a clinical study in subjects with neuropathic pain from phn who have had an inadequate response to gabapentin treatment

Conditions: Neuralgia, Postherpetic

Summary: the purpose of this study is evaluate the difference between two doses of gabapentin enacarbil (xp13512/gsk1838262), hereafter referred to as gen, on pain associated with post-herpetic neuralgia.

the primary purpose of study pxn110527 was to investigate the efficacy of a high (3600mg/day) dose versus a low (1200mg/day) dose of gen in subjects with post-herpetic neuralgia (phn) who have a history of an inadequate response to gabapentin treatment. the study is a cross-over design. prior to screening subjects are required to have a demonstrated history of an inadequate response (as determined by the investigator) to at least 1800 mg/day of gabapentin. prior history of treatment with gabapentin includes current treatment at 1800mg/day (2 weeks) or prior treatment with ≥1800mg/day (4 weeks). subjects could also have been treated with pregabalin monotherapy (150-300mg/day, ≥4 weeks) and had an inadequate response. subjects are treated with gabapentin 1800mg/day during the baseline period and are randomized if during the basleline period they are compliant with gabapentin treatment and have a 24-hour average pain intensity score ≥4.0 based on an 11-point pain intensity numerical rating scale (pi-nrs). subjects are then randomized to receive gabapentin enacarbil (either 1200mg/day or 3600mg/day in a 1:1 ratio) for treatment period 1 (28 days). followed by a dose of 2400mg/day for 4 days and the alternate fixed dose (either 3600 mg/day or 1200 mg/day) for treatment period 2 (28 days).

Eligibility criteria:
inclusion criteria: * 18 years or older * documented medical diagnosis of phn with pain present for at least 3 months from the healing of a herpes zoster rash * female subjects are eligible if of non-childbearing potential or not lactating, has a negative pregnancy, and agrees to use one a specified highly effective method for avoiding pregnancy. * currently on a stable dose of 1800 mg/day of gabapentin for ≥2 weeks with inadequate response or * not currently treated with gabapentin, but previously treated with ≥1800 mg/day of gabapentin for 4 weeks or more with inadequate response. * baseline 24-hour average pain intensity score ≥ 4.0 based on an 11-point pi-nrs * provides written informed consent in accordance with all applicable regulatory requirements exclusion criteria: * other chronic pain conditions not associated with phn. however, the subject will not be excluded if: * the pain is located at a different region of the body; and * the pain intensity is not greater than the pain intensity of the phn; and * the subject can assess phn pain independently of other pain * is unable to discontinue prohibited medications or non-drug therapies or procedures throughout the duration of the study * hepatic impairment defined as alt or ast \> 2x upper limit of normal (uln), or alkaline phosphatase or bilirubin \> 1.5x uln * chronic hepatitis b or c * impaired renal function defined as creatinine clearance \<60 ml/min or requiring hemodialysis * corrected qt (qtc) interval ≥ 450 msec or qtc interval ≥480 msec for patients with bundle branch block * uncontrolled hypertension at screen (sitting systolic \>160 mmhg and/or sitting diastolic \>90 mmhg) * current diagnosis of active epilepsy or any active seizure disorder requiring chronic therapy with antiepileptic drugs * medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of gen, or, in the investigator's judgment * is considered to be clinically significant and may 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 * 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). * meets criteria defined by the dsm-iv-tr for a major depressive episode or for active significant psychiatric disorders within last year * depression in remission, with or without antidepressant treatment, may participate, unless stable antidepressant regimen is 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 enrollment * history of clinically significant drug or alcohol abuse (dsm-iv-tr) or is unable to refrain from substance abuse throughout the study. benzodiazepines or atypical benzodiazepines as hypnotic sleep agents permitted. * currently participating in another clinical study in which the subject is, or will be exposed to an investigational or non-investigational drug or device * has participated in a clinical study and was exposed to investigational or non-investigational drug or device: * within preceding month for studies unrelated to phn, or * within preceding six months for studies related to phn * treated previously with gen * history of allergic or medically significant adverse reaction to investigational products (including gabapentin) or their excipients, acetaminophen or related compounds

Keywords: post-herpetic neuralgia(phn) neuropathic pain