PainPhase 3NCT00710424
A Study of Sativex® for Pain Relief Due to Diabetic Neuropathy
A Phase 3 study testing Sativex in people with Pain and Diabetic Neuropathy, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving pain due to Diabetic Neuropathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Diabetic Neuropathy
- What is being tested?
- Sativex
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 297 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2005to Jun 2006
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to give informed consent.
- Male or female, aged 18 years or above.
- Ability (in the investigators opinion) and willingness to comply with all study requirements.
- Diagnosed with Type 1 or 2 diabetes mellitus as diagnosed according to the World Health Organisation (WHO) criteria.
- Diagnosed with neuropathic pain due to distal symmetrical diabetic neuropathy of at least six months duration, as defined by a NDS score of at least 4, and in who pain is not wholly relieved with their current therapy. The NDS score must be attained from at least two different test parameters and not only the ankle jerk reflex.
- The last six daily diary 0-10 NRS pain scores before randomisation summed to at least 24.
- Stable dose of regular pain medication and non-pharmacological therapies (including TENS) for at least 14 days prior to the screening visit and willingness for these to be maintained throughout the study.
- Agreement for the responsible authorities (as applicable in individual countries), their primary care physician, and their consultant, if appropriate, to be notified of their participation in the study.
Who cannot join
- Concomitant pain thought by the investigator to be of a nature or severity to interfere with their assessment of their painful diabetic neuropathy.
- Uncontrolled diabetes with HbA1c blood levels of more than 11% at Visit1, Day B1.
- Receiving a prohibited medication and were unwilling to stop or comply for the duration of the study.
- Has used cannabinoid based medications within 60 days of study entry and were unwilling to abstain for the duration for the study.
- Has used cannabis within 30 days of study entry and were unwilling to abstain for the duration for the study.
- History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
Show all 26Show fewer
- Known or suspected history of alcohol or substance abuse.
- History of epilepsy or recurrent seizures.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP.
- Postural drop of 20mmHg or more in systolic blood pressure at screening.
- Medical history of gastroparesis.
- Evidence of cardiomyopathy.
- Experienced myocardial infarction or clinically relevant cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction.
- QT interval; of > 450 ms (males) or > 470 ms (females) at Visit 1.
- Secondary or tertiary AV block or sinus bradycardia (HR <50bpm) or sinus tachycardia (HR>110bpm) at Visit 1.
- Diastolic blood pressure of <50 mmHg or >105 mmHg in a sitting position at rest for five minutes prior to randomisation.
- Impaired renal function i.e., creatinine clearance is lower than 50 ml/min at Visit 1.
- Significantly impaired hepatic function, at Visit 1, in the investigator's opinion.
- Female subjects of child bearing potential and male subjects whose partner was of child bearing potential, unless they were willing to ensure that they or their partner used effective contraception during the study and for three months thereafter.
- If female, were pregnant or lactating, or were planning pregnancy during the course of the study and for three months thereafter.
- Received an IMP within the 12 weeks before Visit 1.
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, may influence the result of the study, or the subject's ability to participate in the study.
- Following a physical exam, the subject had any abnormalities that, in the opinion of the investigator, would prevent the subject from safely participating in the study.
- Intention to donate blood during the study.
- Intention to travel internationally during the study.
- Previous randomisation into this study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Hallamshire Hospital
Sheffield, Yorkshire, S10 2JF
About this study
Official title: A Double Blind, Randomized, Placebo Controlled, Parallel Group Study of Sativex in the Treatment of Subjects With Pain Due to Diabetic Neuropathy
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving pain due to Diabetic Neuropathy.
Read the detailed description
This was a 15 week (one week baseline and fourteen weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex in subjects with pain due to diabetic neuropathy. Subjects were screened to determine eligibility and completed a seven-day baseline period. Subjects then returned to the centre for assessment, randomisation and dose introduction. Visits occurred at the end of weeks two, six, ten and at the end of the study (treatment week 14) or earlier if they withdrew. A follow up visit occurred 28 days after completion or withdrawal. Subjects in this study were given the opportunity to be enrolled in an open label extension study.
- Conditions
- Pain, Diabetic Neuropathy
- Being tested
- Sativex, Placebo
- Keywords
- Pain, diabetic neuropathy
- Medical subject headings
- Pain, Diabetic Neuropathies
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 THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours
PlaceboDrug
Also called GW-4001-01
containing 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.
