A Study In Patients With Neuropathic Pain From Diabetic Peripheral Neuropathy (DPN)

• Sponsor: XenoPort, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00643760
• Collaborator: (none)
• Enrollment: 421
• Locations: 90
• Arms: 5
• Duration (Months): 11.1
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.4

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Neuropathy, Diabetic	Drug: Placebo; Drug: GEn 1200mg/day; Drug: GEn 2400mg/day; Drug: GEn 3600mg/day; Drug: Pregabalin	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 421 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: Mar 1, 2008
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo	Drug: Placebo; placebo
Other: Pregabalin Pregabalin 300mg/day (positive control), maintenance treatment 14 weeks	Drug: Pregabalin; pregabalin 300mg/day
Experimental: GEn 1200mg/day gabapentin enacarbil 1200mg/day, maintenance treatment 14 weeks	Drug: GEn 1200mg/day; gabapentin enacarbil 1200mg/day; Other Names: XP13512 GSK1838262 gabapentin enacarbil
Experimental: GEn 2400mg/day gabapentin enacarbil 2400mg/day, maintenance treatment 14 weeks	Drug: GEn 2400mg/day; gabapentin enacarbil 2400mg/day; Other Names: gabapentin enacarbil GSK1838262 XP13512
Experimental: GEn 3600mg/day gabapentin enacarbil 3600mg/day, maintanance treatment 14 weeks	Drug: GEn 3600mg/day; gabapentin enacarbil 3600mg/day; Other Names: XP13512 GSK1838262 gabapentin enacarbil

Outcome Measures

Primary Outcome Measures

1. 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 (representing the earliest date of Week 13 visit/withdrawal visit)]

   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

1. Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

2. Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

3. Change From Baseline in the Mean Current (Morning) Pain Intensity Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

4. Change From Baseline in the Mean Current (Evening) Pain Intensity Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

5. Change From Baseline in the Mean Day-time Worst Pain Intensity Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

6. Change From Baseline in the Mean Night-time Worst Pain Intensity Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

7. Change From Baseline in the Mean Sleep Interference Score at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

8. Change From Baseline in the Mean Daily Dose of Rescue Medication at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

9. Change From Baseline in Pain Quality as Assessed by the Neuropathic Pain Scale (NPS) Summary Scores at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

   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.

10. Change From Baseline in Pain Characteristics and Intensity as Assessed by the Short Form-McGill Pain Questionnaire (SF-MPQ) at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

11. Change From Baseline in Pain Score After Taking a 50-foot Walk at EOMT [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

12. Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at EOMT Using LOCF Data [EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

13. Number of Participants Who Are Responders on the Clinician Global Impression of Change (CGIC) Questionnaire at EOMT Using LOCF Data [EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

14. 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 (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

15. Time to Onset of Sustained Improvement in the 24-hour Average Pain Intensity Score [Any time post-baseline until date of last dose of study medication (up to Week 13)]

    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.

16. 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 [Baseline and EOMT]

    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.

17. Change From Baseline in Quality of Life as Assessed by the 36-Item Short Form Health Survey (SF-36) at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

