A Study In Patients With Neuropathic Pain From Diabetic Peripheral Neuropathy (DPN)
Primary Purpose
Neuropathy, Diabetic
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
GEn 1200mg/day
GEn 2400mg/day
GEn 3600mg/day
Pregabalin
Sponsored by
About this trial
This is an interventional treatment trial for Neuropathy, Diabetic focused on measuring Peripheral Diabetic Neuropathy (PDN), Neuropathic Pain
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
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Other
Experimental
Experimental
Experimental
Arm Label
Placebo
Pregabalin
GEn 1200mg/day
GEn 2400mg/day
GEn 3600mg/day
Arm Description
Placebo
Pregabalin 300mg/day (positive control), maintenance treatment 14 weeks
gabapentin enacarbil 1200mg/day, maintenance treatment 14 weeks
gabapentin enacarbil 2400mg/day, maintenance treatment 14 weeks
gabapentin enacarbil 3600mg/day, maintanance treatment 14 weeks
Outcomes
Primary Outcome Measures
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
Baseline and EOMT values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (Baseline) and the earliest date of Week 13 visit/Withdrawal visit/last dose of study drug (EOMT). Participants used a hand-held diary to rate their API over the preceding 24 hours, using an 11-point Pain Intensity Numerical Rating Scale (PI-NRS) (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. Change from baseline was calculated as the EOMT score minus the Baseline score.
Secondary Outcome Measures
Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
Day-time is defined as the time between rising in the morning and going to bed at night. Participants recorded day-time API on a daily basis in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
Night-time is defined as the time between going to bed at night and rising in the morning. Participants recorded night-time API on a daily basis in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Current (Morning) Pain Intensity Score at EOMT Using LOCF Data
Current pain is defined as the participant's assessment of pain intensity "right now." Participants recorded their current morning pain intensity in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Current (Evening) Pain Intensity Score at EOMT Using LOCF Data
Current pain is defined as the participant's assessment of pain intensity "right now." Participants recorded their current evening pain intensity in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data
Day-time worst pain is defined as the partipant's assessment of their worst pain between rising in the morning and going to bed at night. Participants recorded day-time worst pain in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data
Night-time worst pain is defined as the partipant's assessment of their worst pain between going to bed at night and rising in the morning. Participants recorded night-time worst pain in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data
Participants assessed sleep interference due to pain on a daily basis in the morning upon awakening using an 11-point NRS (0=pain does not interfere with sleep, 10=pain completely interferes with sleep). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in the Mean Daily Dose of Rescue Medication at EOMT Using LOCF Data
Mean daily use of rescue medication (milligrams of acetaminophen) was calculated by determining the average number of tablets taken per day of rescue medication (Commerical Tylenol) during treatment and multiplying that by 500 mg. Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data
The NPS assesses pain qualities and consists of 11-items, 10 assessed on an 11-point NRS (0=no impact to 10=greatest impact); and 1 open-ended question not used in score calculation. 4 summary scores are calculated: NPS 10 (items 1-7, 9-11), NPS 8 (8 pain descriptor items), NPS Non-Allodynic (NA) (8 NA items), and NPS 4 (4 pain quality items); and range from 0 to 100 (0=no impact and 100=greatest impact). The analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data
The SF-MPQ, a general pain instrument, assesses the characteristics and intensity of pain and consists of 15-items assessed on a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe). 3 summary scores are calculated: sensory score (sum of items 1-11, range 0-33), affective score (sum of items 12-15, range 0-12), total score (sum of items 1-15, range 0-45), where lower scores = lower pain/impact. Analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Change From Baseline in Pain Score After Taking a 50-foot Walk at EOMT
Baseline and EOMT scores are the pain scores each participant reported after taking a 50-foot walk at the randomization and Week 13/Withdrawal visits, respectively, using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with BMI, baseline pain intensity after 50-foot walk, pain intensity prior to 50-foot walk at the visit being assessed, and grouped center as covariates was used.
Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data
The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved." EOMT response is defined as the score recorded at the Week 13/Withdrawal visit.
Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data
The CGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the clinician's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved." EOMT response is defined as the score recorded at the Week 13/Withdrawal visit.
