This study will be a double-blind, placebo-controlled, parallel group study. After enrolment and initial assessments, subjects will receive oral GW856553 7.5 milligram (mg) twice daily (BID) or matching placebo for 28 days in a 1:1 ratio. Sufficient numbers of subjects will be recruited to obtain 142 evaluable subjects. This is a double-blind, randomized, 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 randomized treatment period of 4 weeks and a follow-up period of approximately 2 weeks. This is a multi-centre, double-blind, randomized, placebo-controlled study in subjects who have at least moderate intensity of neuropathic pain resulting from peripheral nerve injury due to trauma or surgery. It will investigate the efficacy, safety and tolerability of GW856553 over 28 days of treatment. Approximately 158 subjects will be randomized to ensure 142 evaluable subjects. Randomization ratio will be 1:1 for placebo or GW856553 respectively. The dose of GW856553 will be 7.5 mg BID.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
168
GW856553 is a film coated white tablet, 9mm round, biconvex, plain faced. It will be administered 7.5mg bid, orally with food at breakfast and dinner.
Matching Placebo is a film coated white tablet, 9mm round, biconvex, plain faced. It will be administered orally with food at breakfast and dinner.
GSK Investigational Site
Broadmeadow, New South Wales, Australia
GSK Investigational Site
St Leonards, New South Wales, Australia
GSK Investigational Site
Aarhus C, Denmark
GSK Investigational Site
Koebenhavn NV, Denmark
GSK Investigational Site
Odense C, Denmark
GSK Investigational Site
Oslo, Norway
GSK Investigational Site
Oslo, Norway
GSK Investigational Site
Trondheim, Norway
GSK Investigational Site
Tønsberg, Norway
GSK Investigational Site
Irkutsk, Russia
...and 13 more locations
Change in average daily pain score from baseline to Week 4 of treatment based on the 11 point Pain Intensity Numerical Rating Scale (PI-NRS)
The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Participants rated the pain intensity for the neuropathic pain associated with the nerve injury and not pain from other concomitant causes. Change from baseline was calculated as endpoint value minus the baseline value.
Time frame: Baseline (Day -7) and Week 4
Change in average daily pain score from baseline to Weeks 1, 2 and 3 of treatment and the week before the follow-up visit
The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Participants rated the pain intensity for the neuropathic pain associated with the nerve injury and not pain from other concomitant causes. Change from baseline was calculated as endpoint value minus the baseline value.
Time frame: Baseline (Day -7) and up to Week 3
Change from baseline in intensity of Dynamic Allodynia at Days 14 and 28 of treatment
Dynamic allodynia is a ten point scale with 0=no pain and 10=maximum pain. Intensity of dynamic allodynia was evaluated at the location of the participant's area of greatest tenderness related to the peripheral nerve injury. Change from baseline was calculated as endpoint value minus the baseline value.
Time frame: Baseline (Day -7) and Day 14, 28
Change from baseline in intensity of static hyperalgesia at Days 14 and 28 of treatment
The static hyperalgesia is an 10 point scale with 0=no pain and 10=maximum pain. Intensity of static mechanical hyperalgesia was evaluated at the location of the participant's area of greatest tenderness related to the peripheral nerve injury. Change from baseline was calculated as endpoint value minus the baseline value.
Time frame: Baseline (Day -7) and Day 14, 28
Change from baseline in pain quality on the Short-Form McGill Pain Questionnaire (SF-MPQ) at Days 14 and 28 of treatment and the follow-up visit
Each of 11 sensory and 4 affective descriptors were rated by the participant on a 4-point intensity scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) and intensities were summed to provide sensory and affective scores, respectively. All 15 descriptors were used to calculate a total score. Change from baseline was calculated as endpoint value minus the baseline value.
Time frame: Baseline (Day -7) and Day 14, 28
Change from baseline in Galer Neuropathic Pain Scale to Days 14 and 28 of treatment and the follow-up visit
Each of 10 descriptors (2 that assess global dimensions of pain intensity and unpleasantness and 8 that assess specific qualities of neuropathic pain) were rated by the participant on an 11-point scale (0 = "no pain" or "not painful" and 10 = "the most painful sensation imaginable"). The ratings were added to provide a total score. Intent-to-Treat. Here, n= number of participants analyzed at particular time point.
Time frame: Baseline (Day -7), Day 14, 28 and follow-up (within approximately 14 days post Week 4)
Number of participants who have greater than or equal to (>=) 30 percent (%) and >=50% reduction in average daily pain score
Data for participants who had \>= 30 % and \>=50% reduction in average daily pain score have been reported. Data for number of participants has been reported.
Time frame: Week 1, 2, 3, 4 and a week before follow-up (within approximately 14 days post Week 4)
Number of Participants who have improved, much improved or very much improved relative to baseline on the Patient Global Impression of Change (PGIC)
PGIC assessed the change in overall status as perceived participant, respectively, according to a 7-point numerical rating scale (1- no change, 5-minimally worse, 6-much worse and 7, very much worse). Data for number of participants has been reported.very much improved, 2- much improved, 3-minimally improved, 4-
Time frame: Week 2, 4 and follow-up (within approximately 14 days post Week 4)
Number of Participants who have who have improved, much improved or very much improved relative to baseline on the Clinical Global Impression of Change (CGIC)
CGIC assessed the change in overall status as perceived by the clinician, according to a 7-point numerical rating scale (1- Very much improved, 2- much improved, 3- minimally improved, 4- no change, 5- minimally worse, 6- much worse and 7-very much worse).
Time frame: Week 2, Week 4 and follow-up(within approximately 14 days post Week 4)
Change from baseline in the amount of rescue medication used at Week 4 of treatment
Any participant for whom the pain intensity became unacceptable during any stage of the study, including during washout period of prohibited analgesic medications, were permitted to initiate rescue analgesic therapy with paracetamol/acetaminophen up to a maximum dose of two 500 mg tablets two times daily (i.e., 2,000 mg per 24 hour period). Change from baseline is calculated as baseline value minus the endpoint value.
Time frame: Baseline (Day -7) and Week 4
Change from baseline in total Profile of Mood States (POMS) score and POMS domains scores up to Week 2 and 4 of treatment
POMS is a list of 65 descriptors of mood that are each rated on a five point scale by subjects (0=applies not at all, 4=applies extremely) and that yield six scores: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue inertia and confusion-bewilderment, as well as an overall mood disturbance score. Change from baseline is calculated as baseline value minus the endpoint value.
Time frame: Baseline (Day -7), Week 2 and 4
Change from baseline in SF-36 Health to Day 28 of treatment.
The SF-36 is a subject-completed 36-item questionnaire used to evaluate participant's perception of their general quality of life in 8 areas: physical functioning, role physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role emotional (role limitations caused by emotional problems), vitality and general perception of health. Change from baseline is calculated as baseline value minus the endpoint value.
Time frame: Baseline (Day -7) and Week 4
Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time frame: Up to follow-up (within approximately 14 days post Week 4)
Pre-dose and post-dose plasma GW856553 concentrations on Days 14 and 28
Blood samples were withdrawn to analyze Pre-dose and post-dose plasma GW856553 concentrations on Pre-dose (0 hour), 0-1, 1-2.5, 8-10, 10-12, 12-14 and 14-18 hours post-dose on Day 14 and 28.
Time frame: Pre-dose (0 hour), 0-1, 1-2.5, 8-10, 10-12, 12-14 and 14-18 hours post-dose on Day 14 and 28
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.