A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain

Study Overview
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Brief Summary
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The purpose of this study is to assess the maintenance of effect after long-term treatment of Sativex® in subjects with neuropathic pain.

Detailed Description
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A five week randomised-withdrawal phase (Part B) for a subset of subjects who took part in 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. Subjects returned to the centre for an end of treatment visit at week 38 of Part A (Visit 5, Day 266), followed by Visits 5b (week 39), 5c (week 43) and an end of study visit took place 28 days after Visit 5c or withdrawal from the study.

Official Title
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A Multicentre, Open Label, Follow on Study to Assess the Maintenance of Effect, Tolerance and Safety of Sativex® in the Treatment of Subjects With Neuropathic Pain. This Will be Followed by a Randomised-withdrawal Phase (Part B) for a Subset of Patients

Conditions
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Pain, Peripheral Neuropathy

Intervention / Treatment
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* Drug: Sativex®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had participated in GWCL0404, was currently ongoing in the study (i.e. still receiving GW-1000-02 treatment) and had completed the study up to Visit 5 Had complied with all of the study requirements to-date, including the completion of the diary cards Had shown tolerability to the study medication in this study Ability (in the investigators opinion) and willingness to comply with all study requirements, including the completion of diary cards and study questionnaires Exclusion Criteria: Had experienced or was currently experiencing any adverse events or untoward medical occurrences which, in the opinion of the investigator, would prevent them from safely participating in this phase of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sativex<br> | Drug: Sativex®<br>* Containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours<br>* Other names: GW-1000-02;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 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<br>* Other names: GW-4001-01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Daily Pain Severity on a 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment) | The pain severity Numerical Rating Scale 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 severity 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 neuropathic pain. A negative value indicates an improvement in pain score from baseline. | Day 0-35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Neuropathic Pain 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. | Day 7 to 35 | 
| Number of Subjects Who Failed Treatment at the End of the Treatment Period | Treatment failure was defined as follows: A. Premature termination of Part B (Randomised-Withdrawal) study medication. All subjects who did not complete at least 28 days on Part B (Randomised-Withdrawal) study medicationOr: B. An increase in pain, i.e. the mean pain 0-10 Numerical Rating Scale over seven consecutive days after Part B (Randomised-Withdrawal) randomisation had increased by at least 20% from the Part B (Randomised-Withdrawal) randomised treatment baseline. | Day 7 to time of last dose | 
| Number of Subjects With More Than a 20% Loss of Response at the End of Treatment | The percentage change from baseline in mean 0-10 Numerical Rating Scale pain score was calculated. The percentage changes from baseline were classified and the number of subjects with 20% or greater loss of response to treatment (i.e. percent increase from baseline ≥ 20%) is presented. | Day 0-35 | 
| Change From Baseline in Sleep Disruption 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment) | The sleep disruption 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 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. | Day 0-35 | 
| Subject Global Impression of Change at the End of Treatment | A 7-point Likert-type scale was used, with the question: 'Please assess the status of your nerve 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. The number of subjects wo reported an improvement is presented. | Day 7 to 35 | 
| 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 is presented. | Day 0 -35 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Peripheral Neuropathy