Efficacy and Safety of Topical Versus Systemic Treatment in Postherpetic Neuralgia and Diabetic Polyneuropathic Pain

Safety and Efficacy of Lidocaine 5% Medicated Plaster in Comparison to Systemic Treatment in Postherpetic Neuralgia and Diabetic Polyneuropathic Pain.

The purpose of this study is to evaluate lidocaine as topical treatment for peripheral neuropathic pain (as stand-alone treatment and in combination with systemic treatment)

Study Overview

• Status: Completed
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Topical analgesic; Drug: Topical analgesic; Drug: oral intake

• Study Type: Interventional
• Enrollment (Actual): 431
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects with >= 18 years of age
• Intact skin in the area of topical treatment
• Creatinine clearance CLCR >= 30 mL/min
• NRS-3 > 4 (recalled average pain intensity during the last 3 days)

Subjects with DPN

• Controlled, treated type 1 or 2 diabetes mellitus with glycosylated hemoglobin (Hba1c)<= 11%
• Painful, distal symmetrical, sensomotor polyneuropathy of the lower extremities for >= 3 months (below the knees on both extremities) with at least 2 of the following symptoms present: burning, sensation, tingling or prickling, numbness from time to time, painful heat or cold sensation (e.g. warm or cold water)

Subjects with PHN

• Subjects with PHN and neuropathic pain present for >= 3 months after healing of the herpes zoster skin rash.
• Without neurolytic neurosurgical therapy for their condition.

Exclusion Criteria:

General

• Evidence or history of alcohol, medication or drug abuse and/or dependency in the past 2 years, unstable psychological personality requiring intermittent or permanent treatment.
• Psychiatric illness (subjects with well-controlled depression or anxiety disorder may participate if they are not taking any of the prohibited medications defined (below), epilepsy or suicide risk.
• Pregnant or breastfeeding women
• Women of childbearing potential who are sexually active without satisfactory contraception for at least 28 days prior to enrollment, during the trial, and until 28 days after the follow-up visit.
• Subjects with severe cardiac impairment e.g. NYHA class > 3, myocardial infarction less than 6 months prior to enrollment, and/or unstable angina pectoris.
• Subjects with severe hepatic disorder and/or AST or ALT >= 3x the upper limit of normal.
• Subjects with known or suspected severe renal failure (CLCR < 30 mL/min).
• Anticipated need for surgery during the trial, requiring at least regional or general anesthesia.
• Subjects who are undergoing active treatment for cancer, are known to be infected with HIV or being acutely and intensively immunosuppressed following transplantation.
• Participation in another trial of investigational medicinal products or devices parallel to or less than 1 month before entry into the trial, or previous participation in this trial.

Trial specific:

• Any concomitant use of drugs for the treatment of neuropathic pain or commonly used for the treatment of neuropathic pain.
• Use of transcutaneous electrical nerve stimulations (TENS) after enrollment.
• CLCR < 30 mL/min
• Evidence of another cause for pain in the area of neuropathic pain such as lumbar radiculopathy, surgery trauma, restless legs syndrome, if this coud confound the assessment or self-evaluation of the neuropathic pain.
• Presence of other severe pain that could confound the assessment or self-evaluation of the neuropathic pain.
• History of malignancy within the past 5 years (with the exception of basal cell carcinoma).

Subjects with PHN

• Active herpes zoster lesion or dermatitis of any origin at the affected site with PHN.
• Subjects who had neurological ablation by block or neurosurgical intervention for control of pain in PHN.

Subjects with DPN

• No palpable pulse of the arteria dorsalis pedis in both feet.
• Clinical signs for venous insufficiency and/or postthrombotic syndrome Sage III/IV (i.e. extensive varicoses)
• Ulcers on the lower extremities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Topical analgesic; max. 3 plasters per day for PHN patients max. 4 plasters per day for DPN patients; Drug: Topical analgesic; 3 plasters for PHN patients per day 4 plasters for DPN patients per day
Active Comparator: 2	Drug: oral intake; 300 to 600 mg per day taken orally
Experimental: 3	Drug: Topical analgesic; max. 3 plasters per day for PHN patients max. 4 plasters per day for DPN patients; Drug: Topical analgesic; 3 plasters for PHN patients per day 4 plasters for DPN patients per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction of pain expressed by response rate after 4 weeks treatment every 4 weeks of single or combination treatment: change in neuropathic pain, change in quality of life, change in sleep quality	4 weeks

Collaborators and Investigators

• Sponsor: Grünenthal GmbH
• Investigators: Principal Investigator: Ralf Baron, Prof. Dr., Klinik für Neurologie, Christian-Albrechts-Universität Kiel, Schittenhelmstr. 10, 24105 Kiel, Germany

Publications and helpful links

General Publications

• Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study. Curr Med Res Opin. 2009 Jul;25(7):1663-76. doi: 10.1185/03007990903047880.
• Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin. 2009 Jul;25(7):1677-87. doi: 10.1185/03007990903048078.
• Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. Efficacy and safety of 5% lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: interim analysis from an open-label, two-stage adaptive, randomized, controlled trial. Clin Drug Investig. 2009;29(4):231-41. doi: 10.2165/00044011-200929040-00002.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: December 20, 2006
• First Submitted That Met QC Criteria: December 20, 2006
• First Posted (Estimate): December 21, 2006

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: October 7, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Multiple dose; Topical analgesic
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Neuralgia, Postherpetic; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics
• Other Study ID Numbers: 796838; KF10004/03 (Other Identifier: Sponsor study number)