E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Central neuropathic pain due to spinal cord injury, based on clinical history, clinical examination and appropriate assessment of patient’s signs and symptoms, according to the International Association for the Study of Pain (IASP) definition |
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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 | 10064012 |
E.1.2 | Term | Central pain syndrome |
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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 |
To evaluate the efficacy of F13640 in spinal cord injury patients with moderate to severe central neuropathic pain, when administered for 12 weeks including a 7-day titration period. |
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E.2.2 | Secondary objectives of the trial |
To evaluate pain relief, impact on sleep, mood and motricity, safety and tolerability of F13640 in spinal cord injury patients with moderate to severe central neuropathic pain, when administered for 12 weeks including a 7-day titration period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Out patient or institutionalised patient, male or female- Aged > or = 18 years and < or = 65 years - Diagnosis of spinal cord injury (post-traumatic, post-ischemic, non progressive myelitis, syringomylia…) for at least 1 year with stable neurological lesions for at least 6 months before the selection - Diagnosis of central neuropathic pain due to spinal cord injury, based on clinical history, clinical examination and appropriate assessment of patient’s signs and symptoms, according to the International Association for the Study of Pain (IASP) definition - Pain having persisted continuously for at least 6 months before the selection - 24-hour recall pain intensity score ≥ 4 and < or = 9 on a 11-point paper numerical rating scale at selection visit - Record of at least 4 assessable evaluations of the 24-hour recall pain intensity score in the PDA over the 7 days preceding the randomization - Average 24-hour recall pain intensity score of the last 7 days ≥ 4 on a 11-point numerical rating scale (NRS on PDA) before randomization visit- DN4 score ≥ 4 at selection - AST/SGOT and ALT/SGPT less than 2 times the upper normal values at the selection - Creatinine clearance > 60 ml/mn - QTc less than the upper limit of the normal range at the selection - For the other laboratory safety tests and ECG parameters, normal or considered as not clinically significant, in the investigator’s opinion - Patient having given his/her written informed consent or his/her oral informed consent attested by a witness independent of the investigator and the sponsor, in case of motor function impairement in the arms - Patients affiliated to a social security system, or is a workers beneficiary (if applicable in the national regulation) - Patient able to read and understand the text on the PDA screen, able to hear the audible prompts, and able to use a PDA device daily for the whole duration of the study. If the patient is physically unable to use the PDA or to complete self-reporting questionnaires or scales, he/she should be assisted by identified caregivers. |
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E.4 | Principal exclusion criteria |
- All conditions that can interfere with the pain assessment: presence of pain of other origin (nociceptive, inflammatory or peripheral neuropathic pain component) that could confound the assessment of central neuropathic pain related to SCI (for example if the intensity of pain of other origin is higher than the intensity of the neuropathic pain or if the patients are unable to distinguish between neuropathic pain and pain of other origin) - Demyelinating disease (multiple sclerosis…) - Complex Regional Pain Syndrome and other above level neuropathic pain - Pain related to complete cauda equina lesions - Refractory neuropathic pain (no response to more than 3 therapeutic classes well conducted, previously taken for central neuropathic pain) - Significant cognitive impairment on the investigator’s opinion - Severe dysautonomic tension instability - Uncontrolled arterial hypertension (SBP >140 mm Hg and/or DBP > 90 mm Hg) - Major depression requiring a pharmacological treatment - Diabetes mellitus - Any clinically significant hepatic, renal, respiratory, gastro-intestinal, cardiovascular, autoimmune, hematological, neurological or psychiatric history or current disease unrelated to the cause of neuropathic pain which may interfere with pain evaluation and the course of the study on the investigator’s opinion - History of alcohol or narcotic abuse within the 6 months preceding the selection or alcohol or narcotic dependence within the 2 years preceding the selection - Pregnancy or breast-feeding - Woman of childbearing potential who is unwilling or unable to use a medically accepted and well documented method of contraception (chirurgical or hormonal birth control or intrauterine device only) during 2 months before the inclusion in the study, 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 the selection visit, on D1 before initiation of the treatment, after the last administration of study treatment on D84 (or PW) and at the end of study visit Man able to father a child unwilling or unable to practice an effective mean of birth control while participating in this study and up to one month after the last dose of the study treatment - Intake of any unauthorized treatment which cannot be stopped - For patients having been treated by a prohibited treatment, a wash-out period of at least 5 T1/2 of the treatment must be respected prior to inclusion on D1- Patient with previous history of pharmacological sensitivity or hypersensitivity to 5-HT agonists - History of drug allergy or current allergic reaction - Patient in the exclusion period of a previous study (at least 5 T1/2 of the previous investigational product) - Patient involved in any other biomedical research during the study - Patient who could not be contacted in case of emergency - 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 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) |
The primary criterion is the response to treatment defined as an average decrease from baseline, i.e. the last week before inclusion, of at least 30% on the 24-hour recall pain intensity score recorded on a Numeric Rating Scale by electronic diary within the last week before the end of treatment (D84 or premature withdrawal for any reason other than lack of efficacy); patients in whom the average daily dose of the intake of rescue medication during the last week before the end of treatment has increased by 15% or more compared to the last week before inclusion, will be considered 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 | Yes |
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) | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |