An Observational Post-Marketing Safety Registry of Sativex®

Study Overview
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Brief Summary
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The purpose of this registry is to monitor safety outcomes of patients who are receiving Sativex® for Multiple Sclerosis (MS) spasticity and for off-label indications in the United Kingdom (UK), Germany and Sweden.

Detailed Description
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The objectives of this multi-centre, observational program are to evaluate the long-term safety of Sativex® with special regard to the following: The potential for addiction, abuse and misuse for illegal purposes The potential for long-term psychiatric effects including suicidality and psychosis The potential for mood changes / psychological effects (such as confusion / disorientation) The potential for memory impairment The effect on driving ability The potential for falls The use of MS concomitant medications All physicians who are prescribing Sativex® in the UK and those from specialist neurology centres in Germany and Sweden will be invited to participate in the registry and will be provided with information regarding the background and objectives of the study. The prescribing physician will be asked to enter the following information via electronic Case Report Forms (CRF) at 6 monthly intervals for up to 24 months for any one patient: Sativex® Use: Was Sativex® prescribed for Spasticity in MS? (Yes/No). If no, specify then indication for prescribing Sativex® Year of Spasticity diagnosis (Germany/Sweden only) Sativex® start date Sativex® daily dose (average, minimum and maximum) Date of last prescription Is Sativex® providing worthwhile benefit? (Yes/ No/ Don't Know) Has Sativex® been stopped permanently? (Yes /No). If yes, reason for stopping is to be provided. Sativex® stop date Adverse Events (AE): Have any clinically significant adverse events been reported for this patient since they started taking Sativex® (initial record); did any clinically significant adverse events occur, or were ongoing, during this period (follow-up records) (If yes, the details are recorded on an AE form) Has the patient sought medical attention because of a fall related injury; since they started taking Sativex® (initial record); during this period (follow-up records) (If yes, the details are recorded on an AE form) Has the patient experienced any suicidal thoughts or attempted suicide; since they started taking Sativex® (initial record); during this period (follow-up records) (If yes, the details are recorded on an AE form) Has the patient experienced any other significant psychiatric or psychotic events; since they started taking Sativex® (initial record); during this period (follow-up records) (If yes, the details are recorded on an AE form) Has the patient reported any change in their driving ability; since they started taking Sativex® (initial record); during this period (follow-up records) Improved No change Deteriorated Not appropriate Supporting Information: Medical History relevant to adverse events What other Spasticity medications have previously been used and are now stopped permanently (baclofen, tizanidine, benzodiazepines, gabapentin, botulinum toxin) (Germany/Sweden only) Changes to other MS symptom medications; since they started taking Sativex® (initial record); during this period (follow-up records)? Survival status: Is the patient currently alive? If no, date of death and cause of death. Was the death due to suicide (Yes/No) Paper CRF will also be available and will subsequently be entered into the electronic CRF database. The data from the Registry will be analysed descriptively and collated into summary tables and listings. A Registry report based upon the data summaries will be included within the Periodic Safety Update Reports for Sativex® and the results will be submitted to the appropriate Regulatory Agencies within 60 days of the data summaries tables and listings becoming available. Each six monthly report and the data tables and listings will be reviewed by an independent Sativex® Registry Advisory Board and a summary overview will be prepared by the committee. A final Registry report will be assembled within 180 days of the final study data being available. Any significant safety issues identified will be communicated to the relevant Regulatory Agencies immediately.

Official Title
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An Observational Post-Marketing Safety Registry Of Patients Who Have Been Prescribed Sativex®

Conditions
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Multiple Sclerosis, Diabetes, Cancer, Neuropathic Pain

Intervention / Treatment
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* Drug: Sativex®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients who are prescribed Sativex® in the UK Patients who are prescribed Sativex® from selected specialist neurology centres in Germany and Sweden.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sativex® users<br>UK: All patients and who are prescribed Sativex®. Germany and Sweden: Patients who are prescribed Sativex® from selected specialist neurology centres. | Drug: Sativex®<br>* 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.<br>* Other names: THC/CBD spray;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rates of adverse events. | The number of treatment-emergent adverse events was recorded. The incidence rate (number of patients divided by the total patient-years exposure to Sativex®) for each adverse event is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average daily number of sprays of Sativex® used. | The average daily dose of Sativex® was recorded and is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of patients experiencing fall-related injuries requiring medical attention. | Patients were asked if they had sought medical attention because of a fall-related injury; since they started taking Sativex® (initial record); during this period (follow-up records). The number of patients answering 'yes' is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of patients experiencing a change in driving ability. | Patients were asked to report any change in their driving ability; since they started taking Sativex® (initial record); during this period (follow-up records). The markers were: Improved, No change, Deteriorated, Not appropriate. The number of patients for each marker is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of patients experiencing suicidal thoughts or attempts. | Patients were asked if they had experienced any suicidal thoughts or attempted suicide; since they started taking Sativex® (initial record); during this period (follow-up records). The number of patients answering 'yes' is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of patients experiencing significant psychiatric or psychotic events other than suicidality. | Patients were asked if they had experienced any significant psychiatric or psychotic events other than suicidality; since they started taking Sativex® (initial record); during this period (follow-up records). The number of patients answering 'yes' is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Incidence of patient deaths. | The incidence of treatment-emergent deaths was recorded and the number of patient deaths is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of patients receiving worthwhile benefit from Sativex®. | Patients were asked if Sativex® was providing worthwhile benefit. The number of patients answering 'yes' at one or more time points is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of MS patients discontinuing anti-spasticity medications. | MS patients were asked what other anti-spasticity medications that have previously been used are now stopped permanently; since they started taking Sativex® (initial record); during this period (follow-up records). The number of patients for each discontinued medication is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 
| Number of MS patients discontinuing medications for MS symptoms other than anti-spasticity medications. | MS patients were asked what medications for MS symptom other than anti-spasticity medications that have previously been used are now stopped permanently; since they started taking Sativex® (initial record); during this period (follow-up records). The number of patients for each discontinued medication is presented. | Participants will be followed for the duration of Sativex treatment, an expected average of 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cannabinoids, Sativex, THC, delta-9-tetrahydrocannabinol, cannabidiol, CBD, Registry, Safety, MS