigate the effects of repeat oral dosing of GW856553 on low back pain in<br>subjects with lumbosacral radiculopathy.<br><br>2. To investigate the effects of repeat oral dosing of GW856553 on sleep, daily<br>function and mood in subjects with pain from lumbosacral radiculopathy.<br><br>3. To investigate the safety and tolerability of GW856553 in subjects with lumbosacral<br>radiculopathy.<br><br>4. To assess the pharmacokinetics of GW856553 (for patient compliance purposes<br>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<br>Intensity Numerical Rating Scale (PI-NRS) (0=no pain, 10=maximum pain imaginable).