Evaluate the Maintenance of Effect After Long-term Treatment With Sativex® in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis
Condition: Spasticity; Multiple Sclerosis
MeSH terms: Muscle Spasticity; Multiple Sclerosis; Sclerosis
Intervention: Sativex; Placebo
Intervention description: containing delta-9-tetrahydrocannabinol (THC)(27 mg/ml):cannabidiol (CBD)(25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Dose: 100 µl oromucosal spray, as required for symptom relief; Contains no active drug and is delivered in 100 microlitre actuations by a pump action oromucosal spray
Intervention MeSH terms: Nabiximols
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Spasticity; Multiple Sclerosis

Summary:

      The purpose of this study is to evaluate the maintenance of effect after long-term treatment
      with Sativex® in subjects with symptoms of spasticity due to Multiple Sclerosis (MS) who have
      been receiving long-term benefit from treatment with Sativex®.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to give written informed consent for participation in the study.

          -  Male or female, aged 18 years or above.

          -  Subject is able (in the investigator's opinion) and willing to comply with all study
             requirements.

          -  Diagnosed with MS.

          -  Received Sativex for the relief of spasticity for at least 12 weeks prior to screening
             and willing to stop dosing with their own supply for the duration of the study.

          -  Judged to have been receiving benefit from and shown tolerability to Sativex, in the
             investigators' and subjects' opinion.

          -  Takes a minimum dose of Sativex of two sprays per day.

          -  If receiving disease-modifying medications, these must have been at a stable dose for
             at least three months prior to screening, and willing to maintain this for the
             duration of the study.

          -  Has had a stable regimen for at least 30 days prior to study entry, for all
             medications and non-pharmacological therapies that may have an affect on spasticity;
             and willing to maintain this for the duration of the study (N.B. This should be three
             months prior to study entry, in the case of Interferon therapy).

          -  Willing to allow his or her general practitioner and consultant, if appropriate, to be
             notified of participation in the study.

          -  Willing for his or her name to be notified to the responsible authorities for
             participation in this study

        Exclusion Criteria:

          -  Has any concomitant disease or disorder that has symptoms of spasticity or that may
             influence the subject's level of spasticity.

          -  Unable to rate their level of spasticity or distinguish it from other MS symptoms.

          -  Currently receiving a prohibited medication (Botulinum Toxin, or Acomplia
             (Rimonabant), and unwilling to stop or comply for the duration of the study or had
             received said medication/ therapy within three months prior to the screening visit.

          -  Unwilling to stop their own Sativex treatment for the duration of the study.

          -  Any known or suspected immediate family history of schizophrenia, other psychotic
             illness, severe personality disorder or other significant psychiatric disorder other
             than depression associated with their underlying condition.

          -  Has evidence of cardiomyopathy.

          -  Has experienced myocardial infarction or clinically relevant cardiac dysfunction
             within the last 12 months or has a cardiac disorder that, in the opinion of the
             investigator would put the subject at risk of a clinically relevant arrhythmia or
             myocardial infarction.

          -  Has a QT interval of > 450 ms (males) or > 470 ms (females) at Visit 1.

          -  Has a secondary or tertiary atrioventricular (AV) block or sinus bradycardia (HR
             <50bpm unless physiological) or sinus tachycardia (HR>110bpm) at Visit 1.

          -  Has a diastolic blood pressure of <50 mmHg or >105 mmHg (when measured in a sitting
             position at rest for five minutes) prior to randomisation

          -  Has impaired renal function e.g. creatinine clearance is lower than 50ml/min at Visit
             1 and is indicative of renal impairment.

          -  Has significantly impaired hepatic function, at Visit 1, in the investigator's
             opinion.

          -  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 any 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 has any abnormalities that, in the
             opinion of the investigator, would prevent them from safely participating in the
             study.

          -  Travel outside the UK planned during the study.

          -  Unwilling to abstain from donation of blood during the study.

          -  Subjects previously randomised into this study.