PainPhase 3NCT01606202
A Study of Cannabis Based Medicine Extracts and Placebo in Patients With Pain Due to Spinal Cord Injury
A Phase 3 study testing GW-1000-02 in people with Pain, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
A study to investigate the effects of sublingual cannabis based medicine extracts on neuropathic pain associated with spinal cord injury. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain
- What is being tested?
- GW-1000-02
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2002to Jan 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
- Gave informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Diagnosis of non-acute spinal cord injury, with central neuropathic pain not wholly relieved by current therapy.
- Central neuropathic pain with a mean severity Numerical Rating Scale score at least four during last seven days of the baseline period.
- Relatively stable neurology during the preceding six months.
- Stable medication regimen during the preceding four weeks.
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- Agreement, if female and of child bearing potential or if male with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.
- Had not used cannabinoids for at least the preceding seven days and willing to abstain from any use of cannabinoids during the study.
- Clinically acceptable laboratory results at Visit 2.
- Ability (in the investigator's opinion) and willingness to comply with all study requirements.
- Agreement for the UK Home Office, their general practitioner, and their consultant if appropriate, to be notified of their participation in the study.
Who cannot join
- History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- History of alcohol or substance abuse.
- Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
- History of autonomic dysreflexia.
- History of epilepsy.
- If female, were pregnant or lactating, or were planning a pregnancy to occur during the course of the study.
Show all 18Show fewer
- Significant renal or hepatic impairment.
- Elective surgery or other procedures requiring general anaesthesia scheduled to occur during the study.
- Terminal illness or were considered inappropriate for placebo medication.
- Any other significant disease or disorder which, in the opinion of the investigator, may have either put the subject at risk because of participation in the study, or may influenced the result of the study, or the subject's ability to participate in the study.
- Regular levodopa therapy within the seven days leading to study entry.
- If male, were receiving and were unwilling to stop sildenafil for the duration of the study.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
- Known or suspected adverse reaction to cannabinoids.
- Intention to travel internationally during the study.
- Intention to donate blood during the study.
- Participation in another research study in the 12 weeks leading to study entry.
- Previous randomisation into this study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Royal National Orthopaedic Hospital
Middlesex, HA7 4LP
About this study
Official title: A Randomised, Double Blind, Placebo Controlled, Parallel Group Comparative Study of the Efficacy, Safety and Tolerability of Sublingual Cannabis Based Medicine Extracts and Placebo in Patients With Intractable Neuropathic Pain Associated With Spinal Cord Injury
A study to investigate the effects of sublingual cannabis based medicine extracts on neuropathic pain associated with spinal cord injury.
Read the detailed description
This was a multi-centre, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and tolerability of GW-1000-02 in central neuropathic pain associated with spinal cord injury. Patients were screened to determine eligibility and completed a seven to 21 day baseline period. Patients then returned to the centre for assessment, randomisation and initial dosing. Visits occurred at the end of treatment week one and at the end of the study (treatment week three) or upon withdrawal. Throughout the study, patients were permitted to take paracetamol as escape analgesic to relieve breakthrough pain. Patients in this study could elect to be screened for an open label extension study of GW-1000-02.
- Conditions
- Pain
- Being tested
- GW-1000-02, Placebo
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GW-1000-02Drug
Also called Sativex
Contained delta-9-tetrahydrocannabinol (THC) (27 mg/ml):cannabidiol (CBD) (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg). The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period.
PlaceboDrug
Contained peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl. The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period.
| Study group | Role | What they receive |
|---|---|---|
| GW-1000-02 | Experimental | Active treatment. Receives: Drug: GW-1000-02 |
| Placebo | Placebo comparator | Placebo 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 Central Neuropathic Pain 11-Point Numerical Rating Scale Scores at the End of Treatment (up to 51 Days).
The Central Neuropathic Pain Numerical Rating Scale score was recorded three times daily, in the morning (on waking), at lunchtime and in the evening using the scale, 0 = 'No Pain' and 10 = 'Worst Possible Pain'. Patients were instructed to relate 'No Pain' to the time before the start of their spinal cord injury. End of Treatment was defined as the mean of the last seven days in the study or the mean of the last three days if the subject withdrew. A negative value indicates an improvement in pain score from baseline.
Measured: Up to 51 days
Secondary outcomes (13)
Change From Baseline in the Mean Percentage of Days on Which Escape Medication Was Used at the End of Treatment
The percentage of days that subjects used escape medication was analysed and is presented as the mean change from baseline at the end of treatment. A negative value from baseline indicates an improvement.
Measured: Up to 51 days
Change From Baseline in Mean Spasm Severity Numerical Rating Scale Score at the End of Treatment
Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day and, if yes, recorded the overall level of the spasm(s) experienced using an Numerical Rating Scale spasm scale ranging from 0 = "Mildest ever spasm" to 10 = "Worst ever spasm". The mean spasm severity scores were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.
