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
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
This will be a double-blind, placebo controlled cross-over study. After enrolment and initial assessments, subjects will receive oral SB681323 or matching placebo for 14 days. SB681323 will be administered twice daily at a total daily dose of 7.5mg. Sufficient numbers of patients will be recruited to obtain 40 evaluable patients
Inclusion criteria:
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:
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:
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.
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:
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.