Back to resultsA Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
Primary Purpose
Pain, Peripheral Neuropathy
Status
Completed
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Sativex
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Pain focused on measuring Pain, Peripheral Neuropathy, Allodynia
Eligibility Criteria
Inclusion Criteria:
- 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 PNP of at least six months duration and in who pain is not wholly relieved with their current therapy.
- Presence of mechanical allodynia within the territory of the affected nerve(s) which has been confirmed by either a positive response to stroking the allodynic area with a SENSELABTM Brush 05 or to force applied by a 5.07 gram Semmes-Weinstein monofilament.
- Had at least one of the following underlying conditions, which caused their peripheral neuropathic pain; post herpetic neuralgia, peripheral neuropathy, focal nerve lesion, radiculopathy or Complex Regional Pain Syndrome (CRPS) type 2.
- The daily diary 0-10 NRS pain scores on days B2 - B7 of the baseline period were completed and 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. Where subjects were taking a medication containing paracetamol further instructions were provided, refer to Section 9.4.7.
- In the opinion of the investigator the subject has received or was currently receiving the appropriate PNP treatments for their condition.
- 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.
Exclusion Criteria:
- Concomitant pain thought by the investigator to be of a nature or severity to interfere with the subject's assessment of their PNP.
- Receiving a prohibited medication and were unwilling to stop or comply for the duration of the study.
- Had CRPS type 1, cancer related neuropathic pain or neuropathic pain resulted from diabetes mellitus.
- Has used either cannabis (either for recreational or medical purposes) or cannabis based medications within the last year 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.
- 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 study medication.
- 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 unless physiological) or sinus tachycardia (HR>110bpm) at Visit 1.
- Diastolic blood pressure of <50 mmHg or >105 mmHg in a sitting position at rest for 5 minutes prior to randomisation.
- Impaired renal function i.e., creatinine clearance is lower than 50ml/min at Visit 1 and is indicative of renal impairment.
- 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 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.
Sites / Locations
- Pain Clinic Office, Gartnavel General Hospital,
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sativex
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in Mean Peripheral Neuropathic Pain on a 0-10 Numerical Rating Scale (NRS) Score at the End of Treatment (15 Weeks)
The peripheral neuropathic pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain 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. A negative value indicates an improvement in pain score from baseline.
Secondary Outcome Measures
Change From Baseline in Neuropathic Pain Scale Score at the End of Treatment (15 Weeks)
The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Change From Baseline in Sleep Quality 0-10 Numerical Rating Scale Scores at the End of Treatment (15 Weeks)
The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Change in Baseline Mean Dynamic Allodynia Test Score at the End of Treatment (15 Weeks)
Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5 s intervals, and recording the pain severity on a 0-10 point scale (0= no pain to 10 = most pain imaginable). All strokes were of the same length, minimum 2 cm. Each dynamic allodynia score was calculated as the average of the five strokes.A negative change from baseline indicates an improvement in score.
Change in Baseline Mean Punctate Allodynia Test Scores at the End of Treatment (15 Weeks)
Punctate allodynia was measured using an in-house built pressure algometer comprising a strain gauge connected to a metal filament with a diameter of 1 mm and blunt tip at baseline and end of study. The filament was manually directed against the skin at an angle of 90 degrees and a steadily increasing pressure applied until the patient verbally indicated that they perceived pain (punctate pressure pain threshold). Patients were asked to verbally rate the intensity of the pain elicited, choosing a number between 0 (no pain)and 10 (most intense pain imaginable).
Subject Global Impression of Change
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to peripheral neuropathy since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by peripheral neuropathy which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Change From Baseline in Brief Pain Inventory (Short Form) Scores at the End of Treatment
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Change From Baseline in Quality of Life EuroQol 5-D (Health Status Index) Score at the End of Treatment (15 Weeks)
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.
Change From Baseline in Quality of Life EuroQol 5-D (Health Status Visual Analogue Scale) Score at the End of Treatment (15 Weeks)
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.
Change From Baseline in the Use of Rescue Analgesia at the End Treatment (15 Weeks)
Use of break through medication was recorded daily during the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Incidence of Adverse Events as a Measure of Subject's Safety.
The number of subjects that reported an adverse event in this study is presented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00710554
Brief Title
A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
Official Title
A Double Blind, Randomized, Placebo Controlled, Parallel Group Study of Sativex® in the Treatment of Subjects With Peripheral Neuropathic Pain, Associated With Allodynia
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
October 2006 (Actual)
Study Completion Date
October 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jazz Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in relieving peripheral neuropathic pain associated with allodynia.
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 PNP, associated with allodynia. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Peripheral Neuropathy
Keywords
Pain, Peripheral Neuropathy, Allodynia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
246 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sativex
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Sativex
Other Intervention Name(s)
GW-1000-02
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
GW-4001-01
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Peripheral Neuropathic Pain on a 0-10 Numerical Rating Scale (NRS) Score at the End of Treatment (15 Weeks)
Description
The peripheral neuropathic pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain 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. A negative value indicates an improvement in pain score from baseline.
Time Frame
Day 7 to Day 98
Secondary Outcome Measure Information:
Title
Change From Baseline in Neuropathic Pain Scale Score at the End of Treatment (15 Weeks)
Description
The NPS score is 0-100 sum of 10 individual pain scores (0-10 NRS, 0= no pain to 10 = most pain imaginable). A negative change from baseline indicates an improvement in pain.