18. Change From Baseline in Emotional Functioning as Assessed by the Profile of Mood States-Brief Form (POMS-B) at EOMT Using LOCF Data [Baseline and EOMT (representing the earliest date of Week 13 visit/withdrawal visit)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Alabaster	Alabama	United States	35007
2	GSK Investigational Site	Birmingham	Alabama	United States	35205
3	GSK Investigational Site	Dothan	Alabama	United States	36303
4	GSK Investigational Site	Hoover	Alabama	United States	35216
5	GSK Investigational Site	Jasper	Alabama	United States	35501
6	GSK Investigational Site	Muscle Shoals	Alabama	United States	35662
7	GSK Investigational Site	Northport	Alabama	United States	35476
8	GSK Investigational Site	Tuscaloosa	Alabama	United States	35406
9	GSK Investigational Site	Mesa	Arizona	United States	85210
10	GSK Investigational Site	Peoria	Arizona	United States	85381 - 4828
11	GSK Investigational Site	Tempe	Arizona	United States	85282
12	GSK Investigational Site	Hot Springs	Arkansas	United States	71901
13	GSK Investigational Site	Little Rock	Arkansas	United States	72205
14	GSK Investigational Site	Anaheim	California	United States	92801
15	GSK Investigational Site	Concord	California	United States	94520
16	GSK Investigational Site	Escondido	California	United States	92026
17	GSK Investigational Site	Fresno	California	United States	93720
18	GSK Investigational Site	Huntington Park	California	United States	90255
19	GSK Investigational Site	La Jolla	California	United States	92037
20	GSK Investigational Site	Los Gatos	California	United States	95032
21	GSK Investigational Site	Mission Viejo	California	United States	92691
22	GSK Investigational Site	Newport Beach	California	United States	92660
23	GSK Investigational Site	Northridge	California	United States	91325
24	GSK Investigational Site	Oxnard	California	United States	93030
25	GSK Investigational Site	Riverside	California	United States	92506
26	GSK Investigational Site	San Diego	California	United States	92117
27	GSK Investigational Site	Santa Ana	California	United States	92705
28	GSK Investigational Site	Santa Monica	California	United States	90404
29	GSK Investigational Site	Temecula	California	United States	92591
30	GSK Investigational Site	Walnut Creek	California	United States	94598
31	GSK Investigational Site	Westlake Village	California	United States	91361
32	GSK Investigational Site	Brandon	Florida	United States	33511
33	GSK Investigational Site	Clearwater	Florida	United States	33765
34	GSK Investigational Site	Fort Lauderdale	Florida	United States	33308
35	GSK Investigational Site	Fort Myers	Florida	United States	33916
36	GSK Investigational Site	Hallandale Beach	Florida	United States	33009
37	GSK Investigational Site	Hollywood	Florida	United States	33021
38	GSK Investigational Site	New Port Richey	Florida	United States	34652
39	GSK Investigational Site	Ocala	Florida	United States	34471
40	GSK Investigational Site	Ormond Beach	Florida	United States	32174
41	GSK Investigational Site	Pembroke Pines	Florida	United States	33024
42	GSK Investigational Site	St. Petersburg	Florida	United States	33702
43	GSK Investigational Site	Tallahassee	Florida	United States	32308
44	GSK Investigational Site	Atlanta	Georgia	United States	30308
45	GSK Investigational Site	Decatur	Georgia	United States	30033
46	GSK Investigational Site	Marietta	Georgia	United States	30060
47	GSK Investigational Site	Roswell	Georgia	United States	30076
48	GSK Investigational Site	Chicago	Illinois	United States	60637
49	GSK Investigational Site	Libertyville	Illinois	United States	60048
50	GSK Investigational Site	Evansville	Indiana	United States	47713
51	GSK Investigational Site	Evansville	Indiana	United States	47714
52	GSK Investigational Site	Wichita	Kansas	United States	67207
53	GSK Investigational Site	Rockville	Maryland	United States	20852
54	GSK Investigational Site	Wellesley Hills	Massachusetts	United States	02481
55	GSK Investigational Site	Kalamazoo	Michigan	United States	49048
56	GSK Investigational Site	Olive Branch	Mississippi	United States	38654
57	GSK Investigational Site	Kansas City	Missouri	United States	64111
58	GSK Investigational Site	St. Louis	Missouri	United States	63110
59	GSK Investigational Site	St. Louis	Missouri	United States	63117
60	GSK Investigational Site	Las Vegas	Nevada	United States	89016
61	GSK Investigational Site	Las Vegas	Nevada	United States	89119
62	GSK Investigational Site	Albuquerque	New Mexico	United States	87106
63	GSK Investigational Site	Albuquerque	New Mexico	United States	87108
64	GSK Investigational Site	Flushing	New York	United States	11365
65	GSK Investigational Site	New York	New York	United States	10128
66	GSK Investigational Site	North Massapequa	New York	United States	11758
67	GSK Investigational Site	Rochester	New York	United States	14609
68	GSK Investigational Site	Staten Island	New York	United States	10301
69	GSK Investigational Site	Greensboro	North Carolina	United States	27408
70	GSK Investigational Site	Raleigh	North Carolina	United States	27607
71	GSK Investigational Site	Salisbury	North Carolina	United States	28144
72	GSK Investigational Site	Toledo	Ohio	United States	43623
73	GSK Investigational Site	Norman	Oklahoma	United States	73071
74	GSK Investigational Site	Eugene	Oregon	United States	97404
75	GSK Investigational Site	Medford	Oregon	United States	97501
76	GSK Investigational Site	Levittown	Pennsylvania	United States	19056
77	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15243
78	GSK Investigational Site	Greer	South Carolina	United States	29651
79	GSK Investigational Site	Mount Pleasant	South Carolina	United States	29464
80	GSK Investigational Site	Kingsport	Tennessee	United States	37660
81	GSK Investigational Site	Houston	Texas	United States	77030
82	GSK Investigational Site	San Antonio	Texas	United States	78229
83	GSK Investigational Site	San Antonio	Texas	United States	78238
84	GSK Investigational Site	Alexandria	Virginia	United States	22311
85	GSK Investigational Site	Richmond	Virginia	United States	23249
86	GSK Investigational Site	Weber City	Virginia	United States	24290
87	GSK Investigational Site	Spokane	Washington	United States	99202
88	GSK Investigational Site	Spokane	Washington	United States	99208
89	GSK Investigational Site	Tacoma	Washington	United States	98405
90	GSK Investigational Site	Vancouver	Washington	United States	98664

