PainPhase 3NCT01606189
A Study to Compare Sublingual Cannabis Based Medicine Extracts With Placebo to Treat Brachial Plexus Injury Pain
A Phase 3 study testing GW-1000-02 and GW-2000-02 in people with Pain, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
A study to compare the efficacy of two sublingual cannabinoid based medicine extracts with placebo in the treatment of chronic pain due to brachial plexus 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 and GW-2000-02
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2001to Sep 2002
- 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
- Aged 18 years or above.
- Brachial plexus pain, at least 18 months after the initial injury.
- Reported weekly brachial plexus pain at the required severity at Visits 1 and 2; a Box Scale-11 pain severity score of four boxes or above.
- A pattern of pain that in the Investigator's opinion had been stable during the four weeks before study entry.
- Stable regular medication during the four weeks before study entry.
- A maximum tricyclic antidepressant dose of 75 mg per day, if applicable.
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- No cannabinoid use (cannabis, Marinol® or Nabilone) at least seven days before study entry or during the study.
- If sexually active; was either using effective contraception during the study and for three months thereafter or had been surgically sterilised or, if female, was post-menopausal. All patients agreed to use a barrier method of contraception in addition to their usual form of oral or depot contraception.
- Willing and able to undertake and comply with all study requirements.
- Willing and able to consider and understand the patient information leaflet and consent form and to give informed consent. Those patients unable to read or to sign the document were managed as detailed in the Declaration of Helsinki.
- Willing for his or her general practitioner, and consultant if appropriate, to be informed of study participation.
- Willing for his or her name to be notified to Home Office for participation in the study.
Who cannot join
- Abuse or strong suspicion of drug abuse, including alcohol or cannabis, or in the investigator's opinion had a tendency to drug dependency or substance abuse. Patients with a history of abuse could have been included at the discretion of the investigator.
- Known or suspected adverse reaction to cannabinoids.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication.
- History of any type of schizophrenia, any other psychotic illness, or other significant psychiatric illness other than depression associated with chronic illness.
- Regular levodopa therapy (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®) within seven days of study entry.
- Serious cardiovascular disorder including recent angina, uncontrolled hypertension or an uncontrolled symptomatic cardiac arrhythmia.
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- History of significant renal or hepatic impairment as shown in medical history or indicated by clinical laboratory results from samples.
- History of active epilepsy or convulsions.
- Nerve surgery within six months of study entry or any other surgery within two months of study entry.
- Elective surgery, other procedures requiring general anaesthesia, or a planned hospital admission that would have taken place during the study, other than a hospital admission under the care of the study investigator.
- Terminal illness.
- Pregnancy, lactation or expected non-compliance with the contraceptive measures called for by the protocol.
- Participation in any other pharmacological clinical research study in the 12 weeks before study entry.
- Planned travel outside the UK between study entry and the end of the crossover phase.
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 Double Blind, Randomised, Three Way Crossover Study Comparing Two Different Sublingual Cannabis Based Medicine Extracts With Placebo, in Patients With Chronic Pain Due to Brachial Plexus Injury.
A study to compare the efficacy of two sublingual cannabinoid based medicine extracts with placebo in the treatment of chronic pain due to brachial plexus injury.
Read the detailed description
This study used a three way crossover study design. Eligible patients recorded their symptoms during a one to two week baseline period, then entered a three period, double blind, randomised crossover of GW-1000-02, GW-2000-02 and placebo. Each period lasted two weeks, with no washout between periods. There were six possible treatment sequences. The primary analysis was based on Box Scale-11 pain severity scores recorded throughout the study in patient daily diary booklets. Blood samples were taken from patient-volunteers at the beginning of each period, for measurement of plasma cannabinoid concentration.
- Conditions
- Pain
- Being tested
- GW-1000-02, GW-2000-02, 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
Contains delta-9-tetrahydrocannabinol (THC) (25 mg/ml) and cannabidiol (CBD) (25mg/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 2.5 mg and CBD 2.5 mg). The maximum daily exposure was set at 48 actuations per day.
GW-2000-02Drug
Contains THC (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 2.5 mg). The maximum daily exposure was set at 48 actuations per day.
PlaceboDrug
Contains 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 daily exposure was set at 48 actuations per day.
| Study group | Role | What they receive |
|---|---|---|
| GW-1000-02 | Experimental | Active treatment. Receives: Drug: GW-1000-02 |
| GW-2000-02 | Experimental | Active treatment. Receives: Drug: GW-2000-02 |
| 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 the Mean Box Scale-11 Pain Review Score at the End of Each Treatment Period (Each Lasting 14-20 Days)
Each day patients recorded in their patient diary, the severity of their pain during the previous 24 hours using a Box Scale-11 pain score ranging from zero "no pain at all" to 10 "pain as bad as you can imagine". The Box Scale-11 pain score endpoint for each assessment period was the average of all available data recorded during the seven whole days prior to the visit immediately subsequent to that period, but only including data from Day 8 onwards. A negative value indicates an improvement in pain score from baseline.
