A Clinical Study in Subjects With Neuropathic Pain From PHN Who Have Had an Inadequate Response to Gabapentin Treatment

Study PXN110527: The Investigation of the Efficacy and Pharmacokinetics of XP13512 in Subjects With Neuropathic Pain Associated With Post-herpetic Neuralgia (PHN) Who Have Had an Inadequate Response to Gabapentin Treatment.

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).

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