A Study of the Efficacy and Safety of Amitriptyline/Ketamine Topical Cream in Patients With Diabetic Peripheral Neuropathy

• Sponsor: EpiCept Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00476151
• Collaborator: (none)
• Enrollment: 226
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 25

Study Details

Study Description

Brief Summary

This is a multicenter, randomized, placebo-controlled, parallel group study of EpiCept™ NP-1 Topical Cream (amitriptyline 4%/ketamine 2%) in approximately 200 patients with pain in the lower extremities due to diabetic nerve pain.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Peripheral Neuropathy; Neuralgia	Drug: EpiCept NP-1 (4% Amitriptyline/ 2% Ketamine) Topical Cream; Drug: placebo cream	Phase 2

Detailed Description

This is a phase II, multicenter, randomized, placebo-controlled, parallel group study of EpiCept™ NP-1 Topical Cream (amitriptyline 4%/ketamine 2%) in approximately 200 patients with chronic pain in the lower extremities due to diabetic peripheral neuropathy (DPN).

Study Design

• Study Type: Interventional
• Actual Enrollment: 226 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of EpiCept™ NP-1 Topical Cream in Patients With Pain From Diabetic Peripheral Neuropathy (DPN)
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo cream vehicle cream	Drug: placebo cream; inactive placebo cream applied two times daily
Active Comparator: amitriptyline 4% ketamine 2% cream active topical cream	Drug: EpiCept NP-1 (4% Amitriptyline/ 2% Ketamine) Topical Cream; topical cream applied daily for 4 weeks; Other Names: EpiCept NP-1

Outcome Measures

Primary Outcome Measures

1. Placebo vs. Active Comparison of the Change From Average Pain at Baseline to Average Pain at 4 Weeks. [baseline and 4 weeks treatment]

   diabetic peripheral neuropathy (DPN) pain is recorded on a numerical rating scale of 0 (no pain) to 10 (worst possible pain) at baseline and the endpoint of 4 weeks.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult patients with chronic pain due to diabetic peripheral neuropathy (DPN) of at least 6 months duration are eligible if they have an average daily pain score of > 4 during the baseline week.

Exclusion Criteria:

• Clinically significant intercurrent illness (e.g., endocrine, cardiac, hepatic, renal, neurologic, hematologic, skeletal) that the investigator determines could interfere with the efficacy or safety assessments in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Multiple Centers	New Delhi		India

Sponsors and Collaborators

• EpiCept Corporation

Investigators

• Principal Investigator: Robert H Dworkin, Ph.D., University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00476151
• Other Study ID Numbers: EPC2006-01
• First Posted: May 21, 2007
• Last Update Posted: May 17, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: DPN; Diabetic; Nerve Pain
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies; Ketamine; Amitriptyline

Study Results

Participant Flow

Arm/Group Title	Placebo Cream	Amitriptyline 4% Ketamine 2% Cream
Arm/Group Description	vehicle cream applied twice daily for 4 weeks	active topical cream applied twice daily for 4 weeks
Period Title: Overall Study
STARTED	112	114
COMPLETED	109	107
NOT COMPLETED	3	7

Baseline Characteristics

Arm/Group Title	Placebo Cream	Amitriptyline 4% Ketamine 2% Cream	Total
Arm/Group Description	vehicle cream applied twice daily for 4 weeks	active topical cream applied twice daily for 4 weeks	Total of all reporting groups
Overall Participants	112	114	226
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	86 76.8%	94 82.5%	180 79.6%
>=65 years	26 23.2%	20 17.5%	46 20.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.05 (11.044)	56.06 (9.350)	55.56 (10.214)
Sex: Female, Male (Count of Participants)
Female	55 49.1%	49 43%	104 46%
Male	57 50.9%	65 57%	122 54%
Region of Enrollment (participants) [Number]
India	112 100%	114 100%	226 100%

