A Study to Evaluate the Efficacy of Sativex in Relieving Symptoms of Spasticity Due to Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Sativex; Placebo
Intervention description: Contains delta-9-tetrahydrocannabinol (THC) (27mg/ml): cannabidiol (CBD) (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg:CBD 60 mg) in 24 hours.; Contains peppermint oil flavouring, 0.05%(v/v); quinoline yellow,0.005% (w/v) and sunset yellow, 0.0025% (w/v) colourants, in a and ethanol:propylene glycol (50:50) excipient.
Intervention MeSH terms: Nabiximols
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 337.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to assess the efficacy of Sativex in relieving symptoms of
      spasticity in multiple sclerosis
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to give informed consent.

          -  Aged 18 years or above.

          -  Ability (in the investigator's opinion) and willingness to comply with all study
             requirements.

          -  Diagnosed with any disease subtype of multiple sclerosis of duration greater than six
             months.

          -  Diagnosed with spasticity due to multiple sclerosis of at least three months duration
             and was not wholly relieved with their current therapy.

          -  Stable dose of anti-spasticity and non-pharmacological therapies for at least 30 days
             prior to the screening visit and willingness for these to be maintained for the
             duration of the study.

          -  Stable dose of disease modifying medications for at least six months duration prior to
             the screening visit and willingness to maintain this for the duration of the study.

          -  The last six daily diary spasticity numerical rating scale scores before randomisation
             had been completed and summed to at least 24.

          -  Agreement for the responsible authorities (as applicable in individual countries),
             their primary care physician, and their consultant, if appropriate, to be notified of
             their participation in the study.

        Exclusion Criteria:

          -  Concomitant disease or disorder that had symptoms of spasticity, or that may have
             influenced the subject's level of spasticity.

          -  Received a Botulinum Toxin injection within four months prior to the screening visit
             or unwillingness to stop receiving Botulinum Toxin injections for the relief of
             spasticity for the duration of the study.

          -  Had used cannabis within 30 days of study entry and unwillingness to abstain for the
             duration for the study.

          -  Had used cannabinoid based medications within 60 days of study entry and unwillingness
             to abstain for the duration for the study.

          -  History of schizophrenia, other psychotic illness, severe personality disorder or
             other significant psychiatric disorder other than depression associated with their
             underlying condition.

          -  Known or suspected history of alcohol or substance abuse.

          -  History of epilepsy or recurrent seizures.

          -  Known or suspected hypersensitivity to cannabinoids or any of the excipients of the
             study medication.

          -  Experienced myocardial infarction or clinically relevant cardiac dysfunction within
             the last 12 months or had a cardiac disorder that, in the opinion of the investigator
             would put the subject at risk of a clinically relevant arrhythmia or myocardial
             infarction.

          -  QT interval of > 450 ms (males) or > 470 ms (females) at Visit 1.

          -  Secondary to tertiary arterial ventricular block or sinus bradycardia (heart rate < 50
             bpm) or sinus tachycardia (heart rate > 110 bpm) at Visit 1.

          -  Diastolic blood pressure of < 50 mmHg or > 105 mmHg in a sitting position at rest for
             5 minutes prior to randomisation.

          -  Impaired renal function i.e. serum creatinine clearance is lower than 50 ml/min at
             Visit 1.

          -  Significantly impaired hepatic function, at Visit 1, in the investigator's opinion
             and/or had liver function tests of equal to or greater than three times the upper
             limit of normal.

          -  Female subjects of child bearing potential and male subjects whose partner was of
             child bearing potential, unless were willing to ensure that they or their partner used
             effective contraception during the study and for three months thereafter.

          -  If female, were pregnant or lactating, or were planning pregnancy during the course of
             the study and for three months thereafter.

          -  Received an IMP within the 12 weeks before Visit 1.

          -  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 had any abnormalities that, in the
             opinion of the investigator, would prevent the subject from safely participating in
             the study.

          -  Scheduled elective surgery or other procedures, which required general anaesthesia
             during the study.

          -  Intention to donate blood during the study.

          -  Intention to travel internationally during the study.

          -  Previous randomisation into this study.