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

• Change From Baseline Neuropathic Pain Score at the End of Treatment [ Time Frame: Day 7 to 35 ] [ Designated as safety issue: No ]
  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.
• Number of Subjects Who Failed Treatment at the End of the Treatment Period [ Time Frame: Day 7 to time of last dose ] [ Designated as safety issue: No ]

  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.

• Number of Subjects With More Than a 20% Loss of Response at the End of Treatment [ Time Frame: Day 0-35 ] [ Designated as safety issue: No ]
  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.
• Change From Baseline in Sleep Disruption 0-10 Numerical Rating Scale Score at the End of Treatment (Average of Last 7 Days Treatment) [ Time Frame: Day 0-35 ] [ Designated as safety issue: No ]
  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.
• Subject Global Impression of Change at the End of Treatment [ Time Frame: Day 7 to 35 ] [ Designated as safety issue: No ]
  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.
• Incidence of Adverse Events as a Measure of Subject Safety [ Time Frame: Day 0 -35 ] [ Designated as safety issue: Yes ]
  The number of subjects who experienced an adverse event during the course of the study is presented.

• Neuropathic Pain Score [ Time Frame: Days 0, 7 and 35 ] [ Designated as safety issue: No ]
• Time to Treatment Failure [ Time Frame: Day 7 to time of last dose ] [ Designated as safety issue: No ]
• Loss of Response [ Time Frame: Day 0-35 ] [ Designated as safety issue: No ]
• Sleep disruption [ Time Frame: Day 0-35 ] [ Designated as safety issue: No ]
• subject global impression of change [ Time Frame: Day 7 and 35 ] [ Designated as safety issue: No ]
• Adverse events [ Time Frame: Day 0 -35 ] [ Designated as safety issue: Yes ]
• Vital signs. [ Time Frame: Day 0 and 35 ] [ Designated as safety issue: Yes ]
• Oral Examination [ Time Frame: Day 0 and 35 ] [ Designated as safety issue: Yes ]

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

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.

• Pain
• Peripheral Neuropathy

• Drug: Sativex®
  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
  Other Name: GW-1000-02
• Drug: Placebo
  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
  Other Name: GW-4001-01

• Experimental: Sativex
  Intervention: Drug: Sativex®
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

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