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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00969059




Registration number
NCT00969059
Ethics application status
Date submitted
27/08/2009
Date registered
31/08/2009
Date last updated
17/02/2017

Titles & IDs
Public title
Study in Neuropathic Pain Patients With Peripheral Nerve Injury
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
Secondary ID [1] 0 0
112967
Universal Trial Number (UTN)
Trial acronym
PNI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain, Neuropathic 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GW856553
Treatment: Drugs - PLACEBO

Placebo Comparator: PLACEBO - Eligible participant with at least moderate intensity of pain (an average daily pain score of = 4 on the 11 point PI-NRS at baseline) will receive placebo for 28 days.

Experimental: Active - Eligible participant with at least moderate intensity of pain (an average daily pain score of = 4 on the 11 point PI-NRS at baseline) will receive 7.5 mg twice daily (bid) GW856553 for 28 days.


Treatment: Drugs: GW856553
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.

Treatment: Drugs: PLACEBO
Matching Placebo is a film coated white tablet, 9mm round, biconvex, plain faced. It will be administered orally with food at breakfast and dinner.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Baseline (Day -7) and Week 4
Secondary outcome [1] 0 0
Change in average daily pain score from baseline to Weeks 1, 2 and 3 of treatment and the week before the follow-up visit
Timepoint [1] 0 0
Baseline (Day -7) and up to Week 3
Secondary outcome [2] 0 0
Change from baseline in intensity of Dynamic Allodynia at Days 14 and 28 of treatment
Timepoint [2] 0 0
Baseline (Day -7) and Day 14, 28
Secondary outcome [3] 0 0
Change from baseline in intensity of static hyperalgesia at Days 14 and 28 of treatment
Timepoint [3] 0 0
Baseline (Day -7) and Day 14, 28
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline (Day -7) and Day 14, 28
Secondary outcome [5] 0 0
Change from baseline in Galer Neuropathic Pain Scale to Days 14 and 28 of treatment and the follow-up visit
Timepoint [5] 0 0
Baseline (Day -7), Day 14, 28 and follow-up (within approximately 14 days post Week 4)
Secondary outcome [6] 0 0
Number of participants who have greater than or equal to (>=) 30 percent (%) and >=50% reduction in average daily pain score
Timepoint [6] 0 0
Week 1, 2, 3, 4 and a week before follow-up (within approximately 14 days post Week 4)
Secondary outcome [7] 0 0
Number of Participants who have improved, much improved or very much improved relative to baseline on the Patient Global Impression of Change (PGIC)
Timepoint [7] 0 0
Week 2, 4 and follow-up (within approximately 14 days post Week 4)
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
Week 2, Week 4 and follow-up(within approximately 14 days post Week 4)
Secondary outcome [9] 0 0
Change from baseline in the amount of rescue medication used at Week 4 of treatment
Timepoint [9] 0 0
Baseline (Day -7) and Week 4
Secondary outcome [10] 0 0
Change from baseline in total Profile of Mood States (POMS) score and POMS domains scores up to Week 2 and 4 of treatment
Timepoint [10] 0 0
Baseline (Day -7), Week 2 and 4
Secondary outcome [11] 0 0
Change from baseline in SF-36 Health to Day 28 of treatment.
Timepoint [11] 0 0
Baseline (Day -7) and Week 4
Secondary outcome [12] 0 0
Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)
Timepoint [12] 0 0
Up to follow-up (within approximately 14 days post Week 4)
Secondary outcome [13] 0 0
Pre-dose and post-dose plasma GW856553 concentrations on Days 14 and 28
Timepoint [13] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

- Changes to medications permitted for the treatment of neuropathic pain within 4 weeks
of the baseline period (Day -7), including dose adjustment, withdrawal of medications
or initiation of new medications.

- 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.

- 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.

- Use of other prescription or non-prescription drugs, including vitamins, herbal and
dietary supplements (including St John's Wort) 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 or during the study, unless in the opinion of the
Investigator and Medical Monitor the medication will not interfere with the study
procedures or compromise subject safety or introduce a risk of drug-drug interactions.

- Unable to stop and remain abstain from non-pharmacological treatments for their
neuropathic pain during the study.

- 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).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- 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 Medical Monitor,
contraindicates their participation.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 milliliter (mL) within a 56 day period.

- Pregnant females as determined by positive urine or serum human chorionic gonadotropin
(hCG) test at screening or prior to dosing.

- Lactating females.

- Unwillingness or inability to follow the study procedures

- Subject is mentally or legally incapacitated.

- Subjects with conditions requiring immunosuppressive therapy, or otherwise considered
immunosuppressed.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2010
Sample size
Target
Accrual to date
Final
168
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Broadmeadow
Recruitment hospital [2] 0 0
GSK Investigational Site - St Leonards
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
Denmark
State/province [1] 0 0
Aarhus C
Country [2] 0 0
Denmark
State/province [2] 0 0
Koebenhavn NV
Country [3] 0 0
Denmark
State/province [3] 0 0
Odense C
Country [4] 0 0
Norway
State/province [4] 0 0
Oslo
Country [5] 0 0
Norway
State/province [5] 0 0
Trondheim
Country [6] 0 0
Norway
State/province [6] 0 0
Tønsberg
Country [7] 0 0
Russian Federation
State/province [7] 0 0
Irkutsk
Country [8] 0 0
Russian Federation
State/province [8] 0 0
Kazan
Country [9] 0 0
Russian Federation
State/province [9] 0 0
Moscow
Country [10] 0 0
Russian Federation
State/province [10] 0 0
Yaroslavl
Country [11] 0 0
Spain
State/province [11] 0 0
Badalona
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Granada
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
Spain
State/province [15] 0 0
Ourense
Country [16] 0 0
Sweden
State/province [16] 0 0
Göteborg
Country [17] 0 0
Sweden
State/province [17] 0 0
Linköping
Country [18] 0 0
Sweden
State/province [18] 0 0
Stockholm
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00969059
Trial related presentations / publications
Thor Ostenfeld, Nathalie E. Richard, Alok Krishen, Robert Y. Lai, Jonathan Bullman, Amanda J. Baines, Joanne Green, Praveen Anand, Madeline Kelly . A randomised, double blind, placebo controlled study to evaluate the analgesic efficacy and safety of the novel p38 MAP kinase inhibitor, losmapimod, in patients with neuropathic pain following peripheral nerve injury . Eur J Pain. 2012;(Dec 14):
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00969059