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 | 8.1 |
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 either postherpetic neuralgia or 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 | No |
E.3 | Principal inclusion criteria |
• Male or female subjects with ≥ 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) ≤ 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, 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 ≥ 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. Contraception with a Pearl Index < 1 is regarded as satisfactory (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]). Satisfactory contraception must have been used for at least 28 days prior to enrollment, and is to be used 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 ≥ 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 or therapies 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). • Transcutaneous electrical nerve stimulations (TENS). If concomitant medication needs to be tapered off, this taper-off must be started at Visit 1 and must be completed at Visit 2. • Known contraindications or hypersensitivity to local anesthetics of the amide type, pregabalin or paracetamol or to any of the excipients. • Intake of Class I anti-arrhythmic drugs (e.g. tocainide, mexiletine). • Administration of other local anesthetics (besides the IMPs). • Use of capsaicin in the last month prior to enrollment. • Galactose intolerance. • Lapp lactase deficiency. • Glucose-galactose malabsorption. • Evidence of another cause for pain in the area of neuropathic pain such as lumbar radiculopathy, surgery trauma, restless legs syndrome, if this could confound the assessment or self-evaluation of the neuropathic pain. • Presence of other severe pain that could confound the assessment or self-evaluation of neuropathic pain. • History of malignancy within the past 5 years (with the exception of basal cell carcinoma).
Subjects with postherpetic neuralgia • Active herpes zoster lesion or dermatitis of any origin at the affected site. • Subjects who had neurological ablation by block or neurosurgical intervention for control of their pain.
Subjects with diabetic polyneuropathy • No palpable pulse of the arteria dorsalis pedis in one foot or both feet. • Clinical signs for venous insufficiency and/or postthrombotic syndrome Stage III/IV (i.e. extensive varicosis). • Ulcers on the lower extremities. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
adaptive two-stage, stratified by indication |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | No |
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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The end of trial is defined as last subject out (LSO), meaning the date of the final follow-up visit for the last subject. Depending on the results of the interim analysis, the trial may be stopped prematurely. |
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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 |