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
Baseline and EOMT scores are the calculated means of the 24-hour average pain scores for each participant during the last 7 days prior to randomization and EOMT, respectively. Percent reduction from baseline was calculated as the [(EOMT score minus the baseline score)divided by the baseline score], multiplied by 100. The PI-NRS is an 11-point scale (0=no pain, 10=pain as bad as you can imagine) by which a participant assesses their 24-hour average pain intensity.
Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score
Sustained improvement in the 24-hour average pain intensity score is defined as at least 2 consecutive days on which the 24-hour average pain intensity score is >=2 points less than the mean 24-hour average pain intensity score at baseline. Time to onset is measured from baseline and was calculated as first day of event minus last day of baseline and is expressed in days. Baseline score is the calculated mean of the 24-hour average pain score for each participant during the last 7 days prior to randomization.
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
The BPI, a general pain instrument, assesses the severity and interference of pain; and consists of 6 items assessed on an 11-point NRS (0=no impact and 10=greatest impact). 2 summary scores are calculated: BPI Severity Score (average of first 4 items) and BPI Interference Score (average of 7 responses to item 6); where each summary score ranges from 0 to 10 (0=no impact and 10=greatest impact). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Change From Baseline in Quality of Life as Assessed by the 36-Item Short Form Health Survey (SF-36) at EOMT Using LOCF Data
The SF-36 is a general health-related quality of life instrument consisting of 36 items with various response options (Yes/No, 5- to 6-point Likert scale). Summary scores are calculated for 8 domains and 2 components (physical and mental); where scores range from 0 to 100 (higher scores = better quality of life). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Change From Baseline in Emotional Functioning as Assessed by the Profile of Mood States-Brief Form (POMS-B) at EOMT Using LOCF Data
The POMS-B, an emotional functioning instrument, assesses mood, tension, and other psychological symptoms and consists of 30-items assessed on a 5-point scale (0=not at all to 4=extremely). 6 summary scores are calculated: Tension/Anxiety, Depression/Rejection, Anger/Hostility, Vigor/Activity, Fatigue/Inertia, and Confusion/Bewilderment; and range from 0-20 (higher scores = more negative mood state). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00643760
Brief Title
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
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
XenoPort, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuropathy, Diabetic
Keywords
Peripheral Diabetic Neuropathy (PDN), Neuropathic Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
421 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
Pregabalin
Arm Type
Other
Arm Description
Pregabalin 300mg/day (positive control), maintenance treatment 14 weeks
Arm Title
GEn 1200mg/day
Arm Type
Experimental
Arm Description
gabapentin enacarbil 1200mg/day, maintenance treatment 14 weeks
Arm Title
GEn 2400mg/day
Arm Type
Experimental
Arm Description
gabapentin enacarbil 2400mg/day, maintenance treatment 14 weeks
Arm Title
GEn 3600mg/day
Arm Type
Experimental
Arm Description
gabapentin enacarbil 3600mg/day, maintanance treatment 14 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo
Intervention Type
Drug
Intervention Name(s)
GEn 1200mg/day
Other Intervention Name(s)
XP13512, GSK1838262, gabapentin enacarbil
Intervention Description
gabapentin enacarbil 1200mg/day
Intervention Type
Drug
Intervention Name(s)
GEn 2400mg/day
Other Intervention Name(s)
gabapentin enacarbil, GSK1838262, XP13512
Intervention Description
gabapentin enacarbil 2400mg/day
Intervention Type
Drug
Intervention Name(s)
GEn 3600mg/day
Other Intervention Name(s)
XP13512, GSK1838262, gabapentin enacarbil
Intervention Description
gabapentin enacarbil 3600mg/day
Intervention Type
Drug
Intervention Name(s)
Pregabalin
Intervention Description
pregabalin 300mg/day
Primary Outcome Measure Information:
Title
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
Description
Baseline and EOMT values are the calculated means of the daily 24-hour API scores for each participant during the last 7 days prior to randomization (Baseline) and the earliest date of Week 13 visit/Withdrawal visit/last dose of study drug (EOMT). Participants used a hand-held diary to rate their API over the preceding 24 hours, using an 11-point Pain Intensity Numerical Rating Scale (PI-NRS) (0=no pain, 10=pain as bad as you can imagine). LOCF was used if less than 4 days of diary data were provided. Change from baseline was calculated as the EOMT score minus the Baseline score.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Secondary Outcome Measure Information:
Title
Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
Description
Day-time is defined as the time between rising in the morning and going to bed at night. Participants recorded day-time API on a daily basis in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data
Description
