Author Of 2 Presentations
P1094 - Effect of nabiximols cannabinoid oromucosal spray on depressive symptoms, suicidality, and cognition in patients with multiple sclerosis (MS) (ID 1463)
Abstract
Background
Substantial evidence has shown nabiximols, a complex botanical mixture containing delta-9-tetrahydrocannabinol and cannabidiol as the principal cannabinoids, can reduce spasticity associated with MS. This analysis assesses whether nabiximols affects other patient outcomes such as depressive symptoms, suicidality, and cognition.
Objectives
Report the effect of nabiximols on depression, suicidality, and cognition using data from 2 placebo-controlled randomized controlled trials, GWSP0604 (12 weeks) and GWMS1137 (48 weeks), in patients with spasticity due to MS.
Methods
Mood and suicidality were assessed using the Beck Depression Inventory-II (BDI-II) in both trials. In GWMS1137, suicidality was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) and working memory/processing speed using the Paced Auditory Serial Addition Test (PASAT). The combined PASAT total score was calculated combining both PASAT-3 and -2 tests scores (total of 120 points). Outcome differences between nabiximols and placebo are summarized.
Results
241 patients from GWSP0604 and 121 from GWMS1137 were included. The baseline and end-of-treatment mean BDI-II total scores were 8.7 vs 9.5 for nabiximols and 9.7 vs 10.4 for placebo in GWSP0604, and 15.7 vs 12.5 for nabiximols and 13.5 vs 11.1 for placebo in GWMS1137. Differences between nabiximols and placebo of the BDI-II change from baseline adjusted means were -0.06 (-1.62, 1.49) in GWSP0604 (no significant difference) and -0.29 (-2.91, 2.33) in GWMS1137 (statistically non-inferior). Question 9 of BDI-II (suicidal thoughts or wishes) showed no notable treatment differences in either trial, with only 1 patient treated with nabiximols reporting a score ≥2. On the Columbia-Suicide Severity Rating Scale, 3 (5.1%) patients randomized to placebo and 1 (1.6%) to nabiximols had a ‘flag’ (ie, ‘Yes’ as a response), but further questioning revealed no emergent suicidal ideations or behavior in any of these patients. For GWMS1137, the baseline and end-of-treatment PASAT total score means were 71.3 vs 78.6 for nabiximols and 74.5 vs 82.7 for placebo; increases may reflect practice effects. Treatment difference of the adjusted mean was -1.47 (-6.41, 3.48), indicating nabiximols does not adversely affect working memory/cognitive processing speed in MS patients over a 48-week period compared with placebo.
Conclusions
Nabiximols had no notable effects on depression, suicidality, or working memory/processing speed in patients with MS. Funding: Greenwich Biosciences, Inc.
P1109 - Safety and efficacy of nabiximols in patients with multiple sclerosis-associated spasticity: post hoc analyses of a controlled enrichment design study (ID 546)
Abstract
Background
Nabiximols, a cannabinoid oromucosal spray, improved spasticity vs placebo in multiple sclerosis patients in a phase 3 trial (NCT00681538). Initial responders with ≥20% decrease in average daily numeric rating scale [NRS] spasticity score in Phase A single-blind lead-in period with nabiximols were randomized to nabiximols or placebo in Phase B double-blind period. Efficacy was evaluated relative to Phase B randomization baseline and not Phase A screening baseline (Novotna et al. Eur J Neurol 2011;18:1122–31).
Objectives
This post hoc analysis assessed the safety profile of nabiximols in responders vs nonresponders during Phase A (4 weeks) and efficacy outcomes for nabiximols vs placebo during Phase B (12 weeks) relative to Phase A baseline.
Methods
Incidence of AEs was assessed during Phase A and B. Percent change in NRS spasticity score and daily spasm frequency and the proportion of caregivers reporting an improvement in patients’ functional abilities on a Caregiver Global Impression of Change (CGIC) scale were assessed at the end of Phase B relative to Phase A baseline.
Results
Of 572 patients enrolled, 266 were responders at the end of Phase A; 241 of these patients were then randomized to nabiximols (n=124) or placebo (n=117) in Phase B. During Phase A, 40% of responders and 53% of nonresponders had an AE. The AE profile was similar between the 2 groups, except dizziness, which occurred more frequently in nonresponders vs responders (18% vs 10%). During Phase B, 53% of patients on nabiximols reported ≥1 AE vs 49% on placebo; 9 patients on nabiximols discontinued due to an AE vs none on placebo. The subcohort of responder patients from Phase A randomized to continue nabiximols or switch to placebo in Phase B had similar mean percent reductions in NRS spasticity (44% for both) and spasm frequency (47% vs 45%) during Phase A. At the end of Phase B, mean percent decrease from Phase A baseline in spasticity NRS was 46% for nabiximols vs 34% for placebo (P=0.011); mean percent decrease in spasm frequency was 44% for nabiximols vs 24% for placebo (P=0.006). Change of ≥1 point from Phase A baseline on the CGIC scale was reported for 68% of patients on nabiximols vs 43% on placebo during Phase B.
Conclusions
Nabiximols was well tolerated and provided continued benefit to patients who remained on therapy in Phase B, with a variable loss of efficacy in patients who switched from nabiximols in Phase A to placebo in Phase B. Funding: Greenwich Biosciences, Inc.