Measured: Up to 74 days
Secondary outcomes (8)
Change From Baseline in the Mean Sleep Disturbance Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
Each day patients recorded in their patient diary the number of times they were woken due to pain during the previous night. The results were recorded as "None", "Once", "Twice" and "More Than Twice" and converted to a four point scale, zero to three respectively. The treatment days and the assessment periods were defined in the same way as for the Box Scale-11 pain score. A negative value indicates an improvement from baseline.
Measured: Up to 74 days
Change From Baseline in the Mean Box Scale-11 Sleep Quality Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
Each day patients recorded in their patient diary the quality of their sleep during the previous night using a Box Scale-11 sleep score ranging from zero "Worst Imaginable" to 10 "Best Imaginable". The treatment days and the assessment periods were defined in the same way as for the Box Scale-11 pain score. A positive value indicates an improvement from baseline.
Measured: Up to 74 days
Change From Baseline in the Mean McGill Pain Questionnaire Part 1 Score for 'Total Pain Intensity' at the End of Each Treatment Period (Each Lasting 14-20 Days)
Part 1 of the questionnaire related to the intensity of 15 different types of pain. Intensity was recorded separately for each type of pain on a zero to three scale, where zero = "None", one = "Mild", two = "Moderate" and three = "Severe". The total intensity was defined as the unweighted sum of the 15 scores, giving a minimum possible score of zero (lowest pain score) and a maximum possible score of 45 (highest pain score). The distribution of each of the 15 types of pain was summarised at baseline and for each treatment. A negative value indicates an improvement in pain from baseline.
Measured: Up to 74 days
Change From Baseline in the Mean McGill Pain Questionnaire Part 2 Score for 'Intensity of Pain' at the End of Each Treatment Period (Each Lasting 14-20 Days)
Part 2 of the questionnaire recorded the intensity of pain at present. Results were recorded on a VAS ranging from zero "No pain" to 100 "Worst possible pain". Intensity of pain was summarised and analysed in the same manner as the primary efficacy parameter of Box Scale-11 pain score. A negative value indicates an improvement from baseline.
Measured: Up to 74 days
Change From Baseline in the Number of Patients Who Reported 'No Pain' or 'Mild Pain' Using a McGill Pain Questionnaire Part 3 Score for 'Strength of Pain at Present' at the End of Each Treatment Period (Each Lasting 14-20 Days)
Part 3 of the questionnaire recorded the strength of pain at present. Results were recorded in six categories which were classified as "No Pain", "Mild", "Discomforting", "Distressing", "Horrible" and "Excruciating". The change from baseline in the number of patients who reported "No Pain" or "Mild Pain" at the end of the respective treatment periods is presented. An increase in number indicates an improvement from baseline.
Measured: Up to 74 days
Change From Baseline in the Mean Pain Disability Index Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
The Pain Disability Index consisted of seven assessments representing different aspects of disability due to pain. Each assessment was scored on a zero to 10 scale, where zero equated with "no disability" and 10 equated with "total disability". The total Pain Disability Index score was the unweighted sum of the seven pain scores, ranging from zero to 70. A negative value indicates an improvement from baseline.
Measured: Up to 74 days
Change From Baseline in the Mean 12-Item General Health Questionnaire Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
The 12-Item General Health Questionnaire consisted of 12 general health questions. Each question was scored on a zero to three scale, where zero represented the better assessment. The total score was the unweighted sum of the 12 scores, ranging from zero to 36. A negative value indicates an improvement from baseline.
Measured: Up to 74 days
Incidence of Adverse Events as a Measure of Patient Safety.
The number of patients who experienced an adverse event during the course of study is presented.
Measured: Up to 114 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 startDec 2001
- Primary completionSep 2002
- Study completionSep 2002
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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 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
- NCT01606189
- Sponsor's protocol ID
- GWBP0101
- Status last verified
- Dec 2022
- First submitted
- 23 May 2012
- Last updated
- 10 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004 Dec;112(3):299-306. doi: 10.1016/j.pain.2004.09.013.
PubMed 15561385
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 Double Blind, Randomised, Three Way Crossover Study Comparing Two Different Sublingual Cannabis Based Medicine Extracts With Placebo, in Patients With Chronic Pain Due to Brachial Plexus Injury.