Night-time is defined as the time between going to bed at night and rising in the morning. Participants recorded night-time API on a daily basis in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Current (Morning) Pain Intensity Score at EOMT Using LOCF Data
Description
Current pain is defined as the participant's assessment of pain intensity "right now." Participants recorded their current morning pain intensity in the morning upon wakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Current (Evening) Pain Intensity Score at EOMT Using LOCF Data
Description
Current pain is defined as the participant's assessment of pain intensity "right now." Participants recorded their current evening pain intensity in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data
Description
Day-time worst pain is defined as the partipant's assessment of their worst pain between rising in the morning and going to bed at night. Participants recorded day-time worst pain in the evening before bedtime using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data
Description
Night-time worst pain is defined as the partipant's assessment of their worst pain between going to bed at night and rising in the morning. Participants recorded night-time worst pain in the morning upon awakening using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data
Description
Participants assessed sleep interference due to pain on a daily basis in the morning upon awakening using an 11-point NRS (0=pain does not interfere with sleep, 10=pain completely interferes with sleep). Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in the Mean Daily Dose of Rescue Medication at EOMT Using LOCF Data
Description
Mean daily use of rescue medication (milligrams of acetaminophen) was calculated by determining the average number of tablets taken per day of rescue medication (Commerical Tylenol) during treatment and multiplying that by 500 mg. Baseline and EOMT are as defined for the primary endpoint. Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with baseline value, BMI, grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data
Description
The NPS assesses pain qualities and consists of 11-items, 10 assessed on an 11-point NRS (0=no impact to 10=greatest impact); and 1 open-ended question not used in score calculation. 4 summary scores are calculated: NPS 10 (items 1-7, 9-11), NPS 8 (8 pain descriptor items), NPS Non-Allodynic (NA) (8 NA items), and NPS 4 (4 pain quality items); and range from 0 to 100 (0=no impact and 100=greatest impact). The analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data
Description
The SF-MPQ, a general pain instrument, assesses the characteristics and intensity of pain and consists of 15-items assessed on a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe). 3 summary scores are calculated: sensory score (sum of items 1-11, range 0-33), affective score (sum of items 12-15, range 0-12), total score (sum of items 1-15, range 0-45), where lower scores = lower pain/impact. Analysis is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in Pain Score After Taking a 50-foot Walk at EOMT
Description
Baseline and EOMT scores are the pain scores each participant reported after taking a 50-foot walk at the randomization and Week 13/Withdrawal visits, respectively, using an 11-point PI-NRS (0=no pain, 10=pain as bad as you can imagine). Change from baseline was calculated as the EOMT score minus the baseline score. An ANCOVA model with BMI, baseline pain intensity after 50-foot walk, pain intensity prior to 50-foot walk at the visit being assessed, and grouped center as covariates was used.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data
Description
The PGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved." EOMT response is defined as the score recorded at the Week 13/Withdrawal visit.
Time Frame
EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data
Description
The CGIC is a single-item questionnaire designed to provide an overall assessment of treatment from the clinician's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved." EOMT response is defined as the score recorded at the Week 13/Withdrawal visit.
Time Frame
EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
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
Description
Baseline and EOMT scores are the calculated means of the 24-hour average pain scores for each participant during the last 7 days prior to randomization and EOMT, respectively. Percent reduction from baseline was calculated as the [(EOMT score minus the baseline score)divided by the baseline score], multiplied by 100. The PI-NRS is an 11-point scale (0=no pain, 10=pain as bad as you can imagine) by which a participant assesses their 24-hour average pain intensity.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score
Description
Sustained improvement in the 24-hour average pain intensity score is defined as at least 2 consecutive days on which the 24-hour average pain intensity score is >=2 points less than the mean 24-hour average pain intensity score at baseline. Time to onset is measured from baseline and was calculated as first day of event minus last day of baseline and is expressed in days. Baseline score is the calculated mean of the 24-hour average pain score for each participant during the last 7 days prior to randomization.
