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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00390845




Registration number
NCT00390845
Ethics application status
Date submitted
18/10/2006
Date registered
20/10/2006
Date last updated
22/08/2017

Titles & IDs
Public title
P38 Mitogen-activated Protein (Map) Kinase Inhibitor (SB-681323)Study In Patients With Neuropathic Pain
Scientific title
A Double-blind Placebo-controlled Study of the Efficacy and Safety of the P38 Map Kinase Inhibitor SB681323 in Patients With Neuropathic Pain Following Nerve Trauma
Secondary ID [1] 0 0
MKN106762
Universal Trial Number (UTN)
Trial acronym
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SB681323

Experimental: SB681323 - Patients with pain associated with peripheral nerve injury and/or compression will be recruited for this study.

Experimental: Placebo - Patients with pain associated with peripheral nerve injury and/or compression will be recruited for this study.


Treatment: Drugs: SB681323
15 milligrams (mg)/day

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean average Daily Pain Intensity Numeric Rating Scale (PI-NRS) score over period
Timepoint [1] 0 0
Day 1 to 14 of each treatment period
Secondary outcome [1] 0 0
Mean Current pain intensity (CPI) score using PI-NRS over period
Timepoint [1] 0 0
Up to Day 14 of each treatment period
Secondary outcome [2] 0 0
Mean Quantitative Sensory Testing (QST) in cold pain, heat pain and warmth detection threshold on Day 14
Timepoint [2] 0 0
Day 14 of each treatment period
Secondary outcome [3] 0 0
Mean area of static touch allodynia
Timepoint [3] 0 0
Day 1 of each treatment period
Secondary outcome [4] 0 0
Mean area of dynamic touch allodynia
Timepoint [4] 0 0
Day 1 of each treatment period
Secondary outcome [5] 0 0
Mean intensity of static and dynamic touch allodynia
Timepoint [5] 0 0
Day 1 of each treatment period
Secondary outcome [6] 0 0
Number of participants with Global Impression of Change Scale scores over period
Timepoint [6] 0 0
Up to Day 14 of each treatment period
Secondary outcome [7] 0 0
Number of participants who used rescue medication over period
Timepoint [7] 0 0
Day 1 to 14 of each treatment period
Secondary outcome [8] 0 0
Latency of contact heat-evoked potential stimulator (CHEPS) in the affected and control area
Timepoint [8] 0 0
Day 1 of each treatment period
Secondary outcome [9] 0 0
Amplitude of CHEPS in the affected and control area
Timepoint [9] 0 0
Day 1 of each treatment period
Secondary outcome [10] 0 0
Number of participants with skin biopsy results
Timepoint [10] 0 0
80 Days
Secondary outcome [11] 0 0
Number of participants with any adverse event (AE), serious adverse event (SAE) or death
Timepoint [11] 0 0
Up to Follow-up (80 Days)
Secondary outcome [12] 0 0
Number of participants with clinical chemistry values of potential clinical concern (PCC) during treatment period
Timepoint [12] 0 0
Day 1 to Day 14 of each treatment period
Secondary outcome [13] 0 0
Number of participants with hematology values of PCC during treatment period
Timepoint [13] 0 0
Day 1 to Day 14 of each treatment period
Secondary outcome [14] 0 0
Number of participants with vital sign values of PCC during treatment period
Timepoint [14] 0 0
Day 1 to Day 14 of each treatment period
Secondary outcome [15] 0 0
Number of participants with normal and abnormal (not clinically significant [NCS] and clinically significant [CS]) electrocardiogram (ECG) findings
Timepoint [15] 0 0
Day 1 to Day 14 of each treatment period
Secondary outcome [16] 0 0
Number of pregnancies in females of child bearing potential during treatment period
Timepoint [16] 0 0
Up to Follow-up (80 days)

Eligibility
Key inclusion criteria
Inclusion criteria:

* A subject will be eligible for inclusion in this study only if all of the following criteria apply:

Male or female subjects 18-80 years of age

* To be eligible, females patients must have a negative pregnancy test (i.e. serum beta hCG test) and be of:

1. non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status will be confirmed by serum FSH and oestradiol concentrations at screening. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation.

OR b.childbearing potential and agree to commit to one of the protocol-approved methods of contraception, when used consistently and in accordance with both the product label and the instructions of a physician, as indicated below: i.oral contraceptive (combined or progestin only), and the same oral contraceptive regimen has been used for at least two months prior to study drug administration, and the same method continues throughout the study and through the follow-up phase of the study.

ii.progesterone implanted rods (Norplant ) inserted for at least two months prior to the study drug administration (but not beyond the third successive year following insertion) , and is continued throughout the study and through the follow-up phase of the study.

iii.an IUD, inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion) Acceptable IUDs: TCu-380A (Paragard), TCU-380 Slimline (Gyne T Slimline), TCu-220C, MULTILOAD-250 (MLCu-250) and 375, NOVA T and CUNOVAT (Novagard), Levonorgesterol (LNG-20) Intra-uterine System (Mirena/Levonova), and FlexiGard 330/CuFix PP330 (Gynefix). The device must be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and through the follow-up phase of the study.

iv.injectable medroxyprogesterone acetate (e.g., Depo-Provera) and is on a stable dose for 2 months prior to Screen, throughout the study and through the follow-up phase of the study.

v.complete abstinence from intercourse from at least two weeks prior to Screen, throughout the treatment phase, and the follow-up phase.

vi.double barrier method if comprised of a spermicide with either a condom or diaphragm from at least two weeks prior to Screen, throughout the treatment phase, and the follow-up phase.

