Clinical trial NCT00643760: A Study In Patients With Neuropathic Pain From Diabetic Peripheral Neuropathy (DPN)
Official title: Study PXN110448: A Dose-response Study of XP13512, Compared With Concurrent Placebo Control and LYRICA(Pregabalin), in Subjects With Neuropathic Pain Associated Withdiabetic Peripheral Neuropathy (DPN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuropathy, Diabetic
Keywords: Peripheral Diabetic Neuropathy (PDN)
Neuropathic Pain
Lead sponsor: XenoPort, Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-26
Enrollment: 421
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn is effective in the treatment of neuropathic pain associated with diabetic peripheral neuropathy(DPN)

Detailed description: This is a dose-response study of XP13512 compared with concurrent placebo control and LYRICA (pregabalin), in subjects with neuropathic pain associated with DPN. Three doses of XP13512 (1200 mg/day, 2400 mg/day and 3600 mg/day) are being evaluated for the management of neuropathic pain associated with DPN. Approximately 392 subjects from 70 to 80 participating sites in the US will be randomized to receive either XP13512 at the above mentioned doses, placebo or pregabalin (300mg/day).

Eligibility criteria: Inclusion criteria:

* 18 years or older
* Female subjects are eligible to enter if of non-childbearing potential or not lactating, has a negative pregnancy test and agrees to use a specified highly effective method for avoiding pregnancy
* Documented medical diagnosis of Type 1 or 2 diabetes including:
* Stable glycemic control for 3 months defined as \<25% change of routine insulin, \<50% change of routine oral anti-diabetic agent dose and HbA1c \< 8%. (HbA1c of 8 to 11% eligible if attempts to improve diabetic control failed)
* DPN defined by:
* Bilateral reduced or absent reflexes at the ankles, or
* Bilateral impaired vibration, pinprick, fine touch or temperature perception in the distal lower extremities And
* Persistent distal burning or dull pain in the feet, or
* Persistent proximal aching pain in the legs, or
* Paroxysmal electric, shooting, stabbing pain, or
* Dysasthesias, or
* Evoked pain And
* history of pain for at least six months and no greater than five years attributed to DPN (refers to duration of pain)
* Baseline 24-hour average daily pain intensity score \>4.0 as measured on an 11 point pain intensity numerical rating scale
* Provides written informed consent in accordance with all applicable regulatory requirements

Exclusion criteria:

* Other chronic pain conditions not associated with DPN. However, the subject will not be excluded if:
* The pain condition is located at a different region of the body, and
* The pain intensity of this condition is not greater than the pain intensity of the DPN, and
* The subject can assess their DPN independently of other pain condition.
* Other causes of neuropathy or lower extremity 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 either 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 drug(s)
* Medical condition or disorder that would interfere with the action, absorption, distribution, metabolism, or excretion of GEn or pregabalin, or, in the investigator's judgment:
* Is considered to be clinically significant and could 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
* 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 met entry criteria and must be stable for at least 3 months prior to enrollment
* History of clinically significant drug or alcohol abuse (DSM-IV-TR). 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 DPN, or
* Within six months for studies related to DPN
* Treated previously with GEn
* History of allergic or medically significant adverse reaction to investigational products (including gabapentin or pregabalin) or their excipients, acetaminophen or related compounds

Primary outcomes:
measure: Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at End of Maintenance Treatment (EOMT) Using Last Observation Carried Forward (LOCF) Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Secondary outcomes:
measure: Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Current (Morning) Pain Intensity Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Current (Evening) Pain Intensity Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in the Mean Daily Dose of Rescue Medication at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in Pain Score After Taking a 50-foot Walk at EOMT
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data
timeFrame: EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data
timeFrame: EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score
timeFrame: Any time post-baseline until date of last dose of study medication (up to Week 13)
measure: Change From Baseline in Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at EOMT Using LOCF Data
timeFrame: Baseline and EOMT
measure: Change From Baseline in Quality of Life as Assessed by the 36-Item Short Form Health Survey (SF-36) at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
measure: Change From Baseline in Emotional Functioning as Assessed by the Profile of Mood States-Brief Form (POMS-B) at EOMT Using LOCF Data
timeFrame: Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: GSK Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Dothan
country: United States
facility: GSK Investigational Site
state: Alabama
city: Hoover
country: United States
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state: Alabama
city: Jasper
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city: Muscle Shoals
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facility: GSK Investigational Site
state: Alabama
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facility: GSK Investigational Site
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city: Tuscaloosa
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facility: GSK Investigational Site
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facility: GSK Investigational Site
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city: Peoria
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facility: GSK Investigational Site
state: Arizona
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facility: GSK Investigational Site
state: Arizona
city: Hot Springs
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facility: GSK Investigational Site
state: Arkansas
city: Little Rock
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facility: GSK Investigational Site
state: Arkansas
city: Anaheim
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facility: GSK Investigational Site
state: California
city: Concord
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facility: GSK Investigational Site
state: California
city: Escondido
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facility: GSK Investigational Site
state: California
city: Fresno
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facility: GSK Investigational Site
state: California
city: Huntington Park
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state: California
city: La Jolla
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state: California
city: Los Gatos
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state: California
city: Mission Viejo
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city: Newport Beach
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state: California
city: Northridge
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state: California
city: Oxnard
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facility: GSK Investigational Site
state: California
city: Riverside
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facility: GSK Investigational Site
state: California
city: San Diego
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state: California
city: Santa Ana
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state: California
city: Santa Monica
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state: California
city: Temecula
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city: Walnut Creek
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state: California
city: Westlake Village
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state: California
city: Brandon
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state: Florida
city: Clearwater
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state: Florida
city: Fort Lauderdale
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state: Florida
city: Fort Myers
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state: Florida
city: Hallandale Beach
country: United States
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state: Florida
city: Hollywood
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state: Florida
city: New Port Richey
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city: Pembroke Pines
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state: Florida
city: St. Petersburg
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city: Tallahassee
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state: Florida
city: Atlanta
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state: Georgia
city: Decatur
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city: Marietta
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city: Roswell
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city: Chicago
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city: Libertyville
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city: Evansville
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state: Indiana
city: Evansville
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city: Wichita
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state: Kansas
city: Rockville
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facility: GSK Investigational Site
state: Maryland
city: Wellesley Hills
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Kalamazoo
country: United States
facility: GSK Investigational Site
state: Michigan
city: Olive Branch
country: United States
facility: GSK Investigational Site
state: Mississippi
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: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Flushing
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: North Massapequa
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Staten Island
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Toledo
country: United States
facility: GSK Investigational Site
state: Ohio
city: Norman
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Eugene
country: United States
facility: GSK Investigational Site
state: Oregon
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Levittown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Greer
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Alexandria
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Weber City
country: United States
facility: GSK Investigational Site
state: Virginia
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Vancouver
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rauck R, Makumi CW, Schwartz S, Graff O, Meno-Tetang G, Bell CF, Kavanagh ST, McClung CL. A randomized, controlled trial of gabapentin enacarbil in subjects with neuropathic pain associated with diabetic peripheral neuropathy. Pain Pract. 2013 Jul;13(6):485-96. doi: 10.1111/papr.12014. Epub 2012 Nov 27.