The purpose of this study is to assess the safety and tolerability of long term therapy with Sativex® in relieving neuropathic pain.
This was a 38 week, multicentre, open label (Part A) follow-on study to evaluate, the maintenance of effect of, the development of tolerance through exposure to, and safety of, Sativex® in the treatment of subjects with neuropathic pain. The study provided continued availability of Sativex® to subjects who completed the preceding double-blind neuropathic pain studies. Consenting, eligible subjects who had participated in previous GW Pharma Ltd (GW) randomised, placebo-controlled clinical studies entered the study (Visit 1, Day 0) and commenced dosing. Study visits took place at Week 2 (Visit 2, Day 14), Week 14 (Visit 3, Day 98), and Week 26 (Visit 4, Day 182). Subjects returned to the centre for an end of treatment visit at week 38 (Visit 5, Day 266). All subjects received Sativex®. This was followed by a five week randomised-withdrawal phase (Part B) for a subset of subjects. An end of study visit took place 28 days after Visit 5 (or 5b or 5c) or withdrawal from the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
380
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
Pain Management Research, Clinical Trials Unit, Netherwood House, Solihull Hospital
Solihull, West Midlands, United Kingdom
Change From Parent Study Baseline in Mean Pain 0-10 Numerical Rating Scale (NRS) Score During the Last 4 Weeks of Open-label Treatment
The average pain NRS was complete 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: 38 weeks
Change From Parent Study Baseline in Mean Neuropathic Pain Scale (NPS) Score at End of Open-label Treatment (Week 38)
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: 38 weeks
Change From Parent Study Baseline in Mean Sleep Quality 0-10 NRS Score at the End of Open-label Treatment (Week 38)
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: 38 weeks
Subject Global Impression of Change
A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain 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 which was used at Week 5 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
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Time frame: week 38
Change From Parent Study Baseline in Mean EuroQol-5D Weighted Health State Index Score at the End of Open-label Treatment
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: 38 weeks
Change From Parent Study Baseline in Mean EuroQol-5D Self-rated Health Status Visual Analogue Scale Score at the End of Open-label Treatment
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: 38 weeks
Incidence of Adverse Events as a Measure of Subject Safety
The number of subjects who reported an adverse event during Part A of the study is presented (including the follow-up period of 28 days following cessation of opel-label treatment).
Time frame: 42 weeks
Change From Parent Study Baseline in Mean Intoxication 0-10 Numerical Rating Scale Score at the End of Open-label Treatment (38 Weeks)
The patient was asked "on a scale of '0 to 10' please indicate the average level of your intoxication due to medications over the last 24 hours" (0=no intoxication and 10=extreme toxication). A negative value indicates an improvement in pain score from baseline.
Time frame: 38 weeks