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
Overview
- Phase
- Phase 3
- Intervention
- Sativex
- Conditions
- Cerebral Palsy
- Sponsor
- Jazz Pharmaceuticals
- Enrollment
- 72
- Locations
- 14
- Primary Endpoint
- Change from baseline to the end of 12 weeks' treatment in mean spasticity 0-10 NRS score
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Eligibility Criteria
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.
Arms & Interventions
Sativex
Oromucosal spray containing delta-9-tetrahydrocannabinol (THC) (27 mg/mL):cannabidiol (CBD) (25 mg/mL). Each 100 μL spray to the sub-lingual or oral mucosa delivered THC 2.7 mg and CBD 2.5 mg. The maximum number of daily sprays was 12.
Intervention: Sativex
Placebo
Oromucosal spray containing ethanol: propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and colourings FD\&C Yellow No.5 (E102 tartrazine) (0.0260%), FD\&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD\&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD\&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%). Each 100 μL spray administered to the sub-lingual or oral mucosa delivered the colourants plus excipients. The maximum number of daily sprays was 12.
Intervention: Placebo
Outcomes
Primary Outcomes
Change from baseline to the end of 12 weeks' treatment in mean spasticity 0-10 NRS score
Time Frame: Day 0 - Day 84
The spasticity 0-10 NRS was completed daily at bedtime using a paper study diary. The difference between spasticity and spasm was clearly explained to the caregiver. The primary caregiver was asked the following question: "This question is about your child's muscles and how soft or tight/hard they have felt today. Think carefully about how your child's muscles have felt today and circle a number from 0 to 10 that best describes this, where: 0 = 'my child's muscles have felt totally relaxed' and 10 = 'my child's muscles have felt the tightest/hardest they have ever felt'". A reduction in score indicates an improvement in condition. The mean spasticity 0-10 NRS score of the last 7 days of the baseline period was used for a patient's mean baseline score. The mean 0-10 NRS score of the last 7 days prior to completion/withdrawal was used for a patient's mean end of treatment score.
Secondary Outcomes
- Change from baseline to the end of 12 weeks' treatment in mean MTS score of the most affected limb(Day 0 - Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean sleep quality 0-10 NRS score(Day 0 - Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean comfort questionnaire outcome (time spent sitting in comfort)(Day 0 - Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean caregiver QOL (SF-36-II) score(Day 0 - Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean CDI 2 score(Day 0 - Day 84)
- CGIC response on participants ease of transfer at the end of 12 weeks' treatment(Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean MAS score of the main muscle groups of the upper and lower limb(Day 0 - Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean Paediatric Pain Profile (PPP) score(Day 0 - Day 84)
- Change from baseline to the end of 12 weeks' treatment in mean cerebral palsy QOL score(Day 0 - Day 84)
- CGIC response on participants general functional capabilities at the end of 12 weeks' treatment(Day 84)
- The incidence of adverse events during the randomised treatment period(Day 0 - Day 84)