Clinical trial NCT00617461: A Clinical Study in Subjects With Neuropathic Pain From PHN Who Have Had an Inadequate Response to Gabapentin Treatment
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuralgia, Postherpetic
Keywords: Post-herpetic neuralgia(PHN)
Neuropathic pain
Lead sponsor: XenoPort, Inc.
Sponsor class: INDUSTRY
First posted: 2008-02-18
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using Last Observation Carried Forward (LOCF) Data
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data for Each Treatment Period
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
Secondary outcomes:
measure: Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Day-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Current (Evening) Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Night-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Current Morning Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data by Period
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at the Last Week of Each Treatment Period
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at the Last Week of Each Treatment Period Presented by Period Using LOCF Data
timeFrame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Number of Participants Who Are Responders on the Clinical Global Impression of Change (CGIC) Questionnaire at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Number of Participants Who Are Responders on the Clinical Global Impression of Change (CGIC) Questionnaire at the Last Week of Each Treatment Period Presented by Period Using LOCF Data
timeFrame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Mean Sleep Interference Score at the Last Week of Each Treatment Period Using LOCF Data
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period)
measure: Change From Baseline in the Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at the Last Week of Each Treatment Period Using LOCF
timeFrame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of treatment)
measure: Mean Gabapentin Steady-State (ss) Average, Minimum and Maximum Concentrations
timeFrame: A total of 10 blood samples (2 samples at each visit) were collected per participant at Baseline, and the Week 1 and Week 4 visits for each period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Oxnard
country: United States
facility: GSK Investigational Site
state: California
city: Roseville
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Bradenton
country: United States
facility: GSK Investigational Site
state: Florida
city: Chipley
country: United States
facility: GSK Investigational Site
state: Florida
city: Daytona Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Gainesville
country: United States
facility: GSK Investigational Site
state: Florida
city: Marianna
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami Springs
country: United States
facility: GSK Investigational Site
state: Florida
city: Naranja
country: United States
facility: GSK Investigational Site
state: Florida
city: South Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Tallahassee
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Terre Haute
country: United States
facility: GSK Investigational Site
state: Indiana
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Missoula
country: United States
facility: GSK Investigational Site
state: Montana
city: Lebanon
country: United States
facility: GSK Investigational Site
state: New Hampshire
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Norman
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Greensburg
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Longview
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Weber City
country: United States
facility: GSK Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Yakima
country: United States
facility: GSK Investigational Site
state: Washington
city: Schoenau
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Huettenberg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Achim
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Hattingen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.