Multiple SclerosisPhase 3NCT00391079

Sativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS

A Phase 3 study testing Sativex in people with Multiple Sclerosis, run by GW Pharmaceuticals Ltd at 6 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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: 339 participants
Where: 6 sitesCanada
Study dates: Sep 2006to Sep 2008
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

Any disease sub-type of MS of at least two years duration
Central neuropathic pain (CNP) of at least three months and expected to remain stable for the study duration
Moderate CNP defined by NRS pain score at baseline sum to at least 24
Subject established on or previously tried and failed analgesic therapy for CNP
If receiving disease modifying medications, stable dose for 3 months and maintained for study duration

Who cannot join

Subjects whose identified pain is likely to be nociceptive, musculoskeletal (including spasms) peripheral neuropathic or psychogenic in origin, or due to trigeminal neuralgia.
Other non central neuropathic pain of a severity which is likely to interfere with the patients assessment of CNP
medical history suggests subject is likely to relapse/remit during course of study
history of schizophrenia (including family history), other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with MS
known or suspected history of alcohol abuse, epilepsy or recurrent seizures or hypersensitivity to cannabinoids
travel outside of the country of residence planned during the study
significant cardiac, renal or hepatic impairment
subjects with current recreational cannabis, medicinal cannabis or synthetic cannabinoid based medications within 3 months prior to study entry and unwilling to abstain for the duration of the study

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

Canada6 sites

Multiple Sclerosis Program, Foothills Hospital SSB
Calgary, Alberta, T2N 2T9
Dalhousie MS Research Clinic
Halifax, Nova Scotia, B3H 1V8
London Health Sciences Centre / University Hospital
London, Ontario, N6A 5A5
Montreal Neurological Institute
Montreal, Quebec, H3 A 2B4
Ottawa Hospital General Campus
Ottawa, Ontario, K1H 8L6
MS Clinic, UBC Purdy Pavilion
Vancouver, British Columbia, V6T 2B5

Other trials in Canada

About this study

Official title: A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Sativex When Added to the Existing Treatment Regimen, in the Relief of Central Neuropathic Pain in Subjects With Multiple Sclerosis

The purpose of this study is to find out if cannabis-based medicine compared to a dummy medicine (placebo that contains no active ingredient) can help the central neuropathic pain patients experience as a result of multiple sclerosis. This type of pain "central neuropathic pain" is described as shooting, stabbing, burning or searing like sensation, which is often worse at night.

Read the detailed description

GW has shown in phase II and III studies that Sativex has analgesic properties that are effective in relieving neuropathic pain. These studies suggested that Sativex is well tolerated and may also improve sleep and quality of life. GW is conducting this study to further demonstrate these effects.

Conditions: Multiple Sclerosis
Being tested: Sativex, Placebo
Keywords: Central Neuropathic Pain
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
Containing D9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L.
Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays (THC 32.5 mg: CBD 30 mg.
PlaceboDrug
Also called GA0034
Containing colourants and excipients. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays.

Study groups in NCT00391079
Study group	Role	What they receive
A	Experimental	Not described Receives: Drug: Sativex
B	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Mean Pain Due to MS NRS Score
The pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. A negative value indicates an improvement in pain score from baseline.
Measured: 14 weeks: Baseline - End of Treatment (last 7 days of treatment)
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Pain Score From Baseline
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS pain score from baseline to week 14 (last 7 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. The pain NRS was completed at the same time each day, i.e. bedtime in the evening.
Measured: 14 weeks: Baseline - end of treatment (last 7 days)

Secondary outcomes (5)

Change in Pain From Baseline to End of the Treatment Using the NPS (Neuropathic Pain Scale)
The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Measured: 14 weeks: Baseline - End of treatment (Week 14)
Change From Baseline to End of Treatment in Break-through Analgesia Usage
Use of break through medication was recorded daily during the 14 weeks of the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Measured: 14 weeks: baseline - end of treatment (last 7 days)
Change From Baseline to End of Treatment in BPI (Brief Pain Inventory) Short Form
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Measured: 14 weeks: Baseline to end of treatment (last 7 days of treatment)
Change in Subject Global Impression of Change (SGIC)
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to multiple sclerosis since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At baseline subjects wrote a brief description of their pain caused by multiple sclerosis which was used at Week 14 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Measured: Week 14
Change in Sleep Disruption NRS
The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain 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: 14 weeks; Baseline to end of treatment (last 7 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2006Sep 2008

First posted23 Oct 2006 (estimated)
Study startSep 2006
Primary completionApr 2008
Study completionSep 2008

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 (1)Papers the sponsor has linked to this study.
Other trials for Multiple SclerosisStudies of the same condition, open and under way.
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: Double blind
Who is masked: Participant, Investigator
Enrolment: 339 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00391079
Sponsor's protocol ID: GWMS0501
Status last verified: Jun 2013
First submitted: 20 Oct 2006
Last updated: 24 Jun 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013 Apr;260(4):984-97. doi: 10.1007/s00415-012-6739-4. Epub 2012 Nov 21.
PubMed 23180178

