E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Spasticity in multiple sclerosis (MS). |
|
E.1.1.1 | Medical condition in easily understood language |
Spasticity in multiple sclerosis (MS). |
|
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 | LLT |
E.1.2 | Classification code | 10041416 |
E.1.2 | Term | Spasticity |
E.1.2 | System Organ Class | 100000004852 |
|
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 compare the change in cognitive performance and psychological
status of patients with spasticity due to MS when treated with Sativex
or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of Sativex on mood and spasticity To assess the safety and tolerability of Sativex. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion: Subjects meeting the following criteria will be considered eligible for this study.
• Subject is aged 18 years or above.
• Diagnosed with any disease sub-type of MS.
• Diagnosed with symptomatic spasticity due to MS.
• Subject has at least moderate spasticity in the opinion of the
investigator.
• Subject fulfils at least one of the two criteria below. Subject must
be either:
• Currently established on a regular dose of anti-spasticity therapy, or
• Previously tried and failed anti-spasticity therapy.
• Stable medication regimen for at least 4 weeks prior to study entry,
for all medications which may have an effect on spasticity and/or
cognition.
• If the subject is taking disease modifying medication this must be at
a stable dose for 3 months prior to initial visit.
• Willing and able to give informed consent.
• Willing and able to comply with all study requirements.
• Willing for his or her name to be notified to the responsible
authorities for participation in this study, as applicable.
• Willing to allow his or her primary care practitioner and consultant,
if appropriate, to be notified of participation in the study. |
|
E.4 | Principal exclusion criteria |
Exclusion: The subject may not enter the study if ANY of the following
apply:
• Any history or immediate family of schizophrenia, other psychotic
illness, severe personality disorder or other significant psychiatric
disorder other than depression associated with their underlying
condition.
• Any concomitant disease or disorder (such as poorly controlled
epilepsy or seizures) that may influence the subject’s level of
cognition or mood.
• Currently using or has used cannabis or cannabinoid-based
medications within 30 days of study entry and unwilling to abstain for the duration of the study.
• Any known or suspected history of a diagnosed dependence
disorder, current heavy alcohol consumption (more than 60g of pure alcohol per day [equivalent to a bottle of wine (0.75l) or five glasses of lager (1.5l) or four double liquors] for men, and more than 40g of pure alcohol per day [equivalent of two-thirds of that stated for men] for women), current use of an illicit drug or current non-prescribed use of any prescription drug.
• Any known or suspected hypersensitivity to cannabinoids or any of
the excipients of the Investigational Medicinal Product (IMP)(s).
• Female subjects of child bearing potential and male subjects whose
partner is of child bearing potential, unless willing to ensure that
they or their partner use effective contraception during the study
and for three months thereafter.
• Female subject who is pregnant, lactating or planning pregnancy
during the course of the study and for three months thereafter.
• Subjects who have received an IMP within the 12 weeks prior to
the initial visit.
• Any other significant disease or disorder which, in the opinion of
the investigator, may either put the subject at risk because of
participation in the study, may influence the result of the study, or
the subject’s ability to participate in the study.
• Following a physical examination, the subject has any
abnormalities that, in the opinion of the investigator would prevent
the subject from safe participation in the study.
• Subjects previously randomised into this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in cognitive function as assessed by the total Paced Auditory Serial Addition Test (PASAT I and II) score
from baseline (Visit 1) to end of treatment visit (Visit 5 Day 337 or
withdrawal date). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To evaluate the efficacy of Sativex compared with placebo on:
• Mood as assessed by the BDI-II2
• Subject Global Impression of Change in severity of spasticity
• Caregiver Global Impression of Change in severity of spasticity
• Physician Global Impression of Change in severity of spasticity
• Modified Ashworth Scale score
• Timed 10-metre walk
To assess the safety and tolerability of Sativex:
• Adverse Events
• Clinical Laboratory Tests
• Vital signs
• Suicidal tendencies as assessed by the Colombia-Suicide Severity Rating Scale (C-SSRS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All end points will be evaluated on visits 1,2,3,4 & 5 apart from the following:
• Clinical Laboratory tests will be evaluated at visit 1, 3 and 5 only.
• Adverse Events will be evaluated at all visits (1-6)
• Number of Visits to a Healthcare Professional
• Suicidal Tendencies as Assessed by the Columbia-Suicide Severity Rating Scale |
|
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 6 |
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
|
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |