Sativex® for Relieving Persistent Pain in Patients With Advanced Cancer

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

Qualifying participants entered the study at screening and commenced a 5 to 14 day
eligibility period. During this period, eligible participants 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 participants returned for randomization on Day 1 and were randomized to either the
nabiximols or placebo treatment arm using a 1:1 allocation ratio. Participants began an
initial titration period that lasted up to 14 days. The titration schedule required dosing to
a minimum of 3 sprays per day, after which participants were allowed to individualize their
dose (3 to 10 sprays per day) until Day 14 when that dose was then fixed for the remainder of
the study. Participants returned at Day 22 and 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, participants were offered the option of entering an open-label
extension (OLE) study; a safety follow up visit (up to Day 43) was not required if the
participant entered the OLE on Day 36. Participants who entered the OLE, up to 7 days after
study completion had their follow-up assessments performed on the same day as their first OLE
study visit. Participants that did not enter the OLE study had a safety follow up visit 14
days after treatment completion, which could be via telephone.

Inclusion Criteria (abbreviated):

- The participant had advanced cancer for which there was no known curative therapy

- The participant had a clinical diagnosis of cancer related pain, which was not wholly
alleviated with their current optimized opioid treatment

- The participant received an optimized maintenance dose of Step 3 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 participant received a daily maintenance dose Step 3 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 participant was using no more than one type of break-through opioid analgesia

Exclusion Criteria (abbreviated):

- The participant had any planned clinical interventions that would have affected their
pain (for example, chemotherapy or radiation therapy where, in the clinical judgment
of the investigator, these would be expected to affect pain)

- The participant was using or had used cannabis or cannabinoid-based medications within
30 days of study entry and is unwilling to abstain for the duration of the study

- The participant had experienced myocardial infarction or clinically significant
cardiac dysfunction within the last 12 months or had a cardiac disorder that, in the
opinion of the investigator, would have put the participant at risk of a clinically
significant arrhythmia or myocardial infarction

- The participant had significantly impaired renal function

- The participant had significantly impaired hepatic function

- Female participants of child-bearing potential and male participants whose partner was
of child-bearing potential, unless willing to ensure that they or their partner used
effective contraception, for example, oral contraception, double barrier,
intra-uterine device, during the study and for 3 months thereafter (however, a male
condom was not to be used in conjunction with a female condom as this may not have
proven effective)