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Experimental | Not described Receives: Drug: Sativex |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Change From Baseline in Mean Diabetic Neuropathy Pain 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment)
The diabetic neuropathy pain Numerical Rating Scale was complete at the end of every day. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your nerve pain due to diabetes in the last 24 hours" where 0 = no pain and 10 = worst possible pain. No pain relates to the time prior to the onset of pain due to diabetic neuropathy. For those whose evaluable period ended before Day 7, the mean of the available post-randomisation data was used. Those with no post-baseline diary pain 0-10 Numerical Rating Scale scores were excluded from the analysis.
Measured: Day 0 to Day 98
Number of Responders at the 30% Improvement Level at the End of Treatment
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average 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 or average 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. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening. Estimates were produced for a one-week period, with the evaluable period finishing at the end of the appropriate seven-day period.
Measured: Day 0 - Day 98
Secondary outcomes (8)
Change From Baseline in Mean Neuropathic Pain Scale Score at the End of Treatment
The Neuropathic Pain Scale score is the 0-100 sum of 10 individual pain scores (0-10 Numerical Rating Scale, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain. The baseline mean Neuropathic Pain Scale score was to be the mean of the two assessments during the baseline period, with the end of study value as the mean of the last two assessments made during the evaluable period.
Measured: Day 0 to Day 98
Change From Baseline in Mean Sleep Quality 0-10 Numerical Rating Scale Score at the End of Treatment
The sleep quality Numerical Rating Scale 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 sleep quality in the last 24 hours" where 0 = slept extremely well and 10 = unable to sleep at all. A negative value indicates an improvement in pain score from baseline. The analyses were based on the change from baseline for the last assessment falling within the evaluable period (considered the end of treatment).
Measured: Day 0 - Day 98
Subject Global Impression of Change at the End of Treatment
The subject was to assess the change in their nerve pain due to diabetic neuropathy at the end of the study compared to baseline on a 7-point scale from very much worse to very much improved. The number of participants reporting each score is presented.
Measured: Day 0 and Day 98
Change From Baseline in Mean Brief Pain Inventory (Short Form)'Pain Severity Composite Score' at the End of Treatment
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 pain 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: Day 0 and Day 98
Change From Baseline in Mean Quality of Life EuroQol 5-D Weighted Health State Index Score at the End of Treatment Measured by Visual Analogue Scale
The EuroQol-5D Health Status Visual Analogue Scale rated the health state on a scale of 0-100 with 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.
Measured: Day 0 and Day 98
Change From Baseline in the Use of Rescue Analgesia at the End of Treatment
The mean daily number of paracetamol tablets used were calculated for the periods over which the primary endpoint was calculated.
Measured: Day 0 - Day 98
Incidence of Adverse Events as a Measure of Subject Safety
The number of subjects who experienced an adverse event during the course of the study (including the follow-up period i.e 28 days after the end of treatment) is presented.
Measured: Day 0 - Day 133
Change From Baseline in Mean Intoxication 0-10 Numerical Rating Scale Score at the End of Treatment
Subjects rated their intoxication levels on a scale of 0-10, where 0 equals "no intoxication" and 10 equals "extreme intoxication". A negaitve value from baseline indicates and improvement. End of treatment was classed as the last on-treatment visit where data was recorded.
Measured: Day 0 - Day 98
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2008 (estimated)
- Study startJul 2005
- Primary completionJun 2006
- Study completionJun 2006
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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 297 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Solomon Tesfaye, JCHMT FRCP, Principal investigator, Royal Hallamshire Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00710424
- Sponsor's protocol ID
- GWCL0305
- Status last verified
- Apr 2023
- First submitted
- 2 Jul 2008
- Last updated
- 3 May 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 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomized, Placebo Controlled, Parallel Group Study of Sativex in the Treatment of Subjects With Pain Due to Diabetic Neuropathy
- ClinicalTrials.gov ID
- NCT00710424
- Acronym / sponsor ID
- GWCL0305
- Conditions
- Pain, Diabetic Neuropathy
- Keywords
- Pain, diabetic neuropathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 297 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2005
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jun 2006 (actual)
- First posted
- 4 Jul 2008 (estimated)
- Results
- Posted 31 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving pain due to Diabetic Neuropathy.