Time Frame
Day 7 to Day 98
Title
Change From Baseline in Sleep Quality 0-10 Numerical Rating Scale Scores at the End of Treatment (15 Weeks)
Description
The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Time Frame
Day 7 to Day 98
Title
Change in Baseline Mean Dynamic Allodynia Test Score at the End of Treatment (15 Weeks)
Description
Dynamic allodynia was assessed by stroking the skin over the affected area five times with a standardised brush, designed specifically for sensory testing at 5 s intervals, and recording the pain severity on a 0-10 point scale (0= no pain to 10 = most pain imaginable). All strokes were of the same length, minimum 2 cm. Each dynamic allodynia score was calculated as the average of the five strokes.A negative change from baseline indicates an improvement in score.
Time Frame
Day 7 and Day 98
Title
Change in Baseline Mean Punctate Allodynia Test Scores at the End of Treatment (15 Weeks)
Description
Punctate allodynia was measured using an in-house built pressure algometer comprising a strain gauge connected to a metal filament with a diameter of 1 mm and blunt tip at baseline and end of study. The filament was manually directed against the skin at an angle of 90 degrees and a steadily increasing pressure applied until the patient verbally indicated that they perceived pain (punctate pressure pain threshold). Patients were asked to verbally rate the intensity of the pain elicited, choosing a number between 0 (no pain)and 10 (most intense pain imaginable).
Time Frame
Day 7 and Day 98
Title
Subject Global Impression of Change
Description
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to peripheral neuropathy since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by peripheral neuropathy which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Time Frame
Day 98
Title
Change From Baseline in Brief Pain Inventory (Short Form) Scores at the End of Treatment
Description
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Time Frame
Day 7 and Day 98
Title
Change From Baseline in Quality of Life EuroQol 5-D (Health Status Index) Score at the End of Treatment (15 Weeks)
Description
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.The weighted health state index used the same VAS as above but was calculated for each assessment without imputation to account for missing values i.e., if one or more individual items was missing then the whole index was missing.
Time Frame
Day 7 and Day 98
Title
Change From Baseline in Quality of Life EuroQol 5-D (Health Status Visual Analogue Scale) Score at the End of Treatment (15 Weeks)
Description
The EQ-5D questionnaire provided two outcomes:(1)A weighted health state index visual analogue scale (VAS); (2) A self-rated health status VAS. EQ-5D Health Status VAS Scale: 0 = worst health state imaginable to 100 = best health state imaginable. An increase in score indicates an improvement in condition.
Time Frame
Day 7 and Day 98
Title
Change From Baseline in the Use of Rescue Analgesia at the End Treatment (15 Weeks)
Description
Use of break through medication was recorded daily during the study as the number of paracetamol tablets taken. The change in mean daily quantities of tablets used was calculated from baseline to the last seven days of treatment.
Time Frame
Days 0-7 and Days 92-98
Title
Incidence of Adverse Events as a Measure of Subject's Safety.
Description
The number of subjects that reported an adverse event in this study is presented.
Time Frame
19 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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 PNP of at least six months duration and in who pain is not wholly relieved with their current therapy.
Presence of mechanical allodynia within the territory of the affected nerve(s) which has been confirmed by either a positive response to stroking the allodynic area with a SENSELABTM Brush 05 or to force applied by a 5.07 gram Semmes-Weinstein monofilament.
Had at least one of the following underlying conditions, which caused their peripheral neuropathic pain; post herpetic neuralgia, peripheral neuropathy, focal nerve lesion, radiculopathy or Complex Regional Pain Syndrome (CRPS) type 2.
The daily diary 0-10 NRS pain scores on days B2 - B7 of the baseline period were completed and 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. Where subjects were taking a medication containing paracetamol further instructions were provided, refer to Section 9.4.7.
In the opinion of the investigator the subject has received or was currently receiving the appropriate PNP treatments for their condition.
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.
Exclusion Criteria:
Concomitant pain thought by the investigator to be of a nature or severity to interfere with the subject's assessment of their PNP.
Receiving a prohibited medication and were unwilling to stop or comply for the duration of the study.
Had CRPS type 1, cancer related neuropathic pain or neuropathic pain resulted from diabetes mellitus.
Has used either cannabis (either for recreational or medical purposes) or cannabis based medications within the last year 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.
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 study medication.
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 unless physiological) or sinus tachycardia (HR>110bpm) at Visit 1.
Diastolic blood pressure of <50 mmHg or >105 mmHg in a sitting position at rest for 5 minutes prior to randomisation.
Impaired renal function i.e., creatinine clearance is lower than 50ml/min at Visit 1 and is indicative of renal impairment.
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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mick Serpell, MB ChB, FRCA
Organizational Affiliation
Pain Clinic Office
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pain Clinic Office, Gartnavel General Hospital,
City
Glasgow
State/Province
West Lothain
ZIP/Postal Code
G12 0YN
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
24420962
Citation
Serpell M, Ratcliffe S, Hovorka J, Schofield M, Taylor L, Lauder H, Ehler E. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014 Aug;18(7):999-1012. doi: 10.1002/j.1532-2149.2013.00445.x. Epub 2014 Jan 13.
Results Reference
result
Learn more about this trial
A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
We'll reach out to this number within 24 hrs