A Clinical Study in Subjects With Neuropathic Pain From Post-Herpetic Neuralgia (PHN) Who Have Had an Inadequate Response to Gabapentin Treatment - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Crossover Assignment; Masking: Double Blind (Subject, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Neuralgia, Postherpetic
Interventions:	Drug: GEn 1200mg/day Drug: GEn 3600mg/day

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants (par.) were enrolled in a two-week Baseline Period, which included treatment with 1800 milligrams (mg)/day gabapentin. Participants who met entry criteria were then randomized. Inv., investigator.

Reporting Groups

	Description
GEn 1200 mg/Day Followed by GEn 3600 mg/Day	Gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, 1200 mg/day administered for 28 days, followed by a 4-day crossover period during which participants received GEn 2400 mg/day. After the crossover period, participants switched to a dose of 3600 mg/day for 28 days. After completion of the second treatment period, participants entered a down-titration period in which they received 1200 mg/day for 3 days, followed by 600 mg/ day for 3 days.
GEn 3600 mg/Day Followed by GEn 1200 mg/Day	GEn 3600 mg/day administered for 28 days, followed by a 4-day crossover period during which participants received GEn 2400 mg/day. After the crossover period, participants switched to a dose of 1200 mg/day for 28 days. After completion of the second treatment period, participants entered a down-titration period in which they received 2400 mg/day for 2 days, followed by 1200 mg/day for 2 days, followed by 600 mg/day for 2 days.

Description

GEn 1200 mg/Day Followed by GEn 3600 mg/Day

Gabapentin enacarbil (XP13512/GSK1838262), hereafter referred to as GEn, 1200 mg/day administered for 28 days, followed by a 4-day crossover period during which participants received GEn 2400 mg/day. After the crossover period, participants switched to a dose of 3600 mg/day for 28 days. After completion of the second treatment period, participants entered a down-titration period in which they received 1200 mg/day for 3 days, followed by 600 mg/ day for 3 days.

GEn 3600 mg/Day Followed by GEn 1200 mg/Day

GEn 3600 mg/day administered for 28 days, followed by a 4-day crossover period during which participants received GEn 2400 mg/day. After the crossover period, participants switched to a dose of 1200 mg/day for 28 days. After completion of the second treatment period, participants entered a down-titration period in which they received 2400 mg/day for 2 days, followed by 1200 mg/day for 2 days, followed by 600 mg/day for 2 days.

Participant Flow for 4 periods

Period 1: First Treatment Intervention Period

	GEn 1200 mg/Day Followed by GEn 3600 mg/Day	GEn 3600 mg/Day Followed by GEn 1200 mg/Day
STARTED	52 ^[1]	44
COMPLETED	42	41
NOT COMPLETED	10	3
Adverse Event	2	0
Lack of Efficacy	1	0
Protocol Violation	2	1
Lost to Follow-up	0	1
Investigator Discretion	1	1
Withdrawal by Subject	4	0

[1]	2 par. (1 withdrawal due to inv. discretion, 1 withdrawal by subject) did not take study drug.

Period 2: 4-Day Crossover Period

	GEn 1200 mg/Day Followed by GEn 3600 mg/Day	GEn 3600 mg/Day Followed by GEn 1200 mg/Day
STARTED	42	40 ^[1]
COMPLETED	41	40
NOT COMPLETED	1	0
Withdrawal by Subject	1	0

[1]	One 3600:1200 participant skipped the Crossover period, going directly to second Treatment Period.

Period 3: Second Treatment Intervention Period

	GEn 1200 mg/Day Followed by GEn 3600 mg/Day	GEn 3600 mg/Day Followed by GEn 1200 mg/Day
STARTED	41	41
COMPLETED	41	37
NOT COMPLETED	0	4
Adverse Event	0	1
Lack of Efficacy	0	3

Period 4: 6-Day Down-Titration Period

	GEn 1200 mg/Day Followed by GEn 3600 mg/Day	GEn 3600 mg/Day Followed by GEn 1200 mg/Day
STARTED	41	37
COMPLETED	39	35
NOT COMPLETED	2	2
Withdrawal by Subject	1	0
Did Not Attend Down-titration Visit	1	2

Baseline Characteristics

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Reporting Groups

	Description
All Participants in the Intent-to-Treat Population	All randomized participants who took at least one dose of study drug and had at least one post-baseline efficacy assessment, summarized independent of treatment sequence.