Outcome Measures

1. Primary Outcome

Title	Placebo vs. Active Comparison of the Change From Average Pain at Baseline to Average Pain at 4 Weeks.
Description	diabetic peripheral neuropathy (DPN) pain is recorded on a numerical rating scale of 0 (no pain) to 10 (worst possible pain) at baseline and the endpoint of 4 weeks.
Time Frame	baseline and 4 weeks treatment

Outcome Measure Data

Analysis Population Description

ITT (Intention To Treat) completer population, LOCF (Last Observation Carried Forward) imputation

Arm/Group Title	Placebo Cream	Amitriptyline 4% Ketamine 2% Cream
Arm/Group Description	vehicle cream applied twice daily for 4 weeks	active topical cream applied twice daily for 4 weeks
Measure Participants	108	106
Least Squares Mean (95% Confidence Interval) [units on a scale]	1.64	2.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Cream, Amitriptyline 4% Ketamine 2% Cream
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Placebo Cream		Amitriptyline 4% Ketamine 2% Cream
Arm/Group Description	vehicle cream applied twice daily for 4 weeks		active topical cream applied twice daily for 4 weeks
All Cause Mortality
	Placebo Cream		Amitriptyline 4% Ketamine 2% Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Cream		Amitriptyline 4% Ketamine 2% Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/112 (0%)		0/114 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Cream		Amitriptyline 4% Ketamine 2% Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/112 (14.3%)		17/114 (14.9%)
Blood and lymphatic system disorders
Eosiniphilia	2/112 (1.8%)	2	0/114 (0%)	0
Anemia	1/112 (0.9%)	1	0/114 (0%)	0
Eye disorders
Conjunctivitis	1/112 (0.9%)	1	0/114 (0%)	0
General disorders
Pain	1/112 (0.9%)	1	1/114 (0.9%)	1
Pyrexia	1/112 (0.9%)	1	1/114 (0.9%)	1
Edema	1/112 (0.9%)	1	0/114 (0%)	0
Infections and infestations
Rhinitis	0/112 (0%)	0	1/114 (0.9%)	1
Upper Respiratory Infection	0/112 (0%)	0	1/114 (0.9%)	1
Investigations
Aspartate aminotransferase increased	0/112 (0%)	0	4/114 (3.5%)	4
Blood lactate dehydrogenase increased	1/112 (0.9%)	1	3/114 (2.6%)	3
Blood urea increased	3/112 (2.7%)	3	1/114 (0.9%)	1
Alanine aminotransferase increased	1/112 (0.9%)	1	2/114 (1.8%)	2
Body temperature fluctuation	1/112 (0.9%)	1	0/114 (0%)	0
Electrocardiogram QT prolonged	1/112 (0.9%)	1	0/114 (0%)	0
Urine analysis abnormal	1/112 (0.9%)	1	0/114 (0%)	0
Metabolism and nutrition disorders
Hyperkalemia	1/112 (0.9%)	1	1/114 (0.9%)	1
Hypocalcemia	1/112 (0.9%)	1	0/114 (0%)	0
Hyponatremia	1/112 (0.9%)	1	0/114 (0%)	0
Nervous system disorders
Headache	0/112 (0%)	0	1/114 (0.9%)	1
Paresthesia	0/112 (0%)	0	1/114 (0.9%)	1
Somnolence	0/112 (0%)	0	1/114 (0.9%)	1
Dysesthesia	3/112 (2.7%)	3	8/114 (7%)	8
Renal and urinary disorders
Pyuria	2/112 (1.8%)	2	0/114 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	2/112 (1.8%)	2	0/114 (0%)	0
Rash	2/112 (1.8%)	2	0/114 (0%)	0
Dry skin	0/112 (0%)	0	1/114 (0.9%)	1
Skin exfoliation	0/112 (0%)	0	1/114 (0.9%)	1
Vascular disorders
Flushing	2/112 (1.8%)	2	1/114 (0.9%)	1

Limitations/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.