A Randomized Study of Sativex on Cognitive Function and Mood: Multiple Sclerosis Patients

Phase 4

Completed

Conditions: Spasticity
Multiple Sclerosis

Interventions: Drug: Placebo
Drug: Sativex

Registration Number: NCT01964547

Lead Sponsor: Jazz Pharmaceuticals

Brief Summary: A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.

Detailed Description: Eligible patients entered this 50 week multicenter, double-blind, randomised, placebo-controlled, parallel group study which evaluated the effect of Sativex on cognitive performance. At each scheduled clinic visit, patients were assessed for cognitive performance, mood, severity of spasticity, use of investigational medicinal products and number of visits to a healthcare professional. Primary efficacy comparisons were made between scores recorded during baseline and scores recorded at the end of treatment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 121

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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%). Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability.
Sativex	Sativex	Contains 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. Each actuation delivers THC 2.7 mg and CBD 2.5 mg. Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to the End of Treatment in Paced Auditory Serial Addition Test (PASAT) Total Score.	0-48 weeks	The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Stimulus presentation rates were adapted for use with multiple sclerosis patients. The PASAT is presented on audio compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds (PASAT 1) or every 2 seconds (PASAT 2), and the patient must add each new digit to the one immediately prior to it. The test score is the sum of the total number of correct sums given (out of 60 possible) in each trial. An increase in score indicates an improvement in condition.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to the End of Treatment in Beck Depression Inventory-II (BDI-II) Total Score.	0-48 weeks	The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For patients eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A reduction in score indicates an improvement in condition.
Caregiver's Global Impression of Change (CGIC) in the Severity of the Patient's Spasticity at the End of Treatment.	0-48 weeks	Caregivers were asked the following question to be rated on a seven-point scale: "How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The number of patients for each of the markers is presented at the final study visit.
Physician's Global Impression of Change (PGIC) in the Severity of the Patient's Spasticity at the End of Treatment.	0-48 weeks	Physicians were asked the following question to be rated on a seven-point scale: "How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better. The number of patients for each of the markers is presented at the final study visit.
Change From Baseline to End of Treatment in Modified Ashworth Scale Total Score.	0-48 weeks	All 20 muscle groups were assessed for spasticity (using a 0-5 scale): 0= 'no increase in muscle tone' to 5= 'affected part(s) rigid in flexion or extension'. The score for all 20 muscle groups were added to give a total score out of 100. A decrease in score indicates an improvement in condition.
Change From Baseline to End of Treatment in Number of Visits to a Healthcare Professional.	0-48 weeks	At baseline, patients were asked how many times they had visited a healthcare professional in the previous 12 weeks. At subsequent visits, patients were asked how many times they had visited a healthcare professional since their last study visit. The change from baseline to the end of treatment is presented. A decrease in number indicates an improvement in condition.
The Number of Patients With a Treatment-emergent Flag Using the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Course of the Study.	0-48 weeks	Patients were scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags were as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of patients with a treatment-emergent flag is presented.
Incidence of Adverse Events as a Measure of Patient Safety.	0-50 weeks	The number of subjects who experienced an adverse event during the course of the study is presented.
Subject Global Impression of Change (SGIC) in the Severity of Their Spasticity at the End of Treatment.	0-48 weeks	Patients were asked the following question, to be rated on a seven-point scale: "Please assess the change in your spasticity since immediately before receiving the first dose of study treatment (Visit 1) using the scale below". The markers were: 'Very much worse', 'Much worse', 'Minimally worse', 'No change', 'Minimally better', 'Much better' or 'Very much better'. The number of patients for each of the markers is presented at the final study visit.
Change From Baseline to End of Treatment in Timed 10-meter Walk Times.	0-48 weeks	Only those patients for whom it was appropriate (i.e. ambulatory patients) were timed for how long it took to walk 10 metres. If a patient started the 10-meter walk but was unable to complete it, an estimated time for completion was calculated based on the available data. A negative difference from baseline indicates an improvement in condition.