Measured: Up to 51 days
Change From Baseline in the Percentage of Days on Which Spasm Was Experienced at the End of Treatment
Each day, just before going to bed, patients recorded in their patient diary whether they experienced any spasms that day. The percentage of days on which spasm was experienced were summarised and analysed analogously to the primary endpoint. A negative value from baseline indicates an improvement.
Measured: Up to 51 days
Change From Baseline in Mean Spasticity Severity Numerical Rating Scale Scores the End of Treatment.
Each day at bed time patients recorded whether they experienced any spasticity that day and, if yes, the overall level of spasticity experienced was quantified using an Numerical Rating Scale from 0 = "Mildest ever spasticity" to 10 = "Worst ever spasticity". The mean spasticity severity scores and the changes from baseline to End of Treatment were to be calculated. A negative value indicates an improvement from baseline.
Measured: 0 - 51 days
Change From Baseline in the Percentage of Days on Which Spasticity Was Experienced at the End of Treatment
Each day, just before going to bed, patients recorded in their patient diary whether they had experienced any spasticity that day or not. The percentage of days on which spasticity was experienced (spasticity incidence) was calculated and summarised analogously to the primary efficacy parameter of Numerical Rating Scale pain score. A negative value from baseline indicates an improvement.
Measured: Up to 51 days
Change From Baseline in Modified Ashworth Scale Score at the End of Treatment
The Modified Ashworth Scale is a five-point scale conducted on four pre-identified muscle groups. Only the lower limb was assessed because not all Spinal Cord Injury patients upper limb disability. The assessor used the Modified Ashworth scale ranging from 0 ("No increase in muscle tone") to 4 ("Affected part(s) rigid in flexion or extension") to rate the muscle tone for knee and ankle for the left and right sides separately at a pre-dose visit and at the end of treatment. The average of the four individual scores and was taken. A negative value indicates an improvement from baseline.
Measured: Up to 51 days
Change From Baseline in the Mean Short Orientation Memory Function Concentration Test Score at the End of Treatment
Patients were asked at baseline and end of treatment, to complete the Short Orientation Memory Function Concentration Test as a measure of cognitive function. The minimum score is 0 and maximum of 28 which denoted good cognitive function .
A negative value from baseline indicates a deterioration.
Measured: Up to 51 days
Change From Baseline in Mean Spitzer Quality of Life Index Score at the End of Treatment
The Spitzer Quality of Life Index questionnaire consists of five sections, relating to activity, daily living, health, support and outlook. Each section has three choices (numbered 1, 2 and 3) and the patient is required to choose the one that best describes their quality of life during the last week. Choice 1 is scored 2, choice 2 is scored 1 and choice 3 is scored 0. The total Spitzer is the unweighted sum of the five scores. The scale is 0 (bad) to 10 (good). A positive value indicates an improvement from baseline.
Measured: Up to 51 days
Change From Baseline in the Mean Caregiver Strain Index Score at the End of Treatment
Carers were asked at baseline and end of treatment to complete the Caregiver Strain Index, as a measure of the strain they felt from being a carer, the maximum possible score being 13. A negative value from baseline indicates an improvement.
Measured: Up to 51 days
Number of Subjects Who Reported an Improvement in Their Overall Condition in the Patient Global Impression of Change at the End of Treatment
The Patient Global Impression of Change asked patients to give their impression of the overall change in their condition during the study at the end of treatment using the following scale: 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, 7 = Very Much Worse. The number of patients who scored their condition as 1, 2, or 3 (improved) is presented.
Measured: Up to 51 days
Change From Baseline in the Mean Brief Pain Inventory Score at the End of Treatment
The Brief Pain Inventory 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 is calculated as the arithmetic mean of the four severity items(range 0-10). A negative value indicates an improvement in worst pain score from baseline.
Measured: 0 - 51 days
Change From Baseline in the Mean Sleep Disturbance Numerical Rating Scale Score at the End of Treatment
Each day patients recorded in their patient diary whether they woke during the previous night using the following scoring system: 0 = No, 1 = Once, 2 = Twice, 3 = More than twice, 4 = Awake most of the night. A negative value indicates an improvement from baseline.
Measured: 0 - 51 days
Incidence of Adverse Events as a Measure of Patient Safety.
The number of patients who experienced an adverse event during the study is presented.
Measured: Up to 61 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2012 (estimated)
- Study startJul 2002
- Primary completionJan 2005
- Study completionJan 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 (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies 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
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01606202
- Sponsor's protocol ID
- GWSC0101
- Status last verified
- Dec 2022
- First submitted
- 21 May 2012
- Last updated
- 10 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Thomas PA, Carter GT, Bombardier CH. A scoping review on the effect of cannabis on pain intensity in people with spinal cord injury. J Spinal Cord Med. 2022 Sep;45(5):656-667. doi: 10.1080/10790268.2020.1865709. Epub 2021 Jan 19.
PubMed 33465022
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double Blind, Placebo Controlled, Parallel Group Comparative Study of the Efficacy, Safety and Tolerability of Sublingual Cannabis Based Medicine Extracts and Placebo in Patients With Intractable Neuropathic Pain Associated With Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT01606202
- Acronym / sponsor ID
- GWSC0101
- Conditions
- Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2002
- Primary completion
- Jan 2005 (actual)
- Study completion
- Jan 2005 (actual)
- First posted
- 25 May 2012 (estimated)
- Results
- Posted 28 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to investigate the effects of sublingual cannabis based medicine extracts on neuropathic pain associated with spinal cord injury.
Detailed description
This was a multi-centre, double-blind, randomised, placebo-controlled, parallel-group study to evaluate the efficacy and tolerability of GW-1000-02 in central neuropathic pain associated with spinal cord injury. Patients were screened to determine eligibility and completed a seven to 21 day baseline period. Patients then returned to the centre for assessment, randomisation and initial dosing. Visits occurred at the end of treatment week one and at the end of the study (treatment week three) or upon withdrawal. Throughout the study, patients were permitted to take paracetamol as escape analgesic to relieve breakthrough pain. Patients in this study could elect to be screened for an open label extension study of GW-1000-02.
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 |
|---|---|---|
| GW-1000-02 | Experimental | Drug: GW-1000-02Active treatment. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo control. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Gave informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Diagnosis of non-acute spinal cord injury, with central neuropathic pain not wholly relieved by current therapy.
- Central neuropathic pain with a mean severity Numerical Rating Scale score at least four during last seven days of the baseline period.
- Relatively stable neurology during the preceding six months.
Key exclusion criteria (18 listed)
- History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- History of alcohol or substance abuse.
- Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
- History of autonomic dysreflexia.
- History of epilepsy.
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 |
|---|---|---|
| GW-1000-02Also: SativexContained delta-9-tetrahydrocannabinol (THC) (27 mg/ml):cannabidiol (CBD) (25 mg/ml) as extract of Cannabis sativa L., with peppermint oil, 0.05% (v/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl (THC 2.7 mg and CBD 2.5 mg). The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period. | Drug | GW-1000-02 |
| PlaceboContained peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient. Each actuation delivered 100 μl. The maximum permitted dose of study medication was eight actuations in any three-hour period, and 48 actuations in any 24 hour period. | Drug | Placebo |
Primary outcome
Change From Baseline in Mean Central Neuropathic Pain 11-Point Numerical Rating Scale Scores at the End of Treatment (up to 51 Days).
Time frame: Up to 51 days
The Central Neuropathic Pain Numerical Rating Scale score was recorded three times daily, in the morning (on waking), at lunchtime and in the evening using the scale, 0 = 'No Pain' and 10 = 'Worst Possible Pain'. Patients were instructed to relate 'No Pain' to the time before the start of their spinal cord injury. End of Treatment was defined as the mean of the last seven days in the study or the mean of the last three days if the subject withdrew. A negative value indicates an improvement in pain score from baseline.
13 secondary outcomes
Change From Baseline in the Mean Percentage of Days on Which Escape Medication Was Used at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in Mean Spasm Severity Numerical Rating Scale Score at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in the Percentage of Days on Which Spasm Was Experienced at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in Mean Spasticity Severity Numerical Rating Scale Scores the End of Treatment.
Time frame: 0 - 51 days
Change From Baseline in the Percentage of Days on Which Spasticity Was Experienced at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in Modified Ashworth Scale Score at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in the Mean Short Orientation Memory Function Concentration Test Score at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in Mean Spitzer Quality of Life Index Score at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in the Mean Caregiver Strain Index Score at the End of Treatment
Time frame: Up to 51 days
Number of Subjects Who Reported an Improvement in Their Overall Condition in the Patient Global Impression of Change at the End of Treatment
Time frame: Up to 51 days
Change From Baseline in the Mean Brief Pain Inventory Score at the End of Treatment
Time frame: 0 - 51 days
Change From Baseline in the Mean Sleep Disturbance Numerical Rating Scale Score at the End of Treatment
Time frame: 0 - 51 days
Incidence of Adverse Events as a Measure of Patient Safety.
Time frame: Up to 61 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33465022Thomas PA, Carter GT, Bombardier CH. A scoping review on the effect of cannabis on pain intensity in people with spinal cord injury. J Spinal Cord Med. 2022 Sep;45(5):656-667. doi: 10.1080/10790268.2020.1865709. Epub 2021 Jan 19.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 GW-1000-02 in people with Pain, 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 11 inclusion and 18 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 10 Jan 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 28 Sep 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 Central Neuropathic Pain 11-Point Numerical Rating Scale Scores at the End of Treatment (up to 51 Days). (time frame: Up to 51 days). 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 NCT01606202, 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 10 Jan 2023.