Efficacy and Safety of a 2 mL Dilution of AbobotulinumtoxinA Compared with Placebo in Adult Patients with Cervical Dystonia (P1.029)

OBJECTIVE: To determine efficacy and safety of a 500 unit, 2 mL dilution of abobotulinumtoxinA (Dysport®) vs placebo in cervical dystonia (CD) patients. BACKGROUND: CD is characterized by involuntary cervical muscle contractions leading to sustained and painful head and neck postures. Botulinum toxin is FDA approved for the treatment of CD, and abobotulinumtoxinA is effectively administered in solutions up to 1 mL to affected muscles. Off-label 2 mL dilutions have been reported in the US and trials supporting this dilution would support dosing flexibility. METHODS: In this 12-week, phase 3b, double-blind study, CD patients were randomized (2:1) to abobotulinumtoxinA or placebo. Toxin-naive abobotulinumtoxinA patients received 500 units/2 mL in ≥2 affected neck muscles. AbobotulinumtoxinA CD subjects who had previously received botulinum treatment (non-naive) received 250-500 units/2 mL (2.5:1 abobotulinumtoxinA: previous onabotulinumtoxinA [Botox®] dose) into muscles injected during prior treatments. The primary endpoint was change from baseline to Week 4 (W4) in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. Safety was assessed over the 12-week study period. RESULTS: A total of 134 patients (abobotulinumtoxinA, n=89; placebo, n=45) were randomized and 129 (abobotulinumtoxinA, n=84; placebo, n=45) completed the W4 primary endpoint evaluation. Versus placebo, abobotulinumtoxinA patients experienced significantly greater changes from baseline in TWSTRS score at W4 (-2.5 versus -10.8, P <0.001; based upon the modified intent-to-treat population). Adverse events (AEs) occurred in 41[percnt] and 22[percnt] of abobotulinumtoxinA and placebo patients, respectively. Dysphagia was reported in 9[percnt] of treated patients. Other AEs in treated patients were muscle weakness, neck pain, and headache, none of which were reported with placebo. CONCLUSIONS: Data from this study indicate a 2 mL dilution of abobotulinumtoxinA was significantly more effective than placebo in CD patients. No unexpected AEs were observed relative to previous studies that used the 1 mL dilution volume in this patient population. Disclosure: Dr. Lew has received personal compensation for activities with Teva Pharmaceuticals, Solstice Neurosciences/USWM, Ipsen, Schering-Plough, Merz Pharmaceuticals, Abbott Laboratories, and Impax Laboratories. Dr. Snyder has received personal compensation for activities with Ipsen Biopharmaceuticals as an employee.