Baseline Measures

	All Participants in the Intent-to-Treat Population
Number of Participants [units: participants]	93
Age ^[1] [units: Years] Mean ± Standard Deviation	63 ± 12.15
Gender ^[2] [units: Participants]
Female	36
Male	57
Race/Ethnicity, Customized ^[3] [units: participants]
African American/African Heritage	18
White	74
American Indian or Alaska Native & White	1

[1]	Age (years) data were collected for all participants at the beginning of the Baseline period. Participants were not included in the Intent-to-Treat (ITT) Population unless they had an average baseline pain rating of 4, were randomized, took at least one dose of investigational product and completed one post-baseline efficacy assessment.
[2]	Gender data were collected for all participants at the beginning of the Baseline period. Participants were not included in the Intent-to-Treat (ITT) Population unless they had an average baseline pain rating of 4, were randomized, took at least one dose of investigational product and completed one post-baseline efficacy assessment.
[3]	Race data were collected for all participants at the beginning of the Baseline period. Participants were not included in the Intent-to-Treat (ITT) Population unless they had an average baseline pain rating of 4, were randomized, took at least one dose of investigational product and completed one post-baseline efficacy assessment.

Outcome Measures

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1. Primary:

Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using Last Observation Carried Forward (LOCF) Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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2. Primary:

Change From Baseline in the Mean 24-hour Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data for Each Treatment Period [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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3. Secondary:

Change From Baseline in the Mean Day-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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4. Secondary:

Change From Baseline in the Mean Day-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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5. Secondary:

Change From Baseline in the Mean Current (Evening) Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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6. Secondary:

Change From Baseline in the Mean Night-time Average Pain Intensity (API) Score at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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7. Secondary:

Change From Baseline in the Mean Night-time Worst Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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8. Secondary:

Change From Baseline in the Mean Current Morning Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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9. Secondary:

Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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10. Secondary:

Number of Participants Achieving Various Levels of Percent Reduction From Baseline in the Mean 24-hour Average Pain Intensity Score at the Last Week of Each Treatment Period Using LOCF Data by Period [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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11. Secondary:

Change From Baseline in the Mean Daily Dose in Milligrams of Rescue Medication at the Last Week of Each Treatment Period [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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12. Secondary:

Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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13. Secondary:

Number of Participants Who Are Responders on the Patient Global Impression of Change (PGIC) Questionnaire at the Last Week of Each Treatment Period Presented by Period Using LOCF Data [ Time Frame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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14. Secondary:

Number of Participants Who Are Responders on the Clinical Global Impression of Change (CGIC) Questionnaire at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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15. Secondary:

Number of Participants Who Are Responders on the Clinical Global Impression of Change (CGIC) Questionnaire at the Last Week of Each Treatment Period Presented by Period Using LOCF Data [ Time Frame: End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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16. Secondary:

Change From Baseline in the Mean Sleep Interference Score at the Last Week of Each Treatment Period Using LOCF Data [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of each treatment period) ]

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17. Secondary:

Change From Baseline in the Severity of Pain and the Impact of Pain as Assessed by the Brief Pain Inventory (BPI) at the Last Week of Each Treatment Period Using LOCF [ Time Frame: Baseline and End of Treatment (Weeks 4 and 9, representing the last week of treatment) ]

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18. Secondary:

Mean Gabapentin Steady-State (ss) Average, Minimum and Maximum Concentrations [ Time Frame: A total of 10 blood samples (2 samples at each visit) were collected per participant at Baseline, and the Week 1 and Week 4 visits for each period ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00617461 History of Changes
Other Study ID Numbers:	110527
Study First Received:	February 6, 2008
Results First Received:	April 26, 2011
Last Updated:	October 13, 2011
Health Authority:	United States: Food and Drug Administration