Study in Neuropathic Pain Patients With Peripheral Nerve Injury

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00969059
• Date of registration: 27/08/2009
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Study in Neuropathic Pain Patients With Peripheral Nerve Injury PNI
• Scientific title: A Randomised, Double Blind Study to Evaluate the Safety and Efficacy of the p38 Kinase Inhibitor, GW856553, in Subjects With Neuropathic Pain From Peripheral Nerve Injury
• Date of first enrolment: August 2009
• Target sample size: 168
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00969059
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Australia, Denmark, Norway, Russian Federation, Spain, Sweden, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female subjects aged 18 - 80 years inclusive, at the time of signing the
informed consent.

- Female of non-child bearing potential or child bearing potential who agrees to use
appropriate contraception methods.

- A diagnosis of peripheral neuropathic pain

- Focal neuropathic pain related to nerve injury caused by trauma or surgery not
associated with an acute medical condition or injury by avulsion (examples include but
are not limited to neuropathic pain secondary to surgical procedures such as
thoracotomy, mastectomy, inguinal herniorrhaphy and radical neck dissection, traumatic
mononeuropathies and brachial plexus or lumbosacral injuries due to bullet wounds,
lacerations, road traffic accidents etc).

- Location of pain consistent with the area innervated by the affected nerve(s), with or
without other sensory symptoms in the affected area.

- Duration of pain should be at least 12 weeks since the initial insult.

- Subjects on medications for neuropathic pain (including tricyclic antidepressants,
anticonvulsants, opioids, tramadol, bupropion, venlafaxine, mexiletine, muscle
relaxants, N-methyl-D-aspartate (NMDA) antagonists) but excluding but excluding
non-steroidal anti-inflammatory drugs (NSAIDs), cycloxygenase-2 inhibitors (COX-2) ,
topical lidocaine, topical capsaicin, nerve blocks and steroid injections 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).

- Participants who have been on NSAIDs, COX-2 inhibitors and topical lidocaine may only
be included in the study if they have stopped these medications for at least 5
half-lives prior to the baseline period (Day -7). In the case of topical capsaicin,
subjects should have stopped this for at least 8 weeks prior to the baseline period.

- Participants who have received nerve blocks or steroid injections for neuropathic pain
may be included if their most recent treatment was at least 4 weeks prior to the
baseline period (Day -7).

- Subjects' baseline average daily pain score on the PI-NRS, calculated as the average
of their daily PI-NRS scores over the 7 days prior to Day 1, is greater than or equal
to 4 on the PI-NRS, after wash-out of prohibited medications. Subjects will need to
have recorded their daily PI-NRS for a minimum of 4 days during the 7 days prior to
Day 1. Subjects will not be told prior to the completion of the baseline period that
the entry requirement of the average PI-NRS is at least 4, in order not to bias their
pain intensity score during the baseline period.

- Male subjects must agree to use appropriate contraception methods.

- Body weight >=50 kg for men and >=45 kg for women.

- Participants has provided full written informed consent prior to the performance of
any protocol-specified procedure, which includes compliance with the requirements and
restrictions.

- Single QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration
corrected for heart rate by Fridericia's formula (QTcF) < 450 msec; or QTc < 480
milliseconds (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.

- A subject with a clinical abnormality or other laboratory parameters outside the
reference range for the population being studied may be included only if the
Investigator and the GSK Medical Monitor agree that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures.

Exclusion Criteria:

- Subjects with other causes for their neuropathic pain [e.g. trigeminal neuralgia,
painful diabetic neuropathy, mononeuritis multiplex, central post-stroke pain, failed
back surgery, phantom limb pain, peripheral neuropathy due to alcoholism, malignancy,
human immunodeficiency virus (HIV), syphilis, drug abuse, cobalamin (vitamin B12)
deficiency, hypothyroidism, liver disease, toxic exposure], substantial somatic pain
component or more than one cause or potential cause for pain symptoms or nerve
entrapment or chronic neck or back pain of more than mild degree or any concurrent
rheumatic disease such as but not limited to fibromyalgia or rheumatoid arthritis.

- Subjects with intractable pain of unknown origin or active infection/inflammation in
the area of nerve injury.

- Subjects who have had extensive soft tissue injury associated with extensive surgery
in the treatment of their nerve injury. Any question regarding the definition of
extensive surgery should be discussed with the GSK medical monitor.

- 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.

- A positive test for HIV antibody.

- 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.

- 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.
Examples for consideration of exclusion include subjects who have compensation or
social security claims pending in relation to their peripheral nerve injury or who are
appealing against refusal of such claims, but subjects whose claims have been settled
need not be excluded.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pain, Neuropathic

Intervention(s)

Drug: PLACEBO

Drug: GW856553

Primary Outcome(s)

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) [Time Frame: Baseline (Day -7) and Week 4]

Secondary Outcome(s)

Change from baseline in Galer Neuropathic Pain Scale to Days 14 and 28 of treatment and the follow-up visit [Time Frame: Baseline (Day -7), Day 14, 28 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 [Time Frame: Baseline (Day -7) and Week 4]

Number of participants who have greater than or equal to (>=) 30 percent (%) and >=50% reduction in average daily pain score [Time Frame: Week 1, 2, 3, 4 and a week before follow-up (within approximately 14 days post 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 [Time Frame: Baseline (Day -7), Week 2 and 4]

Number of participants with Adverse events (AEs) and Serious adverse events (SAEs) [Time Frame: Up to 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) [Time Frame: Week 2, 4 and follow-up (within approximately 14 days post Week 4)]

Change from baseline in intensity of Dynamic Allodynia at Days 14 and 28 of treatment [Time Frame: Baseline (Day -7) and Day 14, 28]

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) [Time Frame: Week 2, Week 4 and follow-up(within approximately 14 days post Week 4)]

Change from baseline in intensity of static hyperalgesia at Days 14 and 28 of treatment [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 [Time Frame: Baseline (Day -7) and Day 14, 28]

Change in average daily pain score from baseline to Weeks 1, 2 and 3 of treatment and the week before the follow-up visit [Time Frame: Baseline (Day -7) and up to Week 3]

Pre-dose and post-dose plasma GW856553 concentrations on Days 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]

Change from baseline in SF-36 Health to Day 28 of treatment. [Time Frame: Baseline (Day -7) and Week 4]

Secondary ID(s)

112967

Source(s) of Monetary Support

Please refer to primary and secondary sponsors