Time Frame
Any time post-baseline until date of last dose of study medication (up to Week 13)
Title
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
Description
The BPI, a general pain instrument, assesses the severity and interference of pain; and consists of 6 items assessed on an 11-point NRS (0=no impact and 10=greatest impact). 2 summary scores are calculated: BPI Severity Score (average of first 4 items) and BPI Interference Score (average of 7 responses to item 6); where each summary score ranges from 0 to 10 (0=no impact and 10=greatest impact). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time Frame
Baseline and EOMT
Title
Change From Baseline in Quality of Life as Assessed by the 36-Item Short Form Health Survey (SF-36) at EOMT Using LOCF Data
Description
The SF-36 is a general health-related quality of life instrument consisting of 36 items with various response options (Yes/No, 5- to 6-point Likert scale). Summary scores are calculated for 8 domains and 2 components (physical and mental); where scores range from 0 to 100 (higher scores = better quality of life). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
Title
Change From Baseline in Emotional Functioning as Assessed by the Profile of Mood States-Brief Form (POMS-B) at EOMT Using LOCF Data
Description
The POMS-B, an emotional functioning instrument, assesses mood, tension, and other psychological symptoms and consists of 30-items assessed on a 5-point scale (0=not at all to 4=extremely). 6 summary scores are calculated: Tension/Anxiety, Depression/Rejection, Anger/Hostility, Vigor/Activity, Fatigue/Inertia, and Confusion/Bewilderment; and range from 0-20 (higher scores = more negative mood state). Analysis of this endpoint is based on the change from baseline (BL) (EOMT score minus the BL score) using an ANCOVA model with BL value, BMI, grouped center as covariates.
Time Frame
Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Alabaster
State/Province
Alabama
ZIP/Postal Code
35007
Country
United States
Facility Name
GSK Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
GSK Investigational Site
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36303
Country
United States
Facility Name
GSK Investigational Site
City
Hoover
State/Province
Alabama
ZIP/Postal Code
35216
Country
United States
Facility Name
GSK Investigational Site
City
Jasper
State/Province
Alabama
ZIP/Postal Code
35501
Country
United States
Facility Name
GSK Investigational Site
City
Muscle Shoals
State/Province
Alabama
ZIP/Postal Code
35662
Country
United States
Facility Name
GSK Investigational Site
City
Northport
State/Province
Alabama
ZIP/Postal Code
35476
Country
United States
Facility Name
GSK Investigational Site
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35406
Country
United States
Facility Name
GSK Investigational Site
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85210
Country
United States
Facility Name
GSK Investigational Site
City
Peoria
State/Province
Arizona
ZIP/Postal Code
85381 - 4828
Country
United States
Facility Name
GSK Investigational Site
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85282
Country
United States
Facility Name
GSK Investigational Site
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71901
Country
United States
Facility Name
GSK Investigational Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
GSK Investigational Site
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
GSK Investigational Site
City
Concord
State/Province
California
ZIP/Postal Code
94520
Country
United States
Facility Name
GSK Investigational Site
City
Escondido
State/Province
California
ZIP/Postal Code
92026
Country
United States
Facility Name
GSK Investigational Site
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
GSK Investigational Site
City
Huntington Park
State/Province
California
ZIP/Postal Code
90255
Country
United States
Facility Name
GSK Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
GSK Investigational Site
City
Los Gatos
State/Province
California
ZIP/Postal Code
95032
Country
United States
Facility Name
GSK Investigational Site
City
Mission Viejo
State/Province
California
ZIP/Postal Code
92691
Country
United States
Facility Name
GSK Investigational Site
City
Newport Beach
State/Province
California
ZIP/Postal Code
92660
Country
United States
Facility Name
GSK Investigational Site
City
Northridge
State/Province
California
ZIP/Postal Code
91325
Country
United States
Facility Name
GSK Investigational Site
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
GSK Investigational Site
City
Riverside
State/Province
California
ZIP/Postal Code
92506
Country
United States
Facility Name
GSK Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92117
Country
United States
Facility Name
GSK Investigational Site
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
GSK Investigational Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
GSK Investigational Site
City
Temecula
State/Province
California
ZIP/Postal Code
92591
Country
United States
Facility Name
GSK Investigational Site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
GSK Investigational Site
City
Westlake Village
State/Province
California
ZIP/Postal Code
91361
Country
United States
Facility Name
GSK Investigational Site
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
Facility Name
GSK Investigational Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
GSK Investigational Site
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
