PainPhase 3NCT01606176
A Study to Evaluate the Effects of Cannabis Based Medicine in Patients With Pain of Neurological Origin
A Phase 3 study testing GW-1000-02 in people with Pain and Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
To investigate the ability of a cannabis based medicine extract to relieve chronic refractory pain of neurological origin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Multiple Sclerosis
- What is being tested?
- GW-1000-02
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2002to Aug 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
- Patient, or legal representative, willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Diagnosed with chronic refractory pain due to Multiple Sclerosis or other defects of neurological function.
- Diagnosed with pain, not wholly alleviated with current analgesic therapy at Visit 1 and an average score of over 4 on a Box Scale-11 scale on the four consecutive days leading up to Visit 2, where: zero = "no pain" and 10 = "worst possible pain".
- Stable dose of pain relieving medication for at least two weeks prior to study entry.
- Willing to ensure that they or their partner use effective contraception during the study and for three months thereafter (applicable to female patients of child bearing potential and male patients whose partners were of child bearing potential).
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- No cannabinoid use (cannabis, Marinol or Nabilone) for at least seven days before Visit 1 and be willing to abstain from any use of cannabis during the study.
- Able (in the investigator's opinion) and willing to comply with all study requirements.
- Willing for his or her name to be notified to the Home Office for participation in this study.
- Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of 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.
- Known 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 epilepsy.
- Female patients who were pregnant, lactating or planning pregnancy during the course of the study.
- Significant renal or hepatic impairment.
Show all 17Show fewer
- Scheduled elective surgery or other procedures requiring general anaesthesia during the study.
- Terminally ill or inappropriate for placebo medication.
- Any other significant disease or disorder which, in the opinion of the investigator, may have put the patient at risk because of participation in the study, or may have influenced the result of the study, or the patient's ability to participate in the study.
- Regular levodopa (Sinemet®, Sinemet Plus®, Levodopa, L-dopa, Madopar®, Benserazide) therapy within seven days of study entry.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
- Known or suspected of having adverse reaction to cannabinoids.
- Travel outside the UK planned during the study.
- Donation of blood during the study.
- Patients who had participated in another research study in the 12 weeks leading up to study entry.
- Patients who had been previously randomised into this study.
- Male patients who were receiving Sildenafil (Viagra®) at the time of study entry and were unwilling to stop medication for the duration of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi Centre Randomised, Double Blind, Placebo Controlled, Parallel Group Comparison of the Effects of Cannabis Based Medicine Standardised Extracts Over 4 Weeks, in Patients With Chronic Refractory Pain Due to Multiple Sclerosis or Other Defects of Neurological Function.
To investigate the ability of a cannabis based medicine extract to relieve chronic refractory pain of neurological origin.
Read the detailed description
Patients with Multiple Sclerosis or other defect of neurological function with a qualifying symptom of chronic refractory pain, entered a seven day baseline period, followed by a 21 day randomised, double blind, parallel group comparison of GW-1000-02 with placebo, self-titrated to symptom resolution or maximum tolerated dose. The ability of the cannabis based medicine extract to relieve chronic refractory pain was assessed by the change from baseline in pain score using Box Scale-11 (BS-11) scores recorded in the patients' daily diary.
- Conditions
- Pain, Multiple Sclerosis
- Being tested
- GW-1000-02, Placebo
- Medical subject headings
- Pain, Multiple Sclerosis
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
Each actuation of GW-1000-02 (100 μl) delivered a dose containing 2.5 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). The maximum permitted dose of study medication was eight actuations in any three hour period (20 mg THC/20 mg CBD) and 48 actuations in any 24 hour period (120 mg THC/120 mg CBD).
PlaceboDrug
Each actuation of placebo (100 μl) delivered the excipients only. 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 | Each 100 μl actuation contains 2.5 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). The maximum permitted dose was 48 actuations in any 24 hour period (120 mg THC/120 mg CBD). Receives: Drug: GW-1000-02 |
| Placebo | Placebo comparator | Each 100 μl actuation contains the excipients only. The maximum permitted dose was 48 actuations in any 24 hour period 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 Pain Box Scale-11 Score at 3 Weeks.
Each day, in the morning (on waking), at lunchtime and in the evening (just before going to bed), patients recorded in their patient diary their level of pain using a Box Scale-11 pain score ranging from zero "no pain" to 10 "worst possible pain". Week 3 analysis was defined as the mean of the last seven days in the study. The last day was taken as the last day with complete diary card pain data that occurred on or before the last day the patient took study medication. A negative value from baseline indicates and improvement.
Measured: 0 - 3 weeks
Secondary outcomes (14)
Use of Analgesic Escape Medication.
The percentage of days on treatment on which escape medication was used is presented.
Measured: 0 - 3 weeks
Change From Baseline in Mean Sleep Disturbance Score at 3 Weeks.
