A Study to Evaluate the Efficacy of Sativex in Relieving Symptoms of Spasticity Due to Multiple Sclerosis

NCT ID: NCT01599234

Last Updated: 2023-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 337 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2005-12-31

Brief Summary

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

Detailed Description

This was a 15 week (one week baseline and fourteen weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex in subjects with symptoms of spasticity due to multiple sclerosis. Eligible subjects entered a seven day baseline period. Subjects then returned to the centre for randomisation and dose introduction. Visits occurred at the end of treatment weeks two, six, ten and at the end of the study (treatment week 14) or earlier if they withdrew.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sativex

Active treatment

Group Type: EXPERIMENTAL

Sativex

Intervention Type: DRUG

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.

Placebo

Control

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Sativex

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.

Intervention Type: DRUG

Placebo

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 Type: DRUG

Other Intervention Names

GW-1000-02

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine Collin

Role: PRINCIPAL_INVESTIGATOR

The Royal Berkshire and Battle Hospitals NHS Trust, London Road, Reading, Berkshire, RG1 5AN.

Locations

The Royal Berkshire and Battle Hospitals NHS Trust

Reading, , United Kingdom

Countries

United Kingdom

References

Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, Notcutt W, O'Leary C, Ratcliffe S, Novakova I, Zapletalova O, Pikova J, Ambler Z. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res. 2010 Jun;32(5):451-9. doi: 10.1179/016164109X12590518685660. Epub 2010 Mar 19.

Reference Type: RESULT

PMID: 20307378 (View on PubMed)

Di Marzo V, Centonze D. Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes. CNS Neurosci Ther. 2015 Mar;21(3):215-21. doi: 10.1111/cns.12358. Epub 2014 Dec 4.

Reference Type: DERIVED

PMID: 25475413 (View on PubMed)

Other Identifiers

GWCL0403

Identifier Type: -

Identifier Source: org_study_id