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2013. 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 When Added to the Existing Treatment Regimen, in the Relief of Central Neuropathic Pain in Subjects With Multiple Sclerosis
ClinicalTrials.gov ID: NCT00391079
Acronym / sponsor ID: GWMS0501
Conditions: Multiple Sclerosis
Keywords: Central Neuropathic Pain
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 339 participants (actual)
Lead sponsor: GW Pharmaceuticals LtdIndustry (pharma, biotech, devices)
Study start: Sep 2006
Primary completion: Apr 2008 (actual)
Study completion: Sep 2008 (actual)
First posted: 23 Oct 2006 (estimated)
Results: Posted 4 Jul 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
A	Experimental	Drug: Sativex
B	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Any disease sub-type of MS of at least two years duration
Central neuropathic pain (CNP) of at least three months and expected to remain stable for the study duration
Moderate CNP defined by NRS pain score at baseline sum to at least 24
Subject established on or previously tried and failed analgesic therapy for CNP
If receiving disease modifying medications, stable dose for 3 months and maintained for study duration

Key exclusion criteria (8 listed)

Subjects whose identified pain is likely to be nociceptive, musculoskeletal (including spasms) peripheral neuropathic or psychogenic in origin, or due to trigeminal neuralgia.
Other non central neuropathic pain of a severity which is likely to interfere with the patients assessment of CNP
medical history suggests subject is likely to relapse/remit during course of study
history of schizophrenia (including family history), other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with MS
known or suspected history of alcohol abuse, epilepsy or recurrent seizures or hypersensitivity to cannabinoids

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-1000-02Containing D9 tetrahydrocannabinol (THC), 27 mg/ml: cannabidiol (CBD), 25 mg/ml, as extracts of Cannabis sativa L. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays (THC 32.5 mg: CBD 30 mg.	Drug	A
PlaceboAlso: GA0034Containing colourants and excipients. Delivered in 100 µl actuations by a pump action oromucosal spray. Maximum dose within any 24-hour interval 12 sprays.	Drug	B

Primary outcome

Change in Mean Pain Due to MS NRS Score
Time frame: 14 weeks: Baseline - End of Treatment (last 7 days of treatment)
The pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. A negative value indicates an improvement in pain score from baseline.
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Pain Score From Baseline
Time frame: 14 weeks: Baseline - end of treatment (last 7 days)
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS pain score from baseline to week 14 (last 7 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to multiple sclerosis. The pain NRS was completed at the same time each day, i.e. bedtime in the evening.

5 secondary outcomes

Change in Pain From Baseline to End of the Treatment Using the NPS (Neuropathic Pain Scale)
Time frame: 14 weeks: Baseline - End of treatment (Week 14)
Change From Baseline to End of Treatment in Break-through Analgesia Usage
Time frame: 14 weeks: baseline - end of treatment (last 7 days)
Change From Baseline to End of Treatment in BPI (Brief Pain Inventory) Short Form
Time frame: 14 weeks: Baseline to end of treatment (last 7 days of treatment)
Change in Subject Global Impression of Change (SGIC)
Time frame: Week 14
Change in Sleep Disruption NRS
Time frame: 14 weeks; Baseline to end of treatment (last 7 days)

Results and safety

Results posted to the registry on 4 Jul 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sativex	167	141
Placebo	172	156

Primary outcome: Change in Mean Pain Due to MS NRS Score

Time frame: 14 weeks: Baseline - End of Treatment (last 7 days of treatment). Mean (Standard Deviation). Unit: units on a scale

Measure	Sativex n = 167	Placebo n = 172
Value	-2.02 (2.15)	-1.89 (2.33)

Sativex vs Placebo: Estimated treatment effect: -0.17 (95% CI -0.62 to 0.29), p = 0.468, ANCOVA

Population analysed: Change in mean daily NRS score

Primary outcome: Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Pain Score From Baseline

Time frame: 14 weeks: Baseline - end of treatment (last 7 days). Number. Unit: participants

Measure	Sativex n = 167	Placebo n = 172
Value	84	77

Sativex vs Placebo: Odds Ratio (OR): 1.309 (95% CI 0.840 to 2.038), p = 0.2338, Regression, Logistic

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events occurring from time of consent to post study follow up i.e. 15 weeks were collected. All deaths and serious adverse events occurring within 28 days of the final dose of study medications were also collected/. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sativex	3 of 167 (1.8%)	99 of 167 (59.3%)	Not reported
Placebo	2 of 172 (1.2%)	65 of 172 (37.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23180178Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, Ratcliffe S. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013 Apr;260(4):984-97. doi: 10.1007/s00415-012-6739-4. Epub 2012 Nov 21.

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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.

Gerard S Barron, BSc study director

GW Pharma Ltd

6 sites 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 GW Pharmaceuticals Ltd at 6 sites in Canada.

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 5 inclusion and 8 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 24 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Canada. 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 4 Jul 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 in Mean Pain Due to MS NRS Score (time frame: 14 weeks: Baseline - End of Treatment (last 7 days of treatment)). The study lists 2 primary outcomes in all. 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 NCT00391079, which also lists 1 linked publication.

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 24 Jun 2013.