Each day patients were asked to record in their patient diary, whether or not they were woken due to pain the previous night. Answers were recorded as "No", "Once", "Twice", "More than twice" and "Awake most of the night"; these were converted to a five point scale, zero to four, respectively. Sleep disturbance was summarised and analysed in the same manner as the analysis of the primary efficacy parameter of Box Scale-11 pain score. A negative value from baseline indicates and improvement.
Measured: 0 - 3 weeks
Change From Baseline in Mean Total Pain Disability Index Score at 3 Weeks.
The index consists of seven assessments of pain (representing different aspects) with each assessment scored on a zero "no disability" to 10 "total disability" scale. The total Pain Disability Index was calculated as the un-weighted sum of the seven pain scores; if one or more of the pain scores were missing then the total Pain Disability Index was set to missing. A reduction in score from baseline indicates and improvement.
Measured: 0 - 3 weeks
Change From Baseline in Mean Total Brief Pain Inventory (Short Form) Score at 3 Weeks.
The Brief Pain Inventory (Short Form) 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 reduction in score from baseline indicates an improvement.
Measured: 0 - 3 weeks
Change From Baseline in Mean Spitzer Quality of Life Index Scores at 3 Weeks.
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 was required to choose the one that best described their quality of life during the last week. Choice 1 is scored two, Choice 2 is scored one and Choice 3 is scored zero. The total Spitzer Quality of Life Index was calculated as the unweighted sum of the five scores. A reduction in score from baseline indicates an improvement.
Measured: 0 - 3 weeks
Patient Global Impression of Change at the End of 3 Weeks of Treatment.
The Patient Global Impression of Change consisted of a single question relating to improvement in overall condition since the start of the study. The results were recorded as "Very Much Improved", "Much Improved", "Minimally Improved", "No Change", "Minimally Worse", "Much Worse" and "Very Much Worse" and were converted to a seven point scale ranging from one to seven, respectively. The number of patients who reported being "Very Much Improved" or "Much Improved" is presented.
Measured: 0 - 3 weeks
Change From Baseline in Mean Pain Box Scale-11 Scores (Multiple Sclerosis Subset) at 3 Weeks.
Each day, in the morning (on waking), at lunchtime and in the evening (just before going to bed), patients recorded in their patient diary their level of pain using a Box Scale-11 pain score ranging from zero "no pain" to 10 "worst possible pain". Week 3 analysis was defined as the mean of the last seven days in the study. The last day was taken as the last day with complete diary card pain data that occurred on or before the last day the patient took study medication. A negative value from baseline indicates and improvement.
Measured: 0 - 3 weeks
Use of Analgesic Escape Medication - Multiple Sclerosis Subset.
The percentage of days on treatment on which escape medication was used is presented.
Measured: 0 - 3 weeks
Change From Baseline in Mean Sleep Disturbance Scores (Multiple Sclerosis Subset) at 3 Weeks.
Each day patients were asked to record in their patient diary, whether or not they were woken due to pain the previous night. Answers were recorded as "No", "Once", "Twice", "More than twice" and "Awake most of the night"; these were converted to a five point scale, zero to four, respectively. Sleep disturbance was summarised and analysed in the same manner as the analysis of the primary efficacy parameter of Box Scale-11 pain score. A negative value from baseline indicates and improvement.
Measured: 0 - 3 weeks
Change From Baseline in Mean Pain Disability Index Scores at 3 Weeks.
The index consists of seven assessments of pain (representing different aspects) with each assessment scored on a zero "no disability" to 10 "total disability" scale. The total Pain Disability Index was calculated as the un-weighted sum of the seven pain scores; if one or more of the pain scores were missing then the total Pain Disability Index was set to missing. A reduction in score from baseline indicates and improvement.
Measured: 0 - 3 weeks
Change From Baseline in Mean Brief Pain Inventory (Short Form) Scores (Multiple Sclerosis Subset) at 3 Weeks.
The Brief Pain Inventory (Short Form) 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 reduction in score from baseline indicates an improvement.
Measured: 0 - 3 weeks
Change From Baseline in Mean Spitzer Quality of Life Index Scores (Multiple Sclerosis Subset) at 3 Weeks.
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 was required to choose the one that best described their quality of life during the last week. Choice 1 is scored two, Choice 2 is scored one and Choice 3 is scored zero. The total Spitzer Quality of Life Index was calculated as the unweighted sum of the five scores. A reduction in score from baseline indicates an improvement.
Measured: 0 - 3 weeks
Patient Global Impression of Change - Multiple Sclerosis Subset.
The Patient Global Impression of Change consisted of a single question relating to improvement in overall condition since the start of the study. The results were recorded as "Very Much Improved", "Much Improved", "Minimally Improved", "No Change", "Minimally Worse", "Much Worse" and "Very Much Worse" and were converted to a seven point scale ranging from one to seven, respectively. The number of patients who reported being "Very Much Improved" or "Much Improved" is presented.
