A Two-part, Placebo-controlled, Study of the Safety and Efficacy of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Relieving Uncontrolled Persistent Chronic Pain in Patients With Advanced Cancer, Who Have Inadequate Analgesia Even With Optimized Chronic Opioid Therapy.

Time frame

Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEAN · units on a scale

Reporting status

POSTED

Participants indicated the level of pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: End of Treatment NRS average pain score - Randomization (Part B) Baseline NRS average pain score. The participant's Randomization (Part B) baseline pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in average pain score from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Eligibility Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEDIAN · percent improvement

Reporting status

POSTED

Participants indicated level of pain in the last 24 hours on an 11-point NRS, where a score of 0 was "no pain" and 10 was "pain as bad as you can imagine". Eligibility Baseline = mean score from the 3-day eligibility period. End of Treatment = mean score over last (up to) 4 days to the final pain score at End of Treatment or up until Day 36 of the double-blind period, whichever is earlier, or final score available (prematurely terminated). Percentage improvement from baseline (Imp%) was calculated as: Imp% = (Eligibility Baseline pain NRS mean - End of Treatment pain NRS mean)/Eligibility Baseline pain NRS mean \* 100. For participants who died or withdrew due to disease progression, Imp% values were used. For participants who died or withdrew unrelated to disease progression before end of Week 5, Imp% was zero for participants whose Imp% value was positive and it was Imp% for participants whose Imp% value was not positive.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEAN · units on a scale

Reporting status

POSTED

Participants indicated the level of worst pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS worst pain was calculated as: End of Treatment NRS worst pain score - Randomization (Part B) Baseline NRS worst pain score. The participant's Randomization (Part B) baseline worst pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in worst pain score from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEAN · units on a scale

Reporting status

POSTED

Participants indicated the level of sleep disruption experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "did not disrupt sleep" and a score of 10 indicated "completely disrupted (unable to sleep at all)." Change in mean sleep disruption NRS was calculated as: End of Treatment sleep disruption NRS score - Randomization (Part B) Baseline sleep disruption NRS score. The participant's Randomization (Part B) baseline sleep disruption 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in sleep disruption score from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Last Visit (up to Day 36 of the double-blind period)

Measure

COUNT_OF_PARTICIPANTS · Participants

Reporting status

POSTED

The Subject Global Impression of Change (SGIC) was used to assess the overall status of the participant related to their cancer pain, with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse". The SGIC was assessed at Day 36 of the double-blind period or the day at which a participant's last evaluation was performed, such as in the case of early termination. Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Last Visit (up to Day 36 of the double-blind period)

Measure

COUNT_OF_PARTICIPANTS · Participants

Reporting status

POSTED

The Physician Global Impression of Change (PGIC) was used by the treating physician (investigator/sub-investigator) to assess if there was any change in the general functional abilities of the participant since prior to commencement of study medication, with the markers: "very much worse, much worse, slightly worse, no change, slightly improved, much improved, very much improved". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Last Visit (up to Day 36 of the double-blind period)

Measure

COUNT_OF_PARTICIPANTS · Participants

Reporting status

POSTED

The Patient Satisfaction Questionnaire (PSQ) was used to assess level of satisfaction of the participant with the study drug, with the markers "extremely satisfied, very satisfied, slightly satisfied, neutral, slightly dissatisfied, very dissatisfied, extremely dissatisfied". Last visit refers to the last visit that a participant completed the assessment; this could be either Day 22 or Day 36 of the double-blind period.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEAN · mg (morphine equivalent)

Reporting status

POSTED

The total daily opioid use (in morphine equivalence) was the sum of morphine equivalence of daily maintenance dose and break-through dose. Change in daily total opioid use was calculated as: End of Treatment daily total opioid use - Randomization (Part B) Baseline daily total opioid use. The participant's Randomization (Part B) baseline daily total opioid use value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in use from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEAN · mg (morphine equivalent)

Reporting status

POSTED

The prescribed daily quantity of opioid maintenance dose was calculated as the product of dose per use and daily frequency of use. Participants were asked: "Have you used your maintenance dose painkiller today as prescribed?" If the participant answered "No" to the question, the daily opioid maintenance dose usage on that day was set to 0. Change in daily maintenance opioid dose was calculated as: End of Treatment daily maintenance opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily maintenance opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Randomization Baseline, End of Treatment (Day 36 of the double-blind period)

Measure

MEAN · mg (morphine equivalent)

Reporting status

POSTED

Daily break-through opioid dose usage was calculated as the product of prescribed dose per use, and the number of uses per day. If participants took more than 1 different break-through opioid for more than 1 day, the sum of morphine equivalence dose usages for each break-through opioid was calculated for the summary. Change in daily break-through opioid dose was calculated as: End of Treatment daily break-through opioid dose - Randomization (Part B) Baseline daily maintenance opioid dose. The participant's Randomization (Part B) baseline daily break-through opioid dose value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates a decrease in dose from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Time frame

Randomization Baseline, Last Visit (up to Day 36 of the double-blind period)

Measure

MEAN · units on a scale

Reporting status

POSTED

Participants indicated level of constipation on an 11-point NRS, where a score of 0 was "no constipation", and 10 was "constipation as bad as you can imagine." Last visit refers to the last visit that a participant completed the assessment. Change in NRS constipation score was calculated as: Last Visit NRS constipation score - Randomization (Part B) Baseline NRS constipation score. The participant's Randomization (Part B) baseline constipation NRS value was the last evaluation (including unscheduled visits) in the single-blind treatment period (Part A) prior to the first dose of study drug in the double-blind treatment period (Part B). A negative value indicates improvement in condition from Randomization (Part B) Baseline.

Population: The ITT Population included all participants who were randomized, received at least 1 dose of study drug, and had at least 1 efficacy endpoint. Participants were analyzed according to the treatment group they were randomized to.

Per the Statistical Analyses Plan, all randomized participants who received at least 1 dose of study drug were analyzed in the Intent to Treat (ITT) population as per randomized treatment group. Participants were included and analyzed according to the treatment group they were randomized to.