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

NCT ID: NCT00617461

Last Updated: 2013-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2009-07-31

Brief 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.

Detailed 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).

Conditions

Neuralgia, Postherpetic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

GEn 1200mg/day

gabapentin enacarbil 1200mg/day, 4 weeks treatment in either the first or second treatment period

Group Type: EXPERIMENTAL

GEn 1200mg/day

Intervention Type: DRUG

1200mg/day gabapentin enacarbil

GEn 3600mg/day

gabapentin enacarbil 3600mg/day, 4 weeks treatment in either the first or second treatment period

Group Type: EXPERIMENTAL

GEn 3600mg/day

Intervention Type: DRUG

3600mg/day gabapentin enacarbil

Interventions

GEn 1200mg/day

1200mg/day gabapentin enacarbil

Intervention Type: DRUG

GEn 3600mg/day

3600mg/day gabapentin enacarbil

Intervention Type: DRUG

Other Intervention Names

GEn; XP13512/GSK1838262; gabapentin enacarbil; gabapentin enacarbil; GEn; XP13512/GSK1838262

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

XenoPort, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Greensburg, Pennsylvania, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Oxnard, California, United States

GSK Investigational Site

Roseville, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

Bradenton, Florida, United States

GSK Investigational Site

Chipley, Florida, United States

GSK Investigational Site

Daytona Beach, Florida, United States

GSK Investigational Site

Fort Myers, Florida, United States

GSK Investigational Site

Gainesville, Florida, United States

GSK Investigational Site

Marianna, Florida, United States

GSK Investigational Site

Miami Springs, Florida, United States

GSK Investigational Site

Naranja, Florida, United States

GSK Investigational Site

South Miami, Florida, United States

GSK Investigational Site

Tallahassee, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Decatur, Georgia, United States

GSK Investigational Site

Marietta, Georgia, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Terre Haute, Indiana, United States

GSK Investigational Site

Kansas City, Missouri, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Missoula, Montana, United States

GSK Investigational Site

Lebanon, New Hampshire, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Greensboro, North Carolina, United States

GSK Investigational Site

Salisbury, North Carolina, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

GSK Investigational Site

Norman, Oklahoma, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Medford, Oregon, United States

GSK Investigational Site

Kingsport, Tennessee, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Longview, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Weber City, Virginia, United States

GSK Investigational Site

Tacoma, Washington, United States

GSK Investigational Site

Yakima, Washington, United States

GSK Investigational Site

Schönau, Baden-Wurttemberg, Germany

GSK Investigational Site

Hüttenberg, Hesse, Germany

GSK Investigational Site

Wiesbaden, Hesse, Germany

GSK Investigational Site

Achim, Lower Saxony, Germany

GSK Investigational Site

Bochum, North Rhine-Westphalia, Germany

GSK Investigational Site

Hattingen, North Rhine-Westphalia, Germany

GSK Investigational Site

Mainz, Rhineland-Palatinate, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzg, Saxony, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

Countries

United States; Germany

References

Harden RN, Freeman R, Rainka M, Zhang L, Bell C, Berges A, Chen C, Graff O, Harding K, Hunter S, Kavanagh S, Schwartzbach C, Warren S, McClung C. A phase 2a, randomized, crossover trial of gabapentin enacarbil for the treatment of postherpetic neuralgia in gabapentin inadequate responders. Pain Med. 2013 Dec;14(12):1918-32. doi: 10.1111/pme.12227. Epub 2013 Sep 18.

Reference Type: DERIVED

PMID: 24102928 (View on PubMed)

Other Identifiers

110527

Identifier Type: -

Identifier Source: org_study_id