Clinical trial NCT00390845 (phase 2, status: completed)
Conditions: pain, neuropathic
ICD codes: E85.1, E85.0, N31.0, N31.1, N31.2, E10.610, E11.610
Drugs: sb681323, placebo
SMILES: CC1=CC(F)=CC=C1C1=C2C=CC(=O)N(C2=NC(NC(CO)CO)=N1)C1=C(F)C=CC=C1F, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility 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.

        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.