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

NCT01599234 | Completed Phase 3 Results

• 1 other identifier: GWCL0403
• Study Type: interventional
• Target: 337
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean Spasticity 0-10 Numerical Rating Scale (NRS) Score During the Last 14 Day of Treatment (End of Treatment)

  The average spasticity NRS was completed at the same time each day, i.e. bedtime in the evening. The subject was asked "on a scale of '0 to 10', please indicate the number that best describes your spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst possible spasticity. A negative value indicates an improvement in pain score from baseline.

  0-15 weeks

Secondary Outcomes (8)

• Number of Subjects With a 30% or Greater Improvement in Mean Spasticity 0-10 NRS Score at the End of Treatment Compared to Baseline

  0-15 weeks

• Change From Baseline in the Mean Modified Ashworth Scale Score at the End of Treatment

  Day 0 (Randomisation) and Day 99 (End of Treatment)

• Change From Baseline in Mean Sleep Quality 0-10 NRS During the Last 14 Days of Treatment (End of Treatment)

  0-15 weeks

• Incidence of Adverse Events as a Measure of Subject Safety

  0-15 weeks

• Change From Baseline in Mean Timed 10 Metre Walk Time at the End of Treatment

  Day 0 (Randomisation) and Day 99 (End of Treatment)

Study Arms (2)

Sativex

EXPERIMENTAL

Active treatment

Drug: Sativex

Placebo

PLACEBO COMPARATOR

Control

Drug: Placebo

Interventions

Sativex 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.

Also known as: GW-1000-02

Sativex

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (1)

The Royal Berkshire and Battle Hospitals NHS Trust

Reading, RG1 5AN, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 20307378 RESULT

• 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.

  PMID: 25475413 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Mr Richard Potts, Clinical Operations Director
• Organization: GW Pharma Ltd.

rp@gwpharm.com

0044 1223 266800

Study Officials

• Christine Collin

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 15, 2012
• Study Start: March 1, 2005
• Primary Completion: December 1, 2005
• Study Completion: December 1, 2005
• Last Updated: May 3, 2023
• Results First Posted: August 16, 2012

Record last verified: 2023-04

Locations

GB (1)