* A diagnosis of peripheral neuropathic pain:

* focal neuropathic pain related to nerve injury caused by trauma or surgery not associated with ongoing infection (examples include post-thoracotomy syndrome, post-mastectomy syndrome, post-inguinal herniorrhaphy syndrome, post-radical neck dissection syndrome, traumatic mononeuropathies- bullet wounds, lacerations, road traffic accidents)
* pain associated with lumbo-sacral radiculopathy; patients with radiculopathy will only be included if they have pain radiating below the knee and have loss of small fibre function as indicated by quantitative sensory testing (elevation of at least one sensory modality threshold in the symptomatic limb - warm sensation > 9.6 0C and cool sensation > 5.6 0C - in L4, L5 or S1 dermatomes) [Quraishi, 2004].
* carpal tunnel syndrome (CTS); patients with CTS will only be included if there is evidence of loss of large and small fibre function (confirmed by an electrophysiological nerve conduction examination and by quantitative sensory testing - warm sensation > 5.2 0C and cool sensation > 4.5 0C - in median nerve territory (Anand et al., unpublished data).
* location of pain consistent with the area innervated by the affected nerve(s), with or without other sensory symptoms in the affected area
* at least three months duration
* Baseline pain intensity score averaging = 4 during the three day prior to study start as reported on the 11 point pain intensity numerical rating scale. For CTS patients, peak daily pain will be =4 for at least 3 days prior to enrolment
* Subjects who have received nerve blocks or steroid injections for neuropathic pain may be included if their most recent nerve block was at least 4 weeks prior to randomisation.
* Body weight = 50 kg (110 lbs) for men and = 45 kg for women, Body Mass Index 18.5-35kg/m2.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within normal limits at screening.
* The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
* Signed and dated written informed consent prior to admission to the study.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* A subject will not be eligible for inclusion in this study if any of the following criteria apply:
* Any clinically significant medical history or abnormality found on physical examination, laboratory assessment or ECG at screening which, in the opinion of the investigator, could interfere with the interpretation of efficacy or safety data or which otherwise would contraindicate participation in a clinical study, in particular:

* subjects with non-neuropathic pain component involvement, mononeuropathy multiplex, or more than one cause or potential cause for pain symptoms (e.g. trigeminal neuralgia, painful diabetic neuropathy, central post-stroke pain, phantom limb pain, peripheral neuropathy due to alcoholism, malignancy, HIV, syphilis, drug abuse, vitamin deficiency, hypothyroidism, liver disease, toxic exposure, or chronic neck pain);
* subjects with intractable pain of unknown origin or active infection in the area of nerve injury/compression;
* subjects who have had extensive surgery in the treatment of their nerve injury;
* history of Gilbert's syndrome or elevated bilirubin levels (total, direct or indirect) in a previous clinical study or at screening;
* history of increased liver function tests (ALT, AST) above upper limit of normal in the past 6 months;
* positive Hepatitis B surface antigen, positive Hepatitis C antibody or Hepatitis C nucleic acid result;
* GI disorders that may interfere with safety assessments, e.g. diarrhoea.
* Recent start or change in dosing regimen (£1 month prior to screen) of any medication which, in the opinion of the Investigator, may interfere with pain assessments or introduce a risk of drug-drug interactions (e.g. glucocorticoids and some anticonvulsants, see Section 9.2, Prohibited Medications for details).
* Unable to refrain from excessive use medications (e.g. sedatives) that in the opinion of Investigator may interfere with efficacy or safety assessments (benzodiazepines prescribed as hypnotic sleep agents allowed). Subject is unable to discontinue topical analgesics prior to randomization and for the duration of the study. In the case of topical capsaicin this will be extended to 4 weeks.
* Subject is unable to refrain from nerve blocks during the study.
* Positive alcohol test or urine drug screen at screening.
* History of regular alcohol consumption exceeding an average weekly intake of > 21 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 14 units (or an average daily intake of greater than 2 units) for females.
* Consumption of grapefruit or grapefruit juice within seven days prior to the first dose of study medication.
* Donation of blood in excess of 500 mL within a 30-day period prior to dosing.
* Participation in a trial with any drug within 3 months before the start of the study or participation in a trial with a new chemical entity within 4 months before the start of the study.
* Pregnant or nursing female subjects.
* Known history of hypersensitivity or intolerance to paracetamol products.
* Inability or unwillingness to follow the instruction of the study protocol.
* Known hypersensitivity to capsaicin (if applicable)
* An unwillingness of male subjects to abstain from sexual intercourse with women; or unwillingness of the male subject to use a condom/spermicide in addition to having their female partner use another form of contraception (as described in inclusion criterion for women) if the woman could become pregnant from the time of the first dose of investigational product until completion of the follow-up procedures.

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?



Intervention assignment
Crossover
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Broadmeadow
Recruitment hospital [2] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Bayern
Country [2] 0 0
Germany
State/province [2] 0 0
Niedersachsen
Country [3] 0 0
Germany
State/province [3] 0 0
Nordrhein-Westfalen
Country [4] 0 0
Russian Federation
State/province [4] 0 0
Moscow
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Cambridgeshire
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Lanarkshire
Country [7] 0 0
United Kingdom
State/province [7] 0 0
West Midlands
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Liverpool
Country [9] 0 0
United Kingdom
State/province [9] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.