Detailed description
This was a 15 week (one week baseline and fourteen weeks treatment period), multicentre, double blind, randomised, placebo controlled, parallel group study to evaluate the efficacy of Sativex in subjects with pain due to diabetic neuropathy. Subjects were screened to determine eligibility and completed a seven-day baseline period. Subjects then returned to the centre for assessment, randomisation and dose introduction. Visits occurred at the end of weeks two, six, ten and at the end of the study (treatment week 14) or earlier if they withdrew. A follow up visit occurred 28 days after completion or withdrawal. Subjects in this study were given the opportunity to be enrolled in an open label extension study.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sativex | Experimental | Drug: Sativex |
| Placebo | 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 (8 listed)
- Willing and able to give informed consent.
- Male or female, aged 18 years or above.
- Ability (in the investigators opinion) and willingness to comply with all study requirements.
- Diagnosed with Type 1 or 2 diabetes mellitus as diagnosed according to the World Health Organisation (WHO) criteria.
- Diagnosed with neuropathic pain due to distal symmetrical diabetic neuropathy of at least six months duration, as defined by a NDS score of at least 4, and in who pain is not wholly relieved with their current therapy. The NDS score must be attained from at least two different test parameters and not only the ankle jerk reflex.
Key exclusion criteria (26 listed)
- Concomitant pain thought by the investigator to be of a nature or severity to interfere with their assessment of their painful diabetic neuropathy.
- Uncontrolled diabetes with HbA1c blood levels of more than 11% at Visit1, Day B1.
- Receiving a prohibited medication and were unwilling to stop or comply for the duration of the study.
- Has used cannabinoid based medications within 60 days of study entry and were unwilling to abstain for the duration for the study.
- Has used cannabis within 30 days of study entry and were unwilling to abstain for the duration for 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 |
|---|---|---|
| SativexAlso: GW-1000-02containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours | Drug | Sativex |
| PlaceboAlso: GW-4001-01containing 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. | Drug | Placebo |
Primary outcome
The Change From Baseline in Mean Diabetic Neuropathy Pain 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment)
Time frame: Day 0 to Day 98
The diabetic neuropathy pain Numerical Rating Scale was complete at the end of every day. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your nerve pain due to diabetes in the last 24 hours" where 0 = no pain and 10 = worst possible pain. No pain relates to the time prior to the onset of pain due to diabetic neuropathy. For those whose evaluable period ended before Day 7, the mean of the available post-randomisation data was used. Those with no post-baseline diary pain 0-10 Numerical Rating Scale scores were excluded from the analysis.
Number of Responders at the 30% Improvement Level at the End of Treatment
Time frame: Day 0 - Day 98
A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average 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 or average 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. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening. Estimates were produced for a one-week period, with the evaluable period finishing at the end of the appropriate seven-day period.
8 secondary outcomes
Change From Baseline in Mean Neuropathic Pain Scale Score at the End of Treatment
Time frame: Day 0 to Day 98
Change From Baseline in Mean Sleep Quality 0-10 Numerical Rating Scale Score at the End of Treatment
Time frame: Day 0 - Day 98
Subject Global Impression of Change at the End of Treatment
Time frame: Day 0 and Day 98
Change From Baseline in Mean Brief Pain Inventory (Short Form)'Pain Severity Composite Score' at the End of Treatment
Time frame: Day 0 and Day 98
Change From Baseline in Mean Quality of Life EuroQol 5-D Weighted Health State Index Score at the End of Treatment Measured by Visual Analogue Scale
Time frame: Day 0 and Day 98
Change From Baseline in the Use of Rescue Analgesia at the End of Treatment
Time frame: Day 0 - Day 98
Incidence of Adverse Events as a Measure of Subject Safety
Time frame: Day 0 - Day 133
Change From Baseline in Mean Intoxication 0-10 Numerical Rating Scale Score at the End of Treatment
Time frame: Day 0 - Day 98
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Solomon Tesfaye, JCHMT FRCP principal investigator
Royal Hallamshire Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sativex in people with Pain and Diabetic Neuropathy, 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 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 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?
The Change From Baseline in Mean Diabetic Neuropathy Pain 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment) (time frame: Day 0 to Day 98). 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?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.