Neuropathic pain MedDRA version: 9.1 Level: LLT Classification code 10054095 Term: Neuropathic pain
Conditions
Interventions
Product Code: GSK1838262
Pharmaceutical Form: Tablet
Current Sponsor code: GSK1838262
Other descriptive name: XP13512
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Outpatient subjects aged 18 years or older, with a documented medical diagnosis of PHN of =3 months in duration prior to screening (i.e. pain present for at least 3 months from the healing of a herpes zoster skin rash). 2. A female subject is eligible to enter and participate in the study if she: • Is of non-childbearing potential (refer to Section 11.3). or • Is of child-bearing potential (refer to Section 11.3), is not lactating and has a negative pregnancy test =7 days prior to study treatment initiation and agrees to use one of the GSK specified highly effective methods for avoiding pregnancy (refer to Section 11.4). 3. For the purposes of this study, PHN is defined as pain persisting for =3 months after healing of the shingles rash. Subjects with the above definition of PHN must satisfy the following criteria to be eligible for the study: • Subjects currently on a stable dose of 1800 mg/day of gabapentin1 for 2 weeks or more since the diagnosis of PHN, with inadequate response2; • Subjects not currently treated with gabapentin but previously treated with =1800 mg/day of gabapentin for 4 weeks or more since the diagnosis of PHN with inadequate response2. 1 May previously have been on >1800 mg/day of gabapentin since diagnosis of PHN. 2 Inadequate response will be based on investigator judgement - i.e., some reduction in pain intensity observed but not clinically meaningful for the patient. In either of the above scenarios subjects may have also been previously treated with pregabalin monotherapy (at a dose of 150-300 mg/day) for at least 4 weeks since the diagnosis of PHN with inadequate response2. Subjects showing no response3 to previous treatment with either gabapentin (=1800 mg/day) or pregabalin (150-300 mg/day) taken for at least 4 weeks since the diagnosis of PHN are not eligible for the trial. 3 No response will be based on investigator judgement - i.e., no reduction in pain intensity observed. 4. The baseline 24-hour average pain intensity score is =4.0 based on an 11-point PI-NRS. The baseline score is the calculated mean of the daily scores (based on at least 4 assessments) taken during the 7 days prior to randomization. Subjects are to continue to take gabapentin 1800 mg/day provided by GSK during the Baseline Period. 5. Subject is compliant with the gabapentin treatment supplied during the 14-day Baseline Period. Compliant is defined as administering =80% of the total supplied treatment over the 14-day Baseline Period. 6. Subject is able to provide written informed consent prior to participation in the study. The contents and process of obtaining informed consent will be in accordance with all applicable regulatory requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Has other chronic pain conditions not associated with PHN. However, the subject will not be excluded if ALL the following criteria apply: • The pain is located at a different region of the body. • The pain intensity is not greater than the pain intensity of the PHN ; and • The subject can assess PHN pain independently of the other pain condition. 2. Is unable to discontinue: • Prohibited medications, or • Non-drug therapies or procedures (i.e. nerve blocks, trans-cutaneous electrical nerve stimulation [TENS]) for the relief of pain of PHN for the required washout period and throughout the duration of the study (refer to Section 5.6.2). 3. Has any of the following medical conditions, laboratory abnormalities or disorders: • Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x upper limit of normal (ULN) or alkaline phosphatase or bilirubin > 1.5x ULN. • Chronic hepatitis B or C with a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C Core Antigen Antibody (Hep C antibody). If Hepatitis C antibody test is positive, then the validity of the result should be confirmed by a RIBA before excluding the subject. • Impaired renal function defined as either creatinine clearance 160 mmHg and/or sitting diastolic blood pressure [DBP] >90 mmHg. • Current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drug(s). • Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of XP13512, or, in the investigator’s judgement: • Is considered to be clinically significant and could pose a safety concern or, • Could interfere with the accurate assessment of safety or efficacy or, • Could potentially affect a subject’s safety or study outcome. Examples of such medical conditions include: • Skin conditions at the site of the neuropathy. • Active infection at the site of the neuropathy. • Current or chronic history of liver disease (including acute viral hepatitis), or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). 4. Meets criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) for a major depressive episode or for active significant psychiatric disorders within last year, including dementia, general anxiety disorder, psychosis or bipolar disorder. • Subjects with a history of depression that is in remission, with or without antidepressant treatment, may participate, unless a stable antidepressant regimen includes a prohibited medication. • Antidepressant medication may not be changed or discontinued to meet entry criteria and must be stable for at least three months prior to the start of the Baseline Period. 5. Has a history of clinically significant drug or alcohol abuse as defined by DSM-IV-TR or is unable to refrain from substance abuse throughout the study. Benzodiazepines or atypical benzodiazepines prescribed as hypnotic sleep agents are permitted. 6. Is currently
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to investigate the difference between two doses of XP13512 (3600 mg/day vs. 1200 mg/day) on pain intensity.;Secondary Objective: • To investigate the difference between two doses of XP13512 (3600 mg/day vs. 1200 mg/day) on secondary outcomes including pain-related measures, percentage of subjects achieving various levels of pain reduction, physical functioning and global functioning. • To investigate the safety of XP13512. • To estimate the systemic exposure of gabapentin following 1200 mg/day and 3600 mg/day XP13512 in subjects with inadequate response to 1800 mg/day gabapentin.;Primary end point(s): The primary endpoint is the mean 24-hour average pain intensity score for the last week of treatment of each treatment period based on an 11-point PI-NRS. | — |
Countries
Germany
Outcome results
None listed