- ClinicalTrials.gov ID
- NCT01606189
- Acronym / sponsor ID
- GWBP0101
- Conditions
- Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2001
- Primary completion
- Sep 2002 (actual)
- Study completion
- Sep 2002 (actual)
- First posted
- 25 May 2012 (estimated)
- Results
- Posted 19 Nov 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 compare the efficacy of two sublingual cannabinoid based medicine extracts with placebo in the treatment of chronic pain due to brachial plexus injury.
Detailed description
This study used a three way crossover study design. Eligible patients recorded their symptoms during a one to two week baseline period, then entered a three period, double blind, randomised crossover of GW-1000-02, GW-2000-02 and placebo. Each period lasted two weeks, with no washout between periods. There were six possible treatment sequences. The primary analysis was based on Box Scale-11 pain severity scores recorded throughout the study in patient daily diary booklets. Blood samples were taken from patient-volunteers at the beginning of each period, for measurement of plasma cannabinoid concentration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GW-1000-02 | Experimental | Drug: GW-1000-02Active treatment. |
| GW-2000-02 | Experimental | Drug: GW-2000-02Active 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 (12 listed)
- Aged 18 years or above.
- Brachial plexus pain, at least 18 months after the initial injury.
- Reported weekly brachial plexus pain at the required severity at Visits 1 and 2; a Box Scale-11 pain severity score of four boxes or above.
- A pattern of pain that in the Investigator's opinion had been stable during the four weeks before study entry.
- Stable regular medication during the four weeks before study entry.
Key exclusion criteria (14 listed)
- Abuse or strong suspicion of drug abuse, including alcohol or cannabis, or in the investigator's opinion had a tendency to drug dependency or substance abuse. Patients with a history of abuse could have been included at the discretion of the investigator.
- Known or suspected adverse reaction to cannabinoids.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medication.
- History of any type of schizophrenia, any other psychotic illness, or other significant psychiatric illness other than depression associated with chronic illness.
- Regular levodopa therapy (Sinemet®, Sinemet plus®, Levodopa®, L-dopa®, Madopar®, Benserazide®) within seven days of study entry.
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: SativexContains delta-9-tetrahydrocannabinol (THC) (25 mg/ml) and cannabidiol (CBD) (25mg/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 2.5 mg and CBD 2.5 mg). The maximum daily exposure was set at 48 actuations per day. | Drug | GW-1000-02 |
| GW-2000-02Contains THC (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 2.5 mg). The maximum daily exposure was set at 48 actuations per day. | Drug | GW-2000-02 |
| PlaceboContains 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 daily exposure was set at 48 actuations per day. | Drug | Placebo |
Primary outcome
Change From Baseline in the Mean Box Scale-11 Pain Review Score at the End of Each Treatment Period (Each Lasting 14-20 Days)
Time frame: Up to 74 days
Each day patients recorded in their patient diary, the severity of their pain during the previous 24 hours using a Box Scale-11 pain score ranging from zero "no pain at all" to 10 "pain as bad as you can imagine". The Box Scale-11 pain score endpoint for each assessment period was the average of all available data recorded during the seven whole days prior to the visit immediately subsequent to that period, but only including data from Day 8 onwards. A negative value indicates an improvement in pain score from baseline.
8 secondary outcomes
Change From Baseline in the Mean Sleep Disturbance Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
Time frame: Up to 74 days
Change From Baseline in the Mean Box Scale-11 Sleep Quality Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
Time frame: Up to 74 days
Change From Baseline in the Mean McGill Pain Questionnaire Part 1 Score for 'Total Pain Intensity' at the End of Each Treatment Period (Each Lasting 14-20 Days)
Time frame: Up to 74 days
Change From Baseline in the Mean McGill Pain Questionnaire Part 2 Score for 'Intensity of Pain' at the End of Each Treatment Period (Each Lasting 14-20 Days)
Time frame: Up to 74 days
Change From Baseline in the Number of Patients Who Reported 'No Pain' or 'Mild Pain' Using a McGill Pain Questionnaire Part 3 Score for 'Strength of Pain at Present' at the End of Each Treatment Period (Each Lasting 14-20 Days)
Time frame: Up to 74 days
Change From Baseline in the Mean Pain Disability Index Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
Time frame: Up to 74 days
Change From Baseline in the Mean 12-Item General Health Questionnaire Score at the End of Each Treatment Period (Each Lasting 14-20 Days).
Time frame: Up to 74 days
Incidence of Adverse Events as a Measure of Patient Safety.
Time frame: Up to 114 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.
- Results publication: PubMed 15561385Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 2004 Dec;112(3):299-306. doi: 10.1016/j.pain.2004.09.013.
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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 and GW-2000-02 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 12 inclusion and 14 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 19 Nov 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 the Mean Box Scale-11 Pain Review Score at the End of Each Treatment Period (Each Lasting 14-20 Days) (time frame: Up to 74 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 NCT01606189, 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.