E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diabetic peripheral neuropathy |
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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 | 10012683 |
E.1.2 | Term | Diabetic peripheral neuropathy |
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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 first study objective is to define the dose-response relationship of F13640 compared to a placebo with respect to analgesic efficacy and safety in patients with moderate to severe painful peripheral diabetic polyneuropathy. |
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E.2.2 | Secondary objectives of the trial |
The second objectives are the evaluation of potential rebound effect, addiction effect and remanent dose effect after study treatment discontinuation. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Outpatient, man or woman, 18 to 65 years old - Woman of childbearing potential must have been using an effective method of contraception, as assessed by the investigator, for at least 2 months before selection in the study, and must accept to go on using it during the whole duration of the study and up to 1 month after the last dose of the study treatment, in order to avoid pregnancy while being exposed to the study treatment A pregnancy test will be carried out at selection visit, at randomisation visit and at the last study visit of the patient. - Moderate to severe painful peripheral diabetic polyneuropathy with the 4 following characteristics: Diagnosis based on clinical examination, and appropriate assessment of patient’s signs and symptoms (clinical portion of Michigan Neuropathy Screening Instrument score ≥ 3) Following diabetes mellitus type 1 or 2, diagnosed for at least 3 years with stable glycaemic assessment for at least 3 months Haemoglobin A1c (HbA1c) level <10 % at selection Pain persisting for more than 3 months - Average 24-hour recall pain intensity score > 40 and < 90 on a 0-100 Visual Analogue Scale (VAS) at selection visit - Average 24-hour recall pain intensity score in the PED > 40 on a 0-100 unit VAS, over the week preceding randomisation visit (at least 4 assessable days)
-Affiliated to a social security system, or is a beneficiary, if applicable in the national regulation -Patient having signed his/her written informed consent -Patient able and willing to use the PED device daily for the duration of the study; able to hear and respond to the PED audible prompts, able to read and understand the text in local language on the PED screen
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E.4 | Principal exclusion criteria |
- Any clinically significant hepatic, renal, gastro-intestinal, endocrinal (excluding diabetes mellitus), cardiovascular, neurological, psychiatric or haematological or current disease unrelated to the cause of pain, which may interfere with pain evaluation, patient safety and the course of the study in the investigator’s opinion - Current major depressive disorder requiring a pharmacological treatment - Severe nephropathy (creatinin clearance < 50 ml/min) - Presence of significant nociceptive, inflammatory or central neuropathic pain - Presence of vascular chronic pain, with particular regard for severe diabetic arteriopathy of the lower limbs characterised by the presence of ulceration and/or necrosis - Phantom pain - Complex Regional Pain Syndrome - Physical techniques, surgery and psychological support that can modulate the perception of pain (except if maintained stable during the trial when unavoidable - AST/SGOT and ALT/SGPT greater than 2 time the upper normal values - Blood creatinine value > 150 μmol/L - Albuminuria/creatininuria > 300 mg/g - SBP < 120 mm Hg (at selection and randomisation, in supine position, and after a 10 min-rest) - ECG: QTc > 450 ms - History of alcohol or narcotic drug dependence in the 2 years preceding the selection or alcohol or narcotic abuse in the 6 months preceding the selection - Known hyper-reactivity or hyper-sensitivity to 5-HT agonists - Intake of any prohibited treatments which cannot be stopped - For patient having been treated by prohibited treatments, no respect of a wash-out period of at least 5 T1/2 of the treatment prior to randomisation - Woman pregnant or in the post-partum period (at least 6 months) or is a nursing mother - Woman sterile or in post-menopause state (12 month-amenorrhoea) impossible to document - Is a family member or work associate (secretary, nurse, technician,…) of the Investigator - Mentally unable to understand the nature, objectives and possible consequences of the trial; or refusing to subject himself / herself to its constraints - Has participated in another clinical trial within the last 3 month(s), has received treatment with known remanant effects or undergone investigation liable to interfere with the present clinical trial - Has forfeited his / her freedom by administrative or legal award or is under guardianship
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E.5 End points |
E.5.1 | Primary end point(s) |
Response to treatment defined as a decrease of at least 30% on the weekly average 24-hour recall pain intensity score on a 0-100 Visual Analogue Scale (VAS), between the baseline (the last week before the first study drug intake, scheduled on D1) and the last week before the end of fixed dose period (D56 or End of Fixed Dose visit –EFD-). Patients who discontinued prematurely fixed dose for insufficient response and/or worsening will be classified as non-responders. For patients having taken rescue medication and for patients who take non-allowed concomitant treatment during the last week before the end of fixed dose period, Validation Committee will decide whether he (she) is a responder or not. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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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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 | 4 |
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 | 4 |