GSK Investigational Site
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
Facility Name
GSK Investigational Site
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
GSK Investigational Site
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
GSK Investigational Site
City
New Port Richey
State/Province
Florida
ZIP/Postal Code
34652
Country
United States
Facility Name
GSK Investigational Site
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
GSK Investigational Site
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
GSK Investigational Site
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
GSK Investigational Site
City
St. Petersburg
State/Province
Florida
ZIP/Postal Code
33702
Country
United States
Facility Name
GSK Investigational Site
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
GSK Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
GSK Investigational Site
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
GSK Investigational Site
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
GSK Investigational Site
City
Roswell
State/Province
Georgia
ZIP/Postal Code
30076
Country
United States
Facility Name
GSK Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
GSK Investigational Site
City
Libertyville
State/Province
Illinois
ZIP/Postal Code
60048
Country
United States
Facility Name
GSK Investigational Site
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47713
Country
United States
Facility Name
GSK Investigational Site
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47714
Country
United States
Facility Name
GSK Investigational Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67207
Country
United States
Facility Name
GSK Investigational Site
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20852
Country
United States
Facility Name
GSK Investigational Site
City
Wellesley Hills
State/Province
Massachusetts
ZIP/Postal Code
02481
Country
United States
Facility Name
GSK Investigational Site
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
GSK Investigational Site
City
Olive Branch
State/Province
Mississippi
ZIP/Postal Code
38654
Country
United States
Facility Name
GSK Investigational Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
GSK Investigational Site
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
GSK Investigational Site
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63117
Country
United States
Facility Name
GSK Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89016
Country
United States
Facility Name
GSK Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89119
Country
United States
Facility Name
GSK Investigational Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
GSK Investigational Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87108
Country
United States
Facility Name
GSK Investigational Site
City
Flushing
State/Province
New York
ZIP/Postal Code
11365
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10128
Country
United States
Facility Name
GSK Investigational Site
City
North Massapequa
State/Province
New York
ZIP/Postal Code
11758
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14609
Country
United States
Facility Name
GSK Investigational Site
City
Staten Island
State/Province
New York
ZIP/Postal Code
10301
Country
United States
Facility Name
GSK Investigational Site
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
Facility Name
GSK Investigational Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
GSK Investigational Site
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
Facility Name
GSK Investigational Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
Facility Name
GSK Investigational Site
City
Norman
State/Province
Oklahoma
ZIP/Postal Code
73071
Country
United States
Facility Name
GSK Investigational Site
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97404
Country
United States
Facility Name
GSK Investigational Site
City
Medford
State/Province
Oregon
ZIP/Postal Code
97501
Country
United States
Facility Name
GSK Investigational Site
City
Levittown
State/Province
Pennsylvania
ZIP/Postal Code
19056
Country
United States
Facility Name
GSK Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15243
Country
United States
Facility Name
GSK Investigational Site
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29651
Country
United States
Facility Name
GSK Investigational Site
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
GSK Investigational Site
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78238
Country
United States
Facility Name
GSK Investigational Site
City
Alexandria
State/Province
Virginia
ZIP/Postal Code
22311
Country
United States
Facility Name
GSK Investigational Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
GSK Investigational Site
City
Weber City
State/Province
Virginia
ZIP/Postal Code
24290
Country
United States
Facility Name
GSK Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
GSK Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
Facility Name
GSK Investigational Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
GSK Investigational Site
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98664
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23186035
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.
Results Reference
derived
Learn more about this trial
A Study In Patients With Neuropathic Pain From Diabetic Peripheral Neuropathy (DPN)
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