Measured: 0 - 3 weeks
Incidence of Adverse Events as a Measure of Patient Safety.
The number of patients who experienced an adverse event in the study is presented.
Measured: 0 - 65 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 startMar 2002
- Primary completionAug 2002
- Study completionAug 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.
- 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
- 70 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
- NCT01606176
- Sponsor's protocol ID
- GWPS0105
- 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
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 Multi Centre Randomised, Double Blind, Placebo Controlled, Parallel Group Comparison of the Effects of Cannabis Based Medicine Standardised Extracts Over 4 Weeks, in Patients With Chronic Refractory Pain Due to Multiple Sclerosis or Other Defects of Neurological Function.
- ClinicalTrials.gov ID
- NCT01606176
- Acronym / sponsor ID
- GWPS0105
- Conditions
- Pain, Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Mar 2002
- Primary completion
- Aug 2002 (actual)
- Study completion
- Aug 2002 (actual)
- First posted
- 25 May 2012 (estimated)
- Results
- Posted 24 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the ability of a cannabis based medicine extract to relieve chronic refractory pain of neurological origin.
Detailed description
Patients with Multiple Sclerosis or other defect of neurological function with a qualifying symptom of chronic refractory pain, entered a seven day baseline period, followed by a 21 day randomised, double blind, parallel group comparison of GW-1000-02 with placebo, self-titrated to symptom resolution or maximum tolerated dose. The ability of the cannabis based medicine extract to relieve chronic refractory pain was assessed by the change from baseline in pain score using Box Scale-11 (BS-11) scores recorded in the patients' daily diary.
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-1000-02Each 100 μl actuation contains 2.5 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). The maximum permitted dose was 48 actuations in any 24 hour period (120 mg THC/120 mg CBD). |
| Placebo | Placebo comparator | Drug: PlaceboEach 100 μl actuation contains the excipients only. The maximum permitted dose was 48 actuations in any 24 hour period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patient, or legal representative, willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Diagnosed with chronic refractory pain due to Multiple Sclerosis or other defects of neurological function.
- Diagnosed with pain, not wholly alleviated with current analgesic therapy at Visit 1 and an average score of over 4 on a Box Scale-11 scale on the four consecutive days leading up to Visit 2, where: zero = "no pain" and 10 = "worst possible pain".
- Stable dose of pain relieving medication for at least two weeks prior to study entry.
Key exclusion criteria (17 listed)
- History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- Known 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 epilepsy.
- Female patients who were pregnant, lactating or planning pregnancy during the course of the study.
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: SativexEach actuation of GW-1000-02 (100 μl) delivered a dose containing 2.5 mg delta-9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD). The maximum permitted dose of study medication was eight actuations in any three hour period (20 mg THC/20 mg CBD) and 48 actuations in any 24 hour period (120 mg THC/120 mg CBD). | Drug | GW-1000-02 |
| PlaceboEach actuation of placebo (100 μl) delivered the excipients only. 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 Pain Box Scale-11 Score at 3 Weeks.
Time frame: 0 - 3 weeks
Each day, in the morning (on waking), at lunchtime and in the evening (just before going to bed), patients recorded in their patient diary their level of pain using a Box Scale-11 pain score ranging from zero "no pain" to 10 "worst possible pain". Week 3 analysis was defined as the mean of the last seven days in the study. The last day was taken as the last day with complete diary card pain data that occurred on or before the last day the patient took study medication. A negative value from baseline indicates and improvement.
14 secondary outcomes
Use of Analgesic Escape Medication.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Sleep Disturbance Score at 3 Weeks.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Total Pain Disability Index Score at 3 Weeks.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Total Brief Pain Inventory (Short Form) Score at 3 Weeks.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Spitzer Quality of Life Index Scores at 3 Weeks.
Time frame: 0 - 3 weeks
Patient Global Impression of Change at the End of 3 Weeks of Treatment.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Pain Box Scale-11 Scores (Multiple Sclerosis Subset) at 3 Weeks.
Time frame: 0 - 3 weeks
Use of Analgesic Escape Medication - Multiple Sclerosis Subset.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Sleep Disturbance Scores (Multiple Sclerosis Subset) at 3 Weeks.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Pain Disability Index Scores at 3 Weeks.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Brief Pain Inventory (Short Form) Scores (Multiple Sclerosis Subset) at 3 Weeks.
Time frame: 0 - 3 weeks
Change From Baseline in Mean Spitzer Quality of Life Index Scores (Multiple Sclerosis Subset) at 3 Weeks.
Time frame: 0 - 3 weeks
Patient Global Impression of Change - Multiple Sclerosis Subset.
Time frame: 0 - 3 weeks
Incidence of Adverse Events as a Measure of Patient Safety.
Time frame: 0 - 65 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.
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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 and 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 10 inclusion and 17 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 24 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 Pain Box Scale-11 Score at 3 Weeks. (time frame: 0 - 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.