E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
postherpetic neuralgia and painful diabetic polyneuropathy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054095 |
E.1.2 | Term | Neuropathic pain |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to evaluate the safety and efficacy of lidocaine 5 medicated plaster versus pregabalin after 4 weeks of treatment in subjects with postherpetic neuralgia and diabetic polyneuropathic pain |
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E.2.2 | Secondary objectives of the trial |
To estimate the suitability of lidocaine 5 medicated plaster as stand-alone medication, as an alternative to and in combination with pregabalin. To evaluate the safety and efficacy of lidocaine 5 medicated plaster in combination with pregabalin. To evaluate the pregabalin-sparing effect of lidocaine 5 medicated plaster by down-titrating pregabalin. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Male or female subjects with major-equal 18 years of age. Written informed consent given. For women of childbearing potential, a negative urine pregnancy test. Negative urine test for drugs of abuse with the exception of short and medium acting benzodiazepine users for insomnia. Intact skin in the area of topical treatment. NRS-3 4 recalled average pain intensity during the last 3 days Creatinine clearance CLCR 30mL/min SUBJECTS WITH PAINFUL DPN Controlled, treated type 1 or 2 diabetes mellitus with glycosylated hemoglobin HbA1c minor-equal 11 . Painful, distal, symmetrical, sensomotor polyneuropathy of the lower extremities for major-equal 3 months below the knees on both extremities with at least 2 of the following symptoms present burning sensation, tingling or prickling, paresthesias, painful heat or cold sensation e.g. warm or cold water . The most painful area is coverable by up to 4 plasters. SUBJECTS WITH PHN Subjects with PHN and neuropathic pain present for major-equal 3 months after healing of the herpes zoster skin rash. Without neurolytic neurosurgical therapy for their condition. |
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E.4 | Principal 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, i.e. with a Pearl Index 1 e.g. most oral contraceptives, intra-uterine device IUD method with hormonal supplement, or male or female condom with diaphragm and a spermicidal agent foam, jelly, or cream for at least 28 days prior to enrollment, during the trial, and until 28 days after the follow-up visit. Women of childbearing age must be counseled about the use of adequate contraception 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 major-equal 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. Known to or suspected of not being able to comply with the trial protocol. Not able to communicate meaningfully with the Investigator and staff. Any dependency of the subject to the Investigator or the trial site, e.g. employees with direct involvement in the proposed trial or in other trials under the direction of this Investigator or trial site, as well as family members of the employees or the Investigator. The investigator may exclude any potential subject for any safety concern or any other reason that according to the investigator s assessment makes the patient not suitable for this trial. TRIAL-SPECIFIC Any former treatment with topical lidocaine for treatment of neuropathic pain, pregabalin, or gabapentin during the last 6 months Any concomitant use of drugs for the treatment of neuropathic pain or commonly used for the treatment of neuropathic pain e.g. Non-SSRI antidepressant drugs i.e. tricylcic antidepressants, serotonin-norepinephrine reuptake inhibitors SNRIs , e.g. venlafaxine, duloxetine . Non-steroidal anti-inflammatory drugs NSAIDs, including COX-2 inhibitors if not specifically allowed per protocol. Monoamine oxidase inhibitors MAO-inhibitors antieleptic drugs e.g. carbamazepine, clonzepam, phenytoin, valproic acid, lamotrigine, topiramate, gabapentin besides the IMPs. Benzodiazepines except for short or medium acting benzodiazepines for insomnia . Skeletal muscle relaxants. Opioids including dextromethorphan and tramadol , memantine, retinotoxins e.g. hydroxychloroquine, deferoxamine, thioridazine, vigabatrin . Known contraindications or hypersensitivity to local anesthetics of the amide type, pregabalin or paracetamol or to any of the excipients. Administration of Class I anti-arrhythmic drugs e.g. tocainide, mexiletine . Intake of other local anesthetics besides the IMPs |
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E.5 End points |
E.5.1 | Primary end point(s) |
Decrease of NRS-3 recalled average pain intensity during the last 3 days after 4 weeks of treatment with lidocaine 5 medicated plaster or pregabalin as stand alone medication, i.e. between Week 4 Visit 4 and Baseline Visit 2 , expressed as a response rate. Response is defined as a reduction of at least 2 points or a value of 4 or less on the NRS-3 scale after 4 weeks of treatment. All drop-outs will be defined as non-responders |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |