A Comparison of EpiCept™ NP-1 Topical Cream vs. Oral Gabapentin in Postherpetic Neuralgia (PHN)

• ClinicalTrials.gov Identifier: NCT00475904
• Recruitment Status: Completed
• First Posted: May 21, 2007
• Results First Posted: July 6, 2011
• Last Update Posted: July 27, 2011
• Sponsor: EpiCept Corporation
• Information provided by: EpiCept Corporation

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Post Herpetic Neuralgia; PHN; Neuropathy; Nerve Pain
• Interventions: Drug: EpiCept-NP-1 Cream; Drug: Gabapentin Capsules; Drug: placebo
• Enrollment: 360

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules	Gabapentin Capsules, Placebo Cream	Placebo Cream and Capsules
Arm/Group Description	amitriptyline 4% ketamine 2% cream 4grams applied twice daily to affected area, placebo capsules taken orally 3 times daily	oral gabapentin capsules 600mg three times daily and placebo cream applied 4 grams twice daily	placebo NP-1 cream 4gms applied twice daily and placebo gabapentin capsules, taken orally 3 times daily
Period Title: Overall Study
Started	140	144	76
Completed	125	131	72
Not Completed	15	13	4

Baseline Characteristics

Arm/Group Title		Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules	Gabapentin Capsules, Placebo Cream	Placebo Cream and Capsules	Total
Arm/Group Description		amitriptyline 4% ketamine 2% cream 4grams applied twice daily to affected area, placebo capsules taken orally 3 times daily	oral gabapentin capsules 600mg three times daily and placebo cream applied 4 grams twice daily	placebo NP-1 cream 4gms applied twice daily and placebo gabapentin capsules, taken orally 3 times daily	Total of all reporting groups
Overall Number of Baseline Participants		140	144	76	360
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	140 participants	144 participants	76 participants	360 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	106 75.7%	109 75.7%	55 72.4%	270 75.0%
	>=65 years	34 24.3%	35 24.3%	21 27.6%	90 25.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	140 participants	144 participants	76 participants	360 participants
		51.3 (16.04)	53.2 (15.53)	53.2 (16.47)	52.5 (15.91)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	140 participants	144 participants	76 participants	360 participants
	Female	56 40.0%	49 34.0%	30 39.5%	135 37.5%
	Male	84 60.0%	95 66.0%	46 60.5%	225 62.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
India	Number Analyzed	140 participants	144 participants	76 participants	360 participants
		140	144	76	360

Outcome Measures

1. Primary Outcome

Title	Change in Pain Scores Comparing NP-1 Cream vs. Placebo Cream for Treatment of the Pain of Post Herpetic Neuralgia(PHN)From Baseline to 28 Days.
Description	Difference in pain scores between NP-1 cream vs. placebo cream for the treatment of the pain of PHN. Baseline pain scores were compared to the pain scores after 28 days of treatment. Pain scores were rated on a 11 point numerical rating scale (0-10) where 0 was no pain and 10 was worst possible pain.
Time Frame	baseline and 28 days

Outcome Measure Data

Analysis Population Description

This analysis was performed for the Intent To Treat (ITT) population using the ast Observation Carried Forward (LOCF) approach.

Arm/Group Title	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules	Gabapentin Capsules, Placebo Cream	Placebo Cream and Capsules
Arm/Group Description:	amitriptyline 4% ketamine 2% cream 4grams applied twice daily to affected area, placebo capsules taken orally 3 times daily	oral gabapentin capsules 600mg three times daily and placebo cream applied 4 grams twice daily	placebo NP-1 cream 4gms applied twice daily and placebo gabapentin capsules, taken orally 3 times daily
Overall Number of Participants Analyzed	135	138	76
Mean (95% Confidence Interval); Unit of Measure: units on a scale
	2.424; (2.07 to 2.78)	2.471; (2.17 to 2.77)	1.877; (1.43 to 2.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules, Placebo Cream and Capsules
	Comments	In the initial analysis, the efficacy of the test treatment NP-1 cream was compared with placebo using an analysis of variance (ANOVA). The analysis was conducted using the ITT population to compare the mean changes in pain scores from baseline to endpoint for the 2 treatments; the LOCF approach was employed for patients who did not complete the trial.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0441
	Comments	a priori threshold for statistical significance was p<0.05
	Method	ANOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.547
	Confidence Interval	(2-Sided) 95%; 0.01 to 1.08
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.2709
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Change in Pain Intensity From Baseline to 28 Days of Treatment, Comparison Between NP-1 Topical Cream and Oral Gabapentin
Description	Change in pain intensity scores between NP-1 cream vs. oral gabapentin for the treatment of the pain of PHN. Baseline pain scores were compared to the pain scores after 28 days of treatment. Pain scores were rated on a 11 point numerical rating scale (0-10) where 0 was no pain and 10 was worst possible pain.
Time Frame	baseline to 28 Days