Sponsors and Collaborators

• XenoPort, Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: XenoPort, Inc.
• ClinicalTrials.gov Identifier: NCT00643760
• Other Study ID Numbers: 110448
• First Posted: Mar 26, 2008
• Last Update Posted: Jul 22, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by XenoPort, Inc.: Peripheral Diabetic Neuropathy (PDN); Neuropathic Pain
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies; Pregabalin; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Period Title: Overall Study
STARTED	120	62	56	117	66
Safety Population/Treated With Drug	120	62	56	116	66
ITT Population	120	62	56	116	66
COMPLETED	90	47	37	79	47
NOT COMPLETED	30	15	19	38	19

Baseline Characteristics

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day	Total
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).	Total of all reporting groups
Overall Participants	120	62	56	116	66	420
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.1 (10.63)	57.5 (10.32)	60.8 (8.97)	57.5 (9.87)	57.7 (10.59)	58.7 (10.20)
Sex: Female, Male (Count of Participants)
Female	47 39.2%	28 45.2%	19 33.9%	45 38.8%	32 48.5%	171 40.7%
Male	73 60.8%	34 54.8%	37 66.1%	71 61.2%	34 51.5%	249 59.3%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	20 16.7%	15 24.2%	7 12.5%	20 17.2%	12 18.2%	74 17.6%
American Indian or Alaskan Native	2 1.7%	0 0%	0 0%	0 0%	0 0%	2 0.5%
Asian - Central/South Asian Heritage	0 0%	0 0%	0 0%	1 0.9%	0 0%	1 0.2%
Asian - South East Asian Heritage	0 0%	1 1.6%	0 0%	2 1.7%	0 0%	3 0.7%
White - Arabic/North African Heritage	0 0%	2 3.2%	2 3.6%	1 0.9%	0 0%	5 1.2%
White - White/Caucasian/European Heritage	98 81.7%	44 71%	45 80.4%	89 76.7%	52 78.8%	328 78.1%
Mixed Race	0 0%	0 0%	1 1.8%	1 0.9%	0 0%	2 0.5%
Not Provided	0 0%	0 0%	1 1.8%	2 1.7%	2 3%	5 1.2%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
Least Squares Mean (Standard Error) [scores on a scale]	-2.08 (0.196)	-2.43 (0.274)	-2.10 (0.289)	-2.63 (0.202)	-1.65 (0.266)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GEn 1200 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.295
	Comments	This p-value has been adjusted for multiplicity using a combination of a sequential method and the Hochberg procedure in order to maintain the overall experiment-wise alpha level of 0.05.
	Method	ANCOVA
	Comments	Analysis of covariance (ANCOVA) model with body mass index (BMI), baseline 24-hour average pain intensity, and grouped center as covariates was used.
Method of Estimation	Estimation Parameter	Adjusted mean difference versus placebo
	Estimated Value	-0.35
	Confidence Interval	() 95%; -1.02 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GEn 2400 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.946
	Comments	This p-value has been adjusted for multiplicity using a combination of a sequential method and the Hochberg procedure in order to maintain the overall experiment-wise alpha level of 0.05.
	Method	ANCOVA
	Comments	An ANCOVA model with BMI, baseline 24-hour average pain intensity, and grouped center as covariates was used.
Method of Estimation	Estimation Parameter	Adjusted mean difference versus placebo
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.71 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GEn 3600 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments	This p-value has been adjusted for multiplicity using a combination of a sequential method and the Hochberg procedure in order to maintain the overall experiment-wise alpha level of 0.05.
	Method	ANCOVA
	Comments	An ANCOVA model with BMI, baseline 24-hour average pain intensity, and grouped center as covariates was used.
Method of Estimation	Estimation Parameter	Adjusted mean difference versus placebo
	Estimated Value	-0.55
	Confidence Interval	() 95%; -1.10 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, PGB 300 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference versus placebo
	Estimated Value	0.43
	Confidence Interval	() 95%; -0.22 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
Least Squares Mean (Standard Error) [scores on a scale]	-2.07 (0.195)	-2.35 (0.272)	-2.06 (0.286)	-2.54 (0.200)	-1.50 (0.264)

3. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. There were two participants in the GEn 3600 mg/day group who did not complete enough post-baseline morning diaries to calculate an average night-time pain intensity score for the EOMT timepoint.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	114	66
Least Squares Mean (Standard Error) [scores on a scale]	-1.99 (0.203)	-2.15 (0.282)	-2.04 (0.298)	-2.71 (0.210)	-1.83 (0.274)

4. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. There were two participants in the GEn 3600 mg/day group who did not complete enough post-baseline morning diaries to calculate a current (morning) pain intensity score for the EOMT timepoint.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	114	66
Least Squares Mean (Standard Error) [scores on a scale]	-1.90 (0.192)	-2.08 (0.268)	-1.95 (0.282)	-2.40 (0.199)	-1.50 (0.260)

5. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
Least Squares Mean (Standard Error) [scores on a scale]	-2.19 (0.194)	-2.24 (0.271)	-2.10 (0.285)	-2.66 (0.200)	-1.65 (0.264)

6. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
Least Squares Mean (Standard Error) [scores on a scale]	-2.33 (0.210)	-2.35 (0.292)	-2.25 (0.307)	-2.88 (0.215)	-1.62 (0.284)

7. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. There were two participants in the GEn 3600 mg/day group who did not complete enough post-baseline morning diaries to calculate a night-time worst pain intensity score for the EOMT timepoint.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	114	66
Least Squares Mean (Standard Error) [scores on a scale]	-2.25 (0.213)	-2.24 (0.297)	-2.25 (0.313)	-3.00 (0.221)	-1.86 (0.289)

8. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. There were two participants in the GEn 3600 mg/day group who did not complete enough post-baseline morning diaries to calculate a night-time worst pain intensity score for the EOMT timepoint.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	114	66
Least Squares Mean (Standard Error) [scores on a scale]	-2.35 (0.214)	-2.54 (0.298)	-2.45 (0.313)	-3.01 (0.221)	-2.24 (0.289)

9. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
Least Squares Mean (Standard Error) [milligrams]	-261.99 (73.630)	-171.64 (102.482)	-102.51 (107.918)	-228.54 (76.139)	-246.07 (99.758)

10. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed an NPS assessment at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	112	58	45	108	62
NPS 10 Score	-18.92 (1.914)	-18.43 (2.658)	-22.24 (3.027)	-25.49 (1.970)	-16.16 (2.576)
NPS 8 Score	-18.73 (1.898)	-17.83 (2.637)	-21.84 (3.003)	-25.14 (1.954)	-16.19 (2.555)
NPS Non-Allodynic Score	-19.37 (1.998)	-18.89 (2.776)	-22.86 (3.160)	-26.35 (2.057)	-15.63 (2.690)
NPS 4 Score	-20.54 (2.120)	-20.90 (2.944)	-25.15 (3.352)	-27.84 (2.182)	-16.06 (2.853)

11. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed an SF-MPQ assessment at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	112	57	44	108	62
SF-MPQ Total Score	-5.85 (0.865)	-6.55 (1.214)	-6.75 (1.381)	-7.56 (0.888)	-4.01 (1.161)
SF-MPQ Sensory Score	-4.25 (0.674)	-4.83 (0.946)	-5.31 (1.077)	-5.50 (0.692)	-2.73 (0.906)
SF-MPQ Affective Score	-1.63 (0.247)	-1.65 (0.348)	-1.45 (0.395)	-2.07 (0.254)	-1.26 (0.332)

12. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed a 50-foot walk at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	111	57	44	107	59
Least Squares Mean (Standard Error) [scores on a scale]	-2.38 (0.077)	-2.32 (0.107)	-2.36 (0.122)	-2.52 (0.080)	-2.17 (0.106)

13. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed a PGIC assessment at Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	112	58	46	108	62
Number [participants]	46 38.3%	22 35.5%	24 42.9%	53 45.7%	62 93.9%

14. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants had a CGIC assessment at Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	98	52	40	89	54
Number [participants]	39 32.5%	20 32.3%	22 39.3%	50 43.1%	17 25.8%

15. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
>= 0% reduction from baseline	103 85.8%	55 88.7%	50 89.3%	101 87.1%	55 83.3%
>= 10% reduction from baseline	86 71.7%	43 69.4%	42 75%	91 78.4%	42 63.6%
>= 20% reduction from baseline	73 60.8%	36 58.1%	34 60.7%	78 67.2%	36 54.5%
>= 30% reduction from baseline	57 47.5%	31 50%	25 44.6%	66 56.9%	28 42.4%
>= 40% reduction from baseline	46 38.3%	28 45.2%	19 33.9%	55 47.4%	20 30.3%
>= 50% reduction from baseline	35 29.2%	26 41.9%	15 26.8%	46 39.7%	14 21.2%
>= 60% reduction from baseline	26 21.7%	21 33.9%	11 19.6%	41 35.3%	9 13.6%
>= 70% reduction from baseline	15 12.5%	17 27.4%	6 10.7%	25 21.6%	5 7.6%
>= 80% reduction from baseline	11 9.2%	11 17.7%	5 8.9%	17 14.7%	4 6.1%
>= 90% reduction from baseline	4 3.3%	5 8.1%	2 3.6%	8 6.9%	3 4.5%
100% reduction from baseline	3 2.5%	4 6.5%	1 1.8%	5 4.3%	3 4.5%

16. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	120	62	56	116	66
Median (Full Range) [days]	24	25	22	15	29

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed a BPI assessment at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	112	57	44	107	62
Brief Pain Inventory Severity of Pain	-2.1 (0.21)	-2.3 (0.29)	-2.4 (0.33)	-2.8 (0.21)	-1.7 (0.28)
Brief Pain Inventory Interference of Pain	-2.0 (0.21)	-2.0 (0.30)	-2.1 (0.34)	-2.5 (0.22)	-1.9 (0.29)

18. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed an SF-36 at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	112	57	44	107	61
SF-36 Physical Component Summary Score	3.1 (0.67)	3.5 (0.93)	3.7 (1.06)	4.6 (0.69)	3.7 (0.90)
SF-36 Mental Component Summary Score	2.5 (0.88)	0.4 (1.24)	1.5 (1.41)	1.6 (0.91)	0.7 (1.20)

19. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

ITT Population. Not all participants completed a POMS-B at both Baseline and Week 13/Withdrawal; as such, the number analyzed is different from the full ITT Population counts.

Arm/Group Title	Placebo	GEn 1200 mg/Day	GEn 2400 mg/Day	GEn 3600 mg/Day	PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).	One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).	Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
Measure Participants	112	57	44	107	61
Tension/Anxiety Domain Score	-1.0 (0.29)	-0.6 (0.41)	-0.7 (0.47)	-0.9 (0.30)	-0.3 (0.40)
Depression/Rejection Domain Score	-0.5 (0.30)	-0.2 (0.43)	-0.6 (0.49)	-0.3 (0.32)	0.4 (0.41)
Anger/Hostility Domain Score	-0.5 (0.32)	-0.8 (0.45)	-0.5 (0.51)	-0.3 (0.33)	-0.3 (0.44)
Vigor/Activity Domain Score	0.6 (0.32)	-0.1 (0.45)	0.1 (0.51)	0.7 (0.33)	-0.4 (0.44)
Fatigue/Inertia Domain Score	-0.8 (0.37)	-0.5 (0.52)	-1.1 (0.59)	-1.1 (0.38)	-0.1 (0.50)
Confusion/Bewilderment Domain Score	-0.3 (0.21)	0.2 (0.29)	-0.1 (0.33)	0.0 (0.22)	-0.2 (0.28)

