Clinical trial NCT01110057: Efficacy Study in Lumbosacral Radiculopathy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain, Neuropathic
Keywords: p38 kinase inhibitor
male and female
patients
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-04-23
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be a double-blind, placebo-controlled, parallel group study. After enrolment and initial assessments, subjects will receive 35 days of study medication. During this treatment period, they will be randomised to either oral GW856553 7.5mg BID or matching placebo in a 1:1 ratio. Sufficient numbers of subjects will be recruited to obtain 128 evaluable subjects.

Detailed description: This is a double-blind, randomised, placebo-controlled, parallel group study. Subjects will undertake a screening period which may last up to approximately 3 weeks, followed by a baseline period of 1 week, a randomised treatment period of 5 weeks and a follow-up period of approximately 2 weeks.

This is a multi-centre, double-blind, randomised, placebo-controlled study in subjects who have at least moderate intensity of neuropathic pain resulting from lumbosacral radiculipathy. It will investigate the efficacy, safety and tolerability of GW856553.

Approximately 142 subjects will be randomised to ensure 128 evaluable subjects. Randomisation ratio will be 1:1 for placebo or GW856553 respectively. The dose of GW856553 will be 7.5 mg BID.

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.

Primary outcomes:
measure: Change in average daily neuropathic pain score from Baseline up to Week 5 (Week 4 of double blind treatment) of treatment
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
Secondary outcomes:
measure: Change in average daily pain intensity rating score (PI-NRS) from Baseline (Day -7 to Day -1) to 5 Weeks
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Change in pain quality on the Short-Form McGill Pain Questionnaire (SF-MPQ) from Baseline up to 5 weeks.
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Number of participants with intensities of pain by SF-MPQ method over 5 weeks
timeFrame: From Baseline (Day -7 to Day -1) up to 5 weeks
measure: Change in Galer Neuropathic Pain Scale score from Baseline up to Week 5
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Percentage of participants with more than or equal to (>=) 30% and >=50% reduction in average daily pain score relative to baseline up to 5 weeks
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Percentage of participants who improved, much improved or very much improved relative to Baseline on the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) over 5 weeks
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Change in the score of the Oswestry Disability Index (ODI) from Baseline (Day -7 to Day -1) up to 5 weeks
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Average total daily dose of rescue medication over 5 weeks
timeFrame: Up to 5 weeks
measure: Change in total Profile of Mood States (POMS) score and POMS domains scores from Baseline to Weeks 3 and 5 of treatment
timeFrame: Baseline, Week 3 (Day 21), and Week 5 (Day 35)
measure: Change in Sleep Interference Scale (SIS) from Baseline over 5 weeks
timeFrame: Baseline (Day -7 to Day -1) and up to 5 weeks
measure: Change from Baseline (Day -7 to Day -1) in SF-36 Health over period
timeFrame: Baseline (Day -7 to Day -1) and Week 4
measure: Change in time to complete timed walk (20 m) from Baseline up to 5 weeks
timeFrame: Baseline (Day -7 to Day -1) and Week 4
measure: Change in walking-associated pain during timed walk from Baseline up to 5 weeks
timeFrame: Baseline and Week 4
measure: Number of participants with death, adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 5 weeks
measure: Number of participants with vital signs outside the range of Potential Clinical Importance (PCI)
timeFrame: Up to 5 weeks
measure: Number of participants with abnormal electrocardiogram (ECG) findings over period
timeFrame: Up to 5 weeks
measure: Number of participants with abnormal clinical chemistry, hematology, and urinalysis parameters over period
timeFrame: From Baseline up to 5 weeks
Other outcomes:
Locations:
city: Hoersholm
country: Denmark
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Bois-Guillaume
country: France
facility: GSK Investigational Site
city: Boulogne-Billancourt
country: France
facility: GSK Investigational Site
city: Lyon cedex 03
country: France
facility: GSK Investigational Site
city: Nice cedex 1
country: France
facility: GSK Investigational Site
city: Paris Cedex 4
country: France
facility: GSK Investigational Site
city: Schoenau
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Leipzg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamar
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Trondheim
country: Norway
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: