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

XenoPort

Status and phase

Completed

Phase 2

Conditions

Neuralgia, Postherpetic

Treatments

Drug: GEn 3600mg/day

Drug: GEn 1200mg/day

Study type

Interventional

Funder types

Industry

Identifiers

NCT00617461

110527

Details and patient eligibility

About

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.

Full description

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).

Enrollment

96 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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