Adverse Events

Adverse Event Reporting Description	Adverse events (AEs) and serious adverse events (SAEs) were captured for all participants in the Safety Population, comprised of all randomized participants who took at least one dose of investigational product.
Arm/Group Title	Placebo		GEn 1200 mg/Day		GEn 2400 mg/Day		GEn 3600 mg/Day		PGB 300 mg/Day
Arm/Group Description	Three 600 milligram (mg) gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, placebo tablets taken orally twice daily (morning and evening); one 100 mg pregabalin (PGB) placebo capsule taken orally three times daily (morning, midday, and evening).		One 600 mg extended release (ER) GEn tablet and two 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).		Two 600 mg ER GEn tablets and one 600 mg GEn placebo tablet taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).		Three 600 mg ER GEn tablets taken orally twice daily (morning and evening); one 100 mg PGB placebo capsule taken orally three times daily (morning, midday, and evening).		Three 600 mg GEn placebo tablets taken orally twice daily (morning and evening); one 100 mg PGB capsule taken orally three times daily (morning, midday, and evening).
All Cause Mortality
	Placebo		GEn 1200 mg/Day		GEn 2400 mg/Day		GEn 3600 mg/Day		PGB 300 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		GEn 1200 mg/Day		GEn 2400 mg/Day		GEn 3600 mg/Day		PGB 300 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/120 (5%)		3/62 (4.8%)		4/56 (7.1%)		5/116 (4.3%)		2/66 (3%)
Cardiac disorders
Angina pectoris	0/120 (0%)		0/62 (0%)		0/56 (0%)		1/116 (0.9%)		0/66 (0%)
Coronary artery stenosis	0/120 (0%)		0/62 (0%)		0/56 (0%)		1/116 (0.9%)		0/66 (0%)
Sinus tachycardia	1/120 (0.8%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Supraventricular tachycardia	1/120 (0.8%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
General disorders
Chest pain	1/120 (0.8%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Oedema peripheral	0/120 (0%)		0/62 (0%)		0/56 (0%)		1/116 (0.9%)		0/66 (0%)
Hepatobiliary disorders
Cholecystitis	0/120 (0%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		1/66 (1.5%)
Infections and infestations
Cellulitis	0/120 (0%)		1/62 (1.6%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Infected skin ulcer	0/120 (0%)		1/62 (1.6%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Injury, poisoning and procedural complications
Ankle fracture	0/120 (0%)		0/62 (0%)		1/56 (1.8%)		0/116 (0%)		0/66 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/120 (0%)		0/62 (0%)		1/56 (1.8%)		0/116 (0%)		0/66 (0%)
Hyperkalaemia	0/120 (0%)		0/62 (0%)		1/56 (1.8%)		0/116 (0%)		0/66 (0%)
Hypoglycaemia	0/120 (0%)		0/62 (0%)		0/56 (0%)		1/116 (0.9%)		0/66 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/120 (0%)		0/62 (0%)		0/56 (0%)		1/116 (0.9%)		0/66 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia	1/120 (0.8%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Nervous system disorders
Ataxia	0/120 (0%)		0/62 (0%)		0/56 (0%)		1/116 (0.9%)		0/66 (0%)
Dizziness	1/120 (0.8%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Partial seizures	0/120 (0%)		0/62 (0%)		1/56 (1.8%)		0/116 (0%)		0/66 (0%)
Syncope	1/120 (0.8%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Psychiatric disorders
Affective disorder	0/120 (0%)		0/62 (0%)		0/56 (0%)		0/116 (0%)		1/66 (1.5%)
Renal and urinary disorders
Renal failure	0/120 (0%)		0/62 (0%)		1/56 (1.8%)		0/116 (0%)		0/66 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/120 (0%)		1/62 (1.6%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/120 (0%)		0/62 (0%)		1/56 (1.8%)		0/116 (0%)		0/66 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/120 (0%)		1/62 (1.6%)		0/56 (0%)		0/116 (0%)		0/66 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		GEn 1200 mg/Day		GEn 2400 mg/Day		GEn 3600 mg/Day		PGB 300 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/120 (41.7%)		34/62 (54.8%)		25/56 (44.6%)		62/116 (53.4%)		32/66 (48.5%)
Eye disorders
Vision blurred	5/120 (4.2%)		0/62 (0%)		3/56 (5.4%)		2/116 (1.7%)		3/66 (4.5%)
Gastrointestinal disorders
Nausea	9/120 (7.5%)		7/62 (11.3%)		4/56 (7.1%)		7/116 (6%)		3/66 (4.5%)
Diarrhoea	6/120 (5%)		3/62 (4.8%)		2/56 (3.6%)		6/116 (5.2%)		5/66 (7.6%)
Constipation	4/120 (3.3%)		3/62 (4.8%)		4/56 (7.1%)		4/116 (3.4%)		6/66 (9.1%)
Dry mouth	4/120 (3.3%)		0/62 (0%)		4/56 (7.1%)		1/116 (0.9%)		1/66 (1.5%)
Vomiting	3/120 (2.5%)		3/62 (4.8%)		1/56 (1.8%)		2/116 (1.7%)		0/66 (0%)
General disorders
Oedema peripheral	5/120 (4.2%)		2/62 (3.2%)		0/56 (0%)		10/116 (8.6%)		11/66 (16.7%)
Fatigue	3/120 (2.5%)		3/62 (4.8%)		3/56 (5.4%)		5/116 (4.3%)		4/66 (6.1%)
Infections and infestations
Urinary tract infection	5/120 (4.2%)		3/62 (4.8%)		4/56 (7.1%)		6/116 (5.2%)		4/66 (6.1%)
Nasopharyngitis	5/120 (4.2%)		1/62 (1.6%)		2/56 (3.6%)		4/116 (3.4%)		3/66 (4.5%)
Bronchitis	1/120 (0.8%)		3/62 (4.8%)		1/56 (1.8%)		1/116 (0.9%)		1/66 (1.5%)
Injury, poisoning and procedural complications
Excoriation	0/120 (0%)		1/62 (1.6%)		1/56 (1.8%)		1/116 (0.9%)		3/66 (4.5%)
Fall	0/120 (0%)		3/62 (4.8%)		1/56 (1.8%)		1/116 (0.9%)		0/66 (0%)
Investigations
Weight increased	1/120 (0.8%)		0/62 (0%)		2/56 (3.6%)		5/116 (4.3%)		5/66 (7.6%)
Metabolism and nutrition disorders
Increased appetite	4/120 (3.3%)		0/62 (0%)		3/56 (5.4%)		1/116 (0.9%)		3/66 (4.5%)
Musculoskeletal and connective tissue disorders
Muscle spasms	4/120 (3.3%)		6/62 (9.7%)		0/56 (0%)		11/116 (9.5%)		3/66 (4.5%)
Arthralgia	5/120 (4.2%)		1/62 (1.6%)		2/56 (3.6%)		5/116 (4.3%)		3/66 (4.5%)
Pain in extremity	2/120 (1.7%)		1/62 (1.6%)		4/56 (7.1%)		6/116 (5.2%)		2/66 (3%)
Back pain	3/120 (2.5%)		1/62 (1.6%)		1/56 (1.8%)		3/116 (2.6%)		3/66 (4.5%)
Nervous system disorders
Dizziness	6/120 (5%)		9/62 (14.5%)		8/56 (14.3%)		16/116 (13.8%)		9/66 (13.6%)
Somnolence	5/120 (4.2%)		2/62 (3.2%)		7/56 (12.5%)		14/116 (12.1%)		9/66 (13.6%)
Headache	9/120 (7.5%)		3/62 (4.8%)		4/56 (7.1%)		4/116 (3.4%)		6/66 (9.1%)
Disturbance in attention	2/120 (1.7%)		2/62 (3.2%)		0/56 (0%)		2/116 (1.7%)		3/66 (4.5%)
Hypoaesthesia	1/120 (0.8%)		1/62 (1.6%)		1/56 (1.8%)		0/116 (0%)		3/66 (4.5%)
Paraesthesia	0/120 (0%)		2/62 (3.2%)		1/56 (1.8%)		0/116 (0%)		3/66 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.