Multiple SclerosisPhase 3NCT01599234
A Study to Evaluate the Efficacy of Sativex in Relieving Symptoms of Spasticity Due to Multiple Sclerosis
A Phase 3 study testing Sativex in people with Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study was to assess the efficacy of Sativex in relieving symptoms of spasticity in multiple sclerosis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Sativex
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 337 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2005to Dec 2005
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Royal Berkshire and Battle Hospitals NHS Trust
Reading, RG1 5AN
About this study
Official title: A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Sativex, in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis.
The purpose of this study was to assess the efficacy of Sativex in relieving symptoms of spasticity in multiple sclerosis
Read the 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
- Being tested
- Sativex, Placebo
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SativexDrug
Also called GW-1000-02
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Experimental | Active treatment Receives: Drug: Sativex |
| Placebo | Placebo comparator | Control Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The cumulative response to treatment was the percentage change from baseline in the mean NRS spasticity score as defined as the 30% response. The 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. The number of responders at the 30% level is presented.
Measured: 0-15 weeks
Change From Baseline in the Mean Modified Ashworth Scale Score at the End of Treatment
All 20 muscle groups were assessed for spasticity (using a 1-5 scale): 1= no increase in muscle tone to 5= passive movement is difficult and affected part is rigid in flexion or extension. The score for all 20 muscle groups were added to give a total score out of 100; minimum score was 20. A decrease in score indicates an improvement in condition.
Measured: 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)
The sleep disruption 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 how your spasticity disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Measured: 0-15 weeks
Incidence of Adverse Events as a Measure of Subject Safety
The number of subjects who experienced and adverse event during the course of the study is presented
Measured: 0-15 weeks
Change From Baseline in Mean Timed 10 Metre Walk Time at the End of Treatment
Only those subjects for whom it was appropriate (i.e. ambulatory subjects) were timed how long it took to walk 10 metres. Walk time was only assessed for subjects who successfully completed the Timed 10 Metre Walk. A negative difference from baseline indicates an improvement walk time.
Measured: Day 0 (Randomisation) and Day 99 (End of Treatment)
Carer Global Impression of Change at the End of Treatment
The carer of the subject gave their opinion of any noticeable change in the subject's overall functional ability at the end of the study. A 7-point Likert-type scale was used, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". The number of carers who reported an improvement at the end of treatment is presented.
Measured: Day 99 (end of treatment)
Change From Baseline in the Mean Total Barthel Activities of Daily Living Index Score at the End of Treatment
The Barthel Index consists of 10 items that measure a person's daily functioning specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and return, grooming, transferring to and from a toilet, bathing, walking on level surface, going up and down stairs, dressing, continence of bowels and bladder. The person receives a score based on whether they have received help while doing the task. The scores for each of the items are summed to create a total score of 100. An increase in score indicates an improvement.
Measured: Day 0 (Randomisation) and Day 99 (End of Treatment)
Number of Subjects With a 50% or Greater Improvement in Mean Spasticity 0-10 NRS Score at the End of Treatment Compared to Baseline
The cumulative response to treatment was the percentage change from baseline in the mean NRS spasticity score as defined as the 50% response. The 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. The number of responders at the 50% level is presented.
Measured: 0 - 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2012 (estimated)
- Study startMar 2005
- Primary completionDec 2005
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 337 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christine Collin, Principal investigator, The Royal Berkshire and Battle Hospitals NHS Trust, London Road, Reading, Berkshire, RG1 5AN.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01599234
- Sponsor's protocol ID
- GWCL0403
- Status last verified
- Apr 2023
- First submitted
- 10 May 2012
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 20307378Di 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.
PubMed 25475413
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Sativex, in Subjects With Symptoms of Spasticity Due to Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT01599234
- Acronym / sponsor ID
- GWCL0403
- Conditions
- Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 337 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Mar 2005
- Primary completion
- Dec 2005 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 15 May 2012 (estimated)
- Results
- Posted 16 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sativex | Experimental | Drug: SativexActive treatment |
| Placebo | Placebo comparator | Drug: PlaceboControl |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SativexAlso: GW-1000-02Contains 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. | Drug | Sativex |
| PlaceboContains 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. | Drug | Placebo |
Primary outcome
Change From Baseline in Mean Spasticity 0-10 Numerical Rating Scale (NRS) Score During the Last 14 Day of Treatment (End of Treatment)
Time frame: 0-15 weeks
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.
8 secondary outcomes
Number of Subjects With a 30% or Greater Improvement in Mean Spasticity 0-10 NRS Score at the End of Treatment Compared to Baseline
Time frame: 0-15 weeks
Change From Baseline in the Mean Modified Ashworth Scale Score at the End of Treatment
Time frame: 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)
Time frame: 0-15 weeks
Incidence of Adverse Events as a Measure of Subject Safety
Time frame: 0-15 weeks
Change From Baseline in Mean Timed 10 Metre Walk Time at the End of Treatment
Time frame: Day 0 (Randomisation) and Day 99 (End of Treatment)
Carer Global Impression of Change at the End of Treatment
Time frame: Day 99 (end of treatment)
Change From Baseline in the Mean Total Barthel Activities of Daily Living Index Score at the End of Treatment
Time frame: Day 0 (Randomisation) and Day 99 (End of Treatment)
Number of Subjects With a 50% or Greater Improvement in Mean Spasticity 0-10 NRS Score at the End of Treatment Compared to Baseline
Time frame: 0 - 15 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20307378Collin 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.
- Derived from this study: PubMed 25475413Di 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Collin principal investigator
The Royal Berkshire and Battle Hospitals NHS Trust, London Road, Reading, Berkshire, RG1 5AN.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sativex in people with Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Mean Spasticity 0-10 Numerical Rating Scale (NRS) Score During the Last 14 Day of Treatment (End of Treatment) (time frame: 0-15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01599234, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.