Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer (SPRAY III)

• Change from baseline in mean NRS average pain [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
• Change from baseline in mean NRS worst pain [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
• Change from baseline in mean Sleep Disruption NRS [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]

This 9-week study aimed to determine the efficacy, safety and tolerability of Sativex® (Nabiximols) as an adjunctive treatment, compared with placebo in relieving uncontrolled persistent chronic pain in patients with advanced cancer.

Eligible patients were not required to stop any of their current treatments or medications.

This 9-week, multi-center, double-blind, randomized, placebo-controlled study aimed to determine the efficacy, safety and tolerability of Sativex administered as an adjunctive treatment for 5 weeks, vs. placebo. Eligible patients had advanced cancer, with a clinical diagnosis of cancer related pain which was not wholly alleviated by their current optimized opioid treatment.

Qualifying patients entered the study at Visit 1 and commenced a 5-14 day eligibility period. During this period, eligible patients had 3 consecutive days where pain severity remained within defined parameters, break-through opioid usage had not exceeded an average of 4 episodes per day, and maintenance opioid medication and dose had not changed. Eligible patients returned for a randomization visit (Visit 2, Day 1) and were randomized to either Sativex or placebo using a 1:1 allocation ratio. Patients began an initial titration period lasting up to 14 days; the titration schedule required dosing to a minimum of 3 sprays per day, after which patients were allowed to individualize their dose (3-10 sprays per day) by Day 14, and that dose was then fixed for the remainder of the study. Patients returned at Visit 3 (Day 22) and Visit 4 (Day 36, end of the randomized treatment period), or earlier if they terminated prematurely from the study. After the end of the 5-week treatment period, patients were offered the option of entering an open-label extension (OLE) study; a safety follow up visit (Visit 5) was not required if the patient entered the OLE on the same day as Visit 4. Patients who entered the OLE up to 7 days after Visit 4 had their Visit 5 assessments performed on the same day as their first OLE study visit. Patients that did not enter the OLE study had a safety follow up visit (Visit 5) 14 days after treatment completion, which could be via telephone.

• Pain
• Advanced Cancer

• Drug: Sativex®
  Other Name: Nabiximols
• Drug: Placebo (GA-0034)

• Placebo Comparator: Placebo (GA-0034)
  Placebo oromucosal spray. 100 μl administered twice daily up to a maximum of 10 sprays per day.
  Intervention: Drug: Placebo (GA-0034)
• Experimental: Sativex®
  Sativex oromucosal spray. 100 μl administered twice daily up to a maximum of 10 sprays per day.
  Intervention: Drug: Sativex®

Inclusion Criteria (abbreviated):

• The patient has advanced cancer for which there is no known curative therapy
• The patient has a clinical diagnosis of cancer related pain, which is not alleviated with their current optimized opioid treatment
• The patient is receiving an optimized maintenance dose of Step III opioid therapy, preferably with a sustained release preparation, but also allowing a regular maintenance dose of around the clock use of immediate release preparations
• The patient is receiving a daily maintenance dose Step III opioid therapy of less than or equal to a total daily opioid dose of 500 mg/day of morphine equivalence (including maintenance and break-through opioids)
• The patient is using no more than one type of break-through opioid analgesia

Exclusion Criteria (abbreviated):

• Have any planned clinical interventions that would affect their pain (e.g., chemotherapy or radiation therapy where, in the clinical judgment of the investigator, these would be expected to affect pain)
• The patient is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is unwilling to abstain for the duration of the study
• Has experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of a clinically significant arrhythmia or myocardial infarction
• Has significantly impaired renal function
• Has significantly impaired hepatic function
• Female patients of child-bearing potential and male patients whose partner is of child-bearing potential, unless willing to ensure that they or their partner use effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (however, a male condom should not be used in conjunction with a female condom as this may not prove effective)