The Change in Mean Pain Numerical Rating Scale (NRS) Score From Baseline to the End of the Treatment.
The pain NRS 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 or average pain 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 pain due to cancer. A negative value indicates an improvement in pain score from baseline.
All subjects who were randomised, received at least one actuation of study medication and had on-treatment efficacy data were included in the ITT population. This population was used for the primary analysis. Presented below is the adjusted mean change from baseline in mean pain NRS.
Each 100 μl actuation of Sativex delivered a dose containing 2.7 mg THC and 2.5 mg CBD. The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations (130 mg THC and 120 mg CBD) in any 24 hour period.
Each 100 μl actuation of THC delivered a dose containing 2.7 mg THC only. The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations (130 mg) in any 24 hour period.
Each actuation of placebo delivered the excipients plus colourants. The maximum permitted dose of study medication was eight actuations in any three hour period, and 48 actuations in any 24 hour period.
The change in mean pain NRS score (average pain) was analyzed using analysis of covariance (ANCOVA) with the baseline value as a covariate and region and treatment group as factors. The null hypothesis was that of no treatment difference.
The Consumption of Escape Analgesic Medication.
Subjects recorded their use of escape medication each day on their diary card.
The primary population for this analysis was the intention-to-treat (ITT) population, which included all randomised subjects who received at least 1 dose of study medication and had on-treatment efficacy data. The primary analysis escape medication usage i.e. the number of days escape medication was used did not include any covariates.
The on-treatment data was calculated from all available data during the last three days. The number of days the escape medication was used out of the last three days taken in the study was compared between treatments using logistic regression with a cumulative logit model. From this analysis the frequency distribution (%) of number days escape medication was used was presented together with the odds ratio, p-value and 95% CI for the treatment contrasts.
All subjects who were randomised, received at least one actuation of study medication and had on-treatment efficacy data were included in the ITT population, used for this analysis.
Each secondary variable was tested using a two-sided significance level of α=0.05, unless otherwise specified. P-values of < 0.05 were considered statistically significant. If the overall treatment effect for the secondary variables was statistically significant then treatment comparisons was made between active treatments and placebo.
The nausea NRS 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 sick you felt throughout the day?" where 0 = not sick at all and 10 = very sick. A negative value indicates an improvement in nausea score from baseline.
The memory NRS 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 well you are able to remember what you have done in the past 24 hours?" where 0 = very well and 10 = not at all. A negative value indicates an improvement in memory score from baseline.
The appetite NRS 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 appetite has been throughout the day?" where 0 = very good and 10 = very poor. A negative value indicates an improvement in appetite score from baseline.
The concentration NRS 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 well have you been able to concentrate throughout the day e.g. when reading a newspaper?" where 0 = very well and 10 = not at all. A negative value indicates an improvement in concentration score from baseline.
Analysis of the change from baseline was assessed using ANCOVA, adjusting for the effects of the baseline value. The significance of the treatment effect, after adjusting for the baseline value, was assessed using the F-test from the ANCOVA. If found significant at the 5% level, then the mean difference between treatments together with 95% CI were presented.
The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). The minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Change in pain scores on-treatment were be compared between groups using analysis of covariance (ANCOVA). The baseline pain score was fitted as a covariate in the model. The significance of the treatment effect after adjusting for baseline pain score was assessed using the F-test from the ANCOVA. If this was significant at the 5% level, then the mean difference between treatments together with the 95% confidence interval was presented for Sativex versus placebo and THC versus placebo.
Time Frame All adverse events (AEs) occurring from the time of consent to post study follow up (14 - 20 days) were collected. All deaths and serious adverse events (SAEs) occurring within 28 days of the final dose of study medication were also collected.
Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010 Feb;39(2):167-79. doi: 10.1016/j.jpainsymman.2009.06.008. Epub 2009 Nov 5.
Responsible Party: Mr Richard Potts/ Clinical Operations Director, GW Pharmaceuticals Ltd.