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

Phase 1

Conditions: europathic pain

Registration Number: EUCTR2006-001072-21-GB

Lead Sponsor: GlaxoSmithKline Research and Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1. Male or female subjects 18-80 years of age
2. To be eligible, females patients must be of:
a. 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 have a negative pregnancy test 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 (e.g. 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), 375 and 375 SL, 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.
3. 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

Exclusion Criteria

1. 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 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;
• 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.
2. Recent start or change in dosing regimen (=1 month prior to randomisation) of any medication which, in the opinion of the Investigator, may interfere with pain
assessments or introduce a risk of drug-drug interactions (see Section 9.2, Prohibited
Medications for details). Subjects may continue to take medications for the treatment
of their neuropathic pain as long as the regimen is stable and does not contain
prohibited medications.
3. 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 (see Section 9.2, Prohibited Medications for details).
4. Subject is unable to refrain from nerve blocks during the study.
5. Positive alcohol test or urine drug screen at screening. 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.
6. 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effect of SB681323 on the clinical signs of neuropathic pain in patients with nerve trauma and/or compression;Primary end point(s): • Average daily pain score based on the 11 point pain intensity numeric rating scale, NRS (0=no pain, 10 maximum pain imaginable) over Week 1 and Week 2 of the treatment;<br> Secondary Objective: •To investigate the effect of SB681323 on experimental psychophysical measures of sensitisation in pain pathways in patients with nerve trauma and/or compression<br> •To investigate the effect of SB681323 on specific measures of the TRPV1 pathway in patients with nerve trauma and/or compression<br> •To investigate the value of these additional exploratory endpoints for future studies in neuropathic pain patients<br> •To assess the safety of SB681323 in patients with neuropathic pain<br>

Secondary Outcome Measures

Name	Time	Method

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