Author Of 1 Presentation
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.