E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subject of both male and female gender affected by Secondary-Progressive (SP) or Primary-Progressive (PP) MS |
Soggetti di sesso sia maschile sia femminile affetti da SM secondaria-progressiva (SP) o primaria-progressiva (PP) |
|
E.1.1.1 | Medical condition in easily understood language |
Subject of both male and female gender affected by Secondary-Progressive (SP) or Primary-Progressive (PP) MS |
Soggetti di sesso sia maschile sia femminile affetti da SM secondaria-progressiva (SP) o primaria-progressiva (PP) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029205 |
E.1.2 | Term | Nervous system disorders |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 effect of Sativex (THC:CBD 1:1 ratio oromucosal spray) compared to placebo in modifying neurophysiological measures of spasticity (H/M ratio scores at baseline and at week 4) in patients affected by lower limbs spasticity in Progressive Multiple Sclerosis |
Valutare l’effetto di Sativex (spray oromucosale di THC:CBD in rapporto 1:1) rispetto al placebo sulla modifica di parametri neurofisologici della spasticità (H/M ratio in visita basale e week 4)nei soggetti affetti da spasticità nei arti inferiori in SM progressiva |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of Sativex compared to placebo on neurophysiological and functional measures, spasticity, pain, sleep and fatigue symptoms • To evaluate safety and tolerability of Sativex |
• Valutare l’efficacia di Sativex rispetto al placebo su misurazioni funzionali secondarie, spasticità, dolore, sonno e sintomi di affaticamento • Valutare la sicurezza e la tollerabilità di Sativex |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Aged 18 years or above Willing and able to comply with the protocol for the duration of the study Diagnosis of Secondary-Progressive or Primary-Progressive MS from at least12 months Relapse free from at least 3 months before screening visit Lower limb spasticity EDSS from >3.0 and < 6.5 Moderate to severe spasticity due to MS from at least 6 months and with stable drug treatment not able to relieve symptoms as a whole, deserving a specific add-on treatment Immunomodulatory or immunosuppressant therapies not modifed during the study and 6 months before starting the study Stable doses of anti-spasticity agents from at least 2 months prior to screening visit Have given written informed consent |
Di età uguale o superiore a 18 anni Disposti e in grado di rispettare il protocollo per tutta la durata dello studio Diagnosi di SM secondaria-progressiva o primaria-progressiva da almeno 12 mesi Senza recidive da almeno 3 mesi prima della visita di screening Spasticità degli arti inferiori EDSS da >3,0 a < 6,5 Spasticità da moderata a grave dovuta a SM da almeno 6 mesi e con trattamento farmacologico stabile generalmente non in grado di alleviare i sintomi, che necessita di uno specifico trattamento aggiuntivo Terapie immunomodulatorie o immunosoppressive non modificate durante lo studio e per i 6 mesi precedenti l’avvio dello studio Dosi stabili di farmaci antispastici da almeno 2 mesi prima della visita di screening Hanno fornito il proprio consenso informato per iscritto |
|
E.4 | Principal exclusion criteria |
Any concomitant disease that may cause spasticity or that could interfere with subject’s spasticity Botulinum Toxin injection for spasticity in the 4 months prior to screening visit Any known or suspected history of psychotic illness, alcohol or substance abuse, epilepsy, hypersensitivity to cannabinoids Significant cardiac, renal or hepatic disease Female subjects of child bearing potentials and male subjects whose partner is child bearing potential, unless willing to ensure that they or their partner use contraception during the study Female subjects who is pregnant lactating or planning pregnancy during the course of the study and for three months thereafter Sativex SmPC contraindications |
