P38 Mitogen-activated Protein (Map) Kinase Inhibitor (SB-681323)Study In Patients With Neuropathic Pain

NCT00390845 | Completed Phase 2

• 1 other identifier: MKN106762
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 13

Brief Summary

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

Conditions

Pain, Neuropathic

Keywords

MAP kinase; SB681323; neuropathic pain; patients; P38; nerve trauma

Outcome Measures

Primary Outcomes (1)

• Mean average Daily Pain Intensity Numeric Rating Scale (PI-NRS) score over period

  Participants were asked to rate their overall pain intensity for the last 24 hours, daily before retiring to bed. This constituted the Daily Pain Score. The 11 point pain intensity numerical rating scale ranged from 0 to 10, where 0 represents "No pain" and 10 represents "Maximum pain imaginable". It was used for the subjective assessment of the pain. The score ranged from 0 to 10, where 0 represented absence of symptoms and higher score indicated more severe symptoms. The average daily pain over Week 1 (Day 7) was calculated as the mean of days 2 to 6 inclusive and for week 2 (Day 14), days 8 to 13 inclusive. Participants were instructed to record their daily pain score on a dairy card and calculations of average weekly pain scores were performed on the basis of diary cards review.

  Day 1 to 14 of each treatment period

Secondary Outcomes (16)

• Mean Current pain intensity (CPI) score using PI-NRS over period

  Up to Day 14 of each treatment period

• Mean Quantitative Sensory Testing (QST) in cold pain, heat pain and warmth detection threshold on Day 14

  Day 14 of each treatment period

• Mean area of static touch allodynia

  Day 1 of each treatment period

• Mean area of dynamic touch allodynia

  Day 1 of each treatment period

• Mean intensity of static and dynamic touch allodynia

  Day 1 of each treatment period

Study Arms (2)

SB681323

EXPERIMENTAL

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

Drug: SB681323

Placebo

EXPERIMENTAL

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

Drug: Placebo

Interventions

SB681323 DRUG

15 milligrams (mg)/day

SB681323

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Broadmeadow, New South Wales, 2292, Australia

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Würzburg, Bavaria, 97080, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44789, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Moscow, 117292, Russia

Location

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

GSK Investigational Site

Solihull, West Midlands, B91 2JL, United Kingdom

Location

GSK Investigational Site

Liverpool, L9 7LJ, United Kingdom

Location

GSK Investigational Site

London, W12 0NN, United Kingdom

Location

GSK Investigational Site

London, WC1X 8LD, United Kingdom

Location

MeSH Terms

Conditions

Neuralgia

Interventions

dilmapimod

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 20, 2006
• Study Start: August 30, 2006
• Primary Completion: August 11, 2008
• Study Completion: August 11, 2008
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

AU (2); GB (6); DE (4); RU (1)