Outcome Measure Data

Analysis Population Description

Intent To Treat (ITT) population using the Last Observation Carried Forward) LOCF imputation technique

Arm/Group Title	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules	Gabapentin Capsules, Placebo Cream	Placebo Cream and Capsules
Arm/Group Description:	amitriptyline 4% ketamine 2% cream 4grams applied twice daily to affected area, placebo capsules taken orally 3 times daily	oral gabapentin capsules 600mg three times daily and placebo cream applied 4 grams twice daily	placebo NP-1 cream 4gms applied twice daily and placebo gabapentin capsules, taken orally 3 times daily
Overall Number of Participants Analyzed	135	138	76
Least Squares Mean (95% Confidence Interval); Unit of Measure: units on a scale
	2.424; (2.07 to 2.7)	2.471; (2.17 to 2.77)	1.877; (1.43 to 2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules, Gabapentin Capsules, Placebo Cream
	Comments	the primary hypothesis of this study was that NP-1 topical cream (amitriptyline 4%/ketamine 2%) administered twice daily in doses of 4 gm for 4 weeks is not inferior to the standard treatment (oral gabapentin 600 mg 3 times daily) for relieving the pain of adult patients with PHN.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	To conclude that the NP-1 was not inferior to gabapentin, the upper limit of the 2-sided 90% CI for the difference between treatments for the endpoint mean pain score was required to be below the non-inferiority margin of 0.70.
Statistical Test of Hypothesis	P-Value	0.8409
	Comments	To conclude that the NP-1 was not inferior to gabapentin, the upper limit of the 2-sided 90% CI for the difference between treatments for the endpoint mean pain score was required to be below the non-inferiority margin of 0.70.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.046
	Confidence Interval	(2-Sided) 90%; -0.33 to 0.43
	Parameter Dispersion	Type: Standard Error of the mean; Value: .2311
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules		Gabapentin Capsules, Placebo Cream		Placebo Cream and Capsules
Arm/Group Description	amitriptyline 4% ketamine 2% cream 4grams applied twice daily to affected area, placebo capsules taken orally 3 times daily		oral gabapentin capsules 600mg three times daily and placebo cream applied 4 grams twice daily		placebo NP-1 cream 4gms applied twice daily and placebo gabapentin capsules, taken orally 3 times daily
All-Cause Mortality
	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules		Gabapentin Capsules, Placebo Cream		Placebo Cream and Capsules
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules		Gabapentin Capsules, Placebo Cream		Placebo Cream and Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/140 (0.00%)		0/144 (0.00%)		0/76 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Amitriptyline 4% Ketamine 2% Cream, Placebo Capsules		Gabapentin Capsules, Placebo Cream		Placebo Cream and Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/140 (5.00%)		2/144 (1.39%)		1/76 (1.32%)
Ear and labyrinth disorders
Vertigo 1	7/140 (5.00%)	7	2/144 (1.39%)	2	1/76 (1.32%)	1
1 Term from vocabulary, MedDRA 10.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: EpiCept Corporation
• Phone: 914-606-3500
• EMail: sallard@epicept.com

• Responsible Party: Stephane Allard, Chief Medical Officer, EpiCept Corporation
• ClinicalTrials.gov Identifier: NCT00475904
• Other Study ID Numbers: EPC2007-02
• First Submitted: May 17, 2007
• First Posted: May 21, 2007
• Results First Submitted: April 20, 2011
• Results First Posted: July 6, 2011
• Last Update Posted: July 27, 2011