Qualsiasi patologia concomitante che potrebbe causare spasticità o che potrebbe interferire con la spasticità del paziente Iniezioni di tossina botulinica per la spasticità nei 4 mesi precedenti la visita di screening Qualsiasi anamnesi nota o sospetta di patologia psicotica, abuso di alcool o droghe, epilessia, ipersensibilità ai cannabinoidi Significativa patologia cardiaca, renale o epatica Soggetti di sesso femminile potenzialmente fertili e soggetti di sesso maschile la cui compagna è potenzialmente fertile, a meno che non siano disposti ad assicurare l’uso di contraccettivi durante lo studio Soggetti di sesso femminile in stato di gravidanza o allattamento, o che stanno pianificando una gravidanza durante il corso dello studio e per i tre mesi seguenti il suo termine Controindicazioni di Sativex SmPC |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at baseline and week 4. |
• To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at baseline and week 4. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
BASELINE VISIT 1 WEEK 4 |
VISITA BASALE VISITA 1 SETTIMANA 4 |
|
E.5.2 | Secondary end point(s) |
Neurophysiology H/M ratio: To evaluate differences in the H/M ratio scores within subjects affected by progressive MS at weeks 6 and 10 Transcranial Magnetic Stimulation Motor threshold to obtain MEPs to the upper limb (time 0-4; 6-10 weeks); MEPs amplitudes at 15% above motor threshold, measured as MEP/M ratio to APB (abductor pollicis brevis) and abductor of hallucis, in which M is the compound muscle potential in response to peripheral stimulation (time 0-4; 6-10 weeks); Intracortical facilitation/inhibition (ICI/ICF) to the upper limb (time 0-4; 6-10 weeks); Spasticity: Mean spasticity score recorded using a 0-10 11-point numerical spasticity rating scale (NRS) at baseline (pre-treatment) and week 4, 6 and 10 Mean modified Ashworth (MAS) score at baseline (pre-treatment), week 4, 6, 10 Function: Mean Timed 25 feet and 10 meters walk recorded at baseline (pre-treatment) and week 4, 6, 10 Mean Hand dexterity measured with 9-HPT recorded at baseline (pre-treatment) and week 4, 6, 10 Other MS Symptoms: Mean Sleep Quality NRS recorded at baseline (pre-treatment) and week 4, 6, 10 Pain NRS and Spasm frequency recorded at baseline (pre-treatment) and week 4, 6, 10 Fatigue measured with the Fatigue Severity Scale (FSS) recorded at baseline (pre-treatment) and week 4, 6, 10 |
Neurofisiologia • Valutare le differenze nei punteggi dell’H/M ratio nei soggetti affetti da SM progressiva alle settimane 6 e 10 Stimolazione Magnetica Transcranica • Motore, soglia di ottenere deputati per l'arto superiore (tempo 0-4, 6-10 settimane); • Ampiezze deputati del 15% al di sopra della soglia del motore, misurata come europarlamentare / M rapporto di APB (abduttore breve del pollice) e rapitore di dell'alluce, in cui M è il potenziale muscolare composto in risposta alla stimolazione periferica (tempo 0-4; 6-10 settimane ); • Intracorticale facilitazione / inibizione (ICI / ICF) per l'arto superiore (tempo 0-4, 6-10 settimane); Spasticità: • Punteggio medio spasticità registrati con un 00-10 a 11 punti numerica scala di valutazione della spasticità (NRS) al basale (pre-trattamento) e la settimana 4, 6 e 1 Significa Ashworth modificata (MAS) punteggio al basale (pre-trattamento), settimana 4, 6, 10 Funzionalità: • Tempo medio di cammino per 25 piedi e 10 metri registrato al basale (pre-trattamento) e alle settimane 4, 6, 10 • Destrezza manuale media misurata con 9-HPT (9–Hole Peg Test) registrato al basale (pre-trattamento) e alle settimane 4, 6, 10 Altri sintomi di SM: • Qualità media del sonno sulla scala NRS registrata al basale (pre-trattamento) e alle settimane 4, 6, 10 • Frequenza di dolore e spasmi sulla scala NRS registrata al basale (pre-trattamento) e alle settimane 4, 6, 10 • Spossatezza misurata per mezzo della scala FSS (Fatigue Severity Scale) registrata al basale (pre-trattamento) e alle settimane 4, 6, 10 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
BASELINE VISIT VISIT 1 WEEK 4 VISIT 2 WEEK 6 VISIT 3 WEEK 10 |
VISITA BASELINE VISITA 1, SETTIMANA 4 VISITA 2, SETTIMANA 6 VISITA 3, SETTIMANA 10 |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
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
|
Last patient out: August 2012 |
LVLS: Agosto 2012 |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |