E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Peripheral neuropathic pain in subjects with carpal tunnel syndrome |
Dolore neuropatico periferico in soggetti con sindrome del tunnel carpale |
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E.1.1.1 | Medical condition in easily understood language |
Peripheral neuropathic pain in subjects with carpal tunnel syndrome |
Dolore neuropatico periferico in soggetti con sindrome del tunnel carpale |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007698 |
E.1.2 | Term | Carpel tunnel syndrome |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077974 |
E.1.2 | Term | Peripheral neuropathic pain |
E.1.2 | System Organ Class | 100000004852 |
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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 assess the efficacy and safety of two successive intradermal administrations of several injections of BoNT-A versus placebo, administered 12 weeks apart, in subjects with CTS and NP. |
Valutare l'efficacia e la sicurezza di due successive somministrazioni intradermiche di diverse iniezioni di BoNT-A rispetto al placebo, somministrate a distanza di 12 settimane, in soggetti con CTS e NP. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study include: a) Assessment of the therapeutic gain of BoNT-A in terms of relief of spontaneous pain; b) Assessment of BoNT-A effects in reducing neuropathic symptoms; c) Assessment of BoNT-A impact on patient’s quality of life; d) Assessment of BoNT-A safety and tolerability. |
Gli obiettivi secondari di questo studio includono: a) Valutazione del guadagno terapeutico di BoNT-A in termini di sollievo dal dolore spontaneo; b) Valutazione degli effetti di BoNT-A nella riduzione dei sintomi neuropatici; c) Valutazione dell'impatto di BoNT-A sulla qualità della vita del paziente; d) Valutazione della sicurezza e tollerabilità di BoNT-A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A participant will be eligible to enroll in the study only if all the following criteria are met: a) The participant is a male or female subject aged =18 and =60 years old; b) The participant meets the criteria for probable or definite NP according to the International Association for the Study of Pain [Treede 2008]; c) The participant has been having daily pain, attributable to CTS, for at least 6 months; d) The pain level is rated as moderate–severe (4–8 points) according to the 11-point NRS; e) The participant is able and willing to provide written informed consent; f) We allow the concomitant use of analgesic treatments if they have been used at a stable doses for 4 weeks before the enrolment and for the whole study. |
Criteri di inclusione: a) Soggetto maschio o femmina di età =18 anni e =60 anni; b) NP probabile o definitiva secondo i criteri dell'International Association for the Study of Pain; c) Dolore quotidiano attribuibile a CTS per almeno 6 mesi; d) Dolore moderato-severo secondo la scala di valutazione numerica a 11 punti (NRS; 4-8); e) è consentito l'uso concomitante di trattamenti analgesici se sono stati utilizzati a dosi stabili per 4 settimane prima dell'arruolamento e per l'intero studio; f) Firma del consenso informato firmato prima della partecipazione allo studio. |
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E.4 | Principal exclusion criteria |
A patient will be ineligible for enrolment in this study if any of the following criteria are met: 1) The pain level is rated as =9 on the 11-point NRS; 2) The participant has CTS with atrophy of median-innervated muscles; 3) The participant presents contraindications or hypersensitivity to BoNT-A; 4) The participant suffers from disorders of the neuromuscular junction, coagulation disorders, or major psychiatric disorders; 5) The participant is using drugs acting on neuromuscular junctions, topical drugs (e.g., capsaicin or lidocaine), or anesthetic blocks; 6) The participant has diabetes, rheumatoid arthritis, connective tissue diseases, vasculitis, untreated hypothyroidism, acromegaly. 7) The participant has previously used BoNT-A; 8) The participant is pregnant or breastfeeding; 9) The participant is enrolled in another interventional trial for the treatment of the same disease. |
Criteri di esclusione: 1) Livello di dolore =9 su NRS a 11 punti; 2) STC con atrofia dei muscoli innervati mediani; 3) Soggetti con controindicazioni o ipersensibilità a BoNT-A; 4) Soggetti con disturbi della giunzione neuromuscolare, disturbi della coagulazione o disturbi psichiatrici maggiori; 5) Soggetti con diabete, artrite reumatoide, malattie del tessuto connettivo, vasculite, ipotiroidismo non trattato, acromegalia; 6) Soggetti che utilizzano farmaci che agiscono sulle giunzioni neuromuscolari, farmaci topici (es. capsaicina o lidocaina) o anestetici; 7) Utilizzo precedente di BoNT-A; 8) Donne in gravidanza o che allattano; 9) Soggetti arruolati in un altro studio interventistico per il trattamento della NP. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the efficacy of two successive administrations of several injections of BoNT-A, compared with placebo, measured as: 1) Change in mean weekly self-reported average daily pain intensity (mean pain over the past 24 hours recorded every morning in patient’s diary during a week) measured by the 11-point numerical rating scale (NRS, 0=no pain, 10=maximum pain imaginable) of the brief pain inventory (BPI) from baseline (one week before randomisation) to 24 weeks after the first administration. 2) Change in weekly self-reported maximum daily pain intensity (maximum pain intensity over the past 24 hours recorded every morning in patient’s diary) measured by the 11-point NRS of the BPI from baseline (1 week before randomisation) to 24 weeks after the first administration. Patients with a reduction > 30% in pain intensity as compared to baseline are considered responders. That is, we expected a movement of 2 points on NRS scale to be of clinical significance |
L'endpoint primario di efficacia è l'efficacia di due somministrazioni successive di diverse iniezioni di BoNT-A, rispetto al placebo, misurata come: 1) Variazione dell'intensità media giornaliera media settimanale del dolore auto-riferita (dolore medio nelle ultime 24 ore registrato ogni mattina nel diario del paziente durante una settimana) misurato dalla scala di valutazione numerica a 11 punti (NRS, 0=nessun dolore, 10=massimo dolore immaginabile) dell'inventario breve del dolore (BPI) dal basale (una settimana prima della randomizzazione) a 24 settimane dopo la prima amministrazione. 2) • Variazione dell'intensità del dolore giornaliera massima auto-riferita settimanalmente (intensità massima del dolore nelle ultime 24 ore registrata ogni mattina nel diario del paziente) misurata dal NRS a 11 punti del BPI dal basale (1 settimana prima della randomizzazione) a 24 settimane dopo la prima amministrazione. I pazienti con una riduzione > 30% dell'intensità del dolore rispetto al basale sono considerati responder. Cioè, ci aspettavamo che un movimento di 2 punti sulla scala NRS fosse di significato clinico |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Therapeutic gain of the second administration of BoNT-A, in terms of relief of spontaneous pain, measured as change in mean weekly average daily pain intensity measured by the 11-point NRS of the BPI from one week before 12 weeks and 24 weeks and change in maximum pain from 12 weeks and 24 weeks, in subjects who received two administrations. 2) Effects of BoNT-A on: a) severity of brush-induced allodynia measured on the Visual Analogue Scale (VAS) from baseline to 24 weeks; b) sensory disturbances and hyperalgesia in response to mechanical punctate and thermal stimuli measured by sensory assessment at the bed side from baseline to 24 weeks; c) Neuropathic symptoms (ie, burning pain, deep pain, paroxysmal pain, paraesthesia or dysaesthesia, and allodynia) measured with the Neuropathic Pain Symptom Inventory (NPSI) from baseline to 24 weeks.Impact of BoNT-A treatment on patient’s quality of life measured through the Visual Analogue Scale (VAS) of the EuroQoL EQ-5D-5L from 0 (imaginable health state) to 100 (worst imaginable health state) from baseline to 24 weeks. 3) Safety and tolerability of botulinum toxin treatment are assessed throughout the study period using neurologic examination and a systematic and planned methodology including serious adverse events (SAE), treatment- emergent AEs (TEAEs) and AEs leading to withdrawal. |
Endpoint secondario di efficacia: 1) Guadagno terapeutico della seconda somministrazione di BoNT-A, in termini di sollievo dal dolore spontaneo, misurato come variazione dell'intensità media settimanale media giornaliera del dolore misurata dall'NRS a 11 punti del BPI da una settimana prima di 12 settimane e 24 settimane e variazione del dolore massimo da 12 settimane e 24 settimane, in soggetti che hanno ricevuto due somministrazioni. 2) Effetti di BoNT-A su: a) gravità dell'allodinia indotta dal pennello misurata sulla Visual Analogue Scale (VAS) dal basale a 24 settimane; b) disturbi sensoriali e iperalgesia in risposta a stimoli meccanici puntati e termici misurati mediante valutazione sensoriale al letto dal basale a 24 settimane; c) Sintomi neuropatici (ossia, dolore bruciante, dolore profondo, dolore parossistico, parestesia o disestesia e allodinia) misurati con l'Inventario dei sintomi del dolore neuropatico (NPSI) dal basale a 24 settimane. Impatto del trattamento con BoNT-A sulla qualità della vita del paziente misurato attraverso la scala analogica visiva (VAS) dell'EuroQoL EQ-5D-5L da 0 (stato di salute immaginabile) a 100 (stato di salute peggiore immaginabile) dal basale a 24 settimane. 3) La sicurezza e la tollerabilità del trattamento con tossina botulinica sono valutate durante tutto il periodo di studio utilizzando un esame neurologico e una metodologia sistematica e pianificata che include eventi avversi gravi (SAE), AE emergenti dal trattamento (TEAE) e AE che portano alla sospensione. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |