A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years

The Efficacy, Safety and Tolerability of Sativex as an Adjunctive Treatment to Existing Anti-spasticity Medications in Children Aged 8 to 18 Years With Spasticity Due to Cerebral Palsy or Traumatic Central Nervous System Injury Who Have Not Responded Adequately to Their Existing Anti-spasticity Medications: a Parallel Group Randomised, Double-blind, Placebo-controlled Study Followed by a 24-week Open Label Extension Phase

A study to assess the effects of Sativex treatment on spasticity in a population of children and adolescents aged from 8 to 18 years with cerebral palsy or traumatic central nervous system injury. Efficacy (ability to improve symptoms), safety and tolerability will be monitored.

A 12 week randomised, double-blind, placebo-controlled,parallel group study followed by a 24-week open-label extension phase.

The primary objective is to assess the efficacy of Sativex treatment using a spasticity 0-10 numerical rating scale (NRS). The endpoint for analysis is the comparison between Sativex and placebo in the change from baseline to the end of the acute phase in mean spasticity 0-10 NRS scores (week 12 or last seven days prior to withdrawal).

The secondary objectives are to assess the safety and tolerability of Sativex via volunteered adverse events, laboratory parameters and vital signs. The efficacy of Sativex compared to placebo is also investigated for the following outcomes: spasticity (modified tardieu scale (MTS) score of the most affected limb and the modified ashworth scale (MAS) score of the main muscle groups of the upper and lower limb), sleep quality (sleep 0-10 NRS), pain (paediatric pain profile [PPP]), quality of life (of both the participant and the caregiver; cerebral palsy quality of life (QOL) questionnaire and caregiver QOL questionnaire), comfort (comfort questionnaire), depression assessment (childrens depression inventory (CDI 2)) and the caregiver's global impression of change (CGIC).

Inclusion Criteria:

• Males and females aged between 8 and 18 years suffering from cerebral palsy or traumatic central nervous system injury.
• Participant and/or authorised representative willing and able to give informed consent for participation in the study.
• To have been under treatment for their spasticity for at least one year and to have reached a stage of non-progressive spasticity.
• Participant able (in the investigators opinion) and willing to comply with all study requirements.
• Participant has received inadequate efficacy and/or experienced unacceptable side effects from previous or current treatment with at least one of the following medications for spasticity:

Baclofen, Diazepam (or another benzodiazepine), Dantrolene, Tizanidine, Gabapentin, Trihexyphenidyl.

• Gross Motor Function Classification Scale Level III - V.
• MAS of two or higher in at least one muscle group.
• Participant and/or authorised representative willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries.
• Participant and/or authorised representative willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

• Any known or suspected history of:

  • Schizophrenia or other psychotic illness, or diagnosis of schizophrenia in a first-degree relative.
  • Alcohol or substance abuse.

• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s)

• Use of cannabis or cannabinoid based medications (including within 30 days or 60 days of study entry respectively).

• Weight less than 15 kg.

• Female participants of child bearing potential and male participants 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 participant who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.

• Participants who have received an Investigational Medicinal Product (IMP) within the 12 weeks prior to the screening visit.

• Has been treated with botulinum toxin in the previous 12 weeks.

• Concomitant use of botulinum toxin

• Any other significant disease or disorder, which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, may influence the result of the study, or the participant's ability to participate in the study.

• Following a physical examination, the participant has any abnormalities that, in the opinion of the investigator would prevent the participant from safe participation in the study.

• Significant cardiac, renal or hepatic disease.

• Planned surgical procedure during the randomised phase of the study.

• Travel outside the country of residence planned during the study.

• Participants previously randomised into this study.

• Unwilling to abstain from donation of blood during the study