Efficacy and safety study of arbaclofen placarbil in patients with spasticity due to spinal cord injury
Study design:Randomized, double-blind, placebo-controlled, two-period crossover.Objectives:To evaluate the efficacy and safety of arbaclofen placarbil (AP) in patients with spasticity secondary to spinal cord injury (SCI).Setting:United States and Canada.Methods:Patients received extended-release AP tablets 10, 20 or 30 mg every 12 h in one of two AP/placebo sequences, with 26 days of each treatment. The primary analysis compared Ashworth scale assessments of muscle tone between AP and placebo for the muscle group with maximum baseline Ashworth score. Secondary endpoints included a patient-rated Severity of Spasticity Scale.Results:In the primary analysis, AP significantly improved Ashworth scores compared with placebo over the dosing interval: least-squares mean reduction versus placebo was 0.60 for AP 20 mg (P=0.0059) and 0.88 for AP 30 mg (P=0.0007). The difference was significant for the pre-morning dose time point, 12 h after the prior evening dose, indicating that efficacy was maintained throughout the dosing interval. Treatment differences for AP 10 mg versus placebo were not significant. Severity of Spasticity ratings were significantly reduced for the combined 20/30-mg group versus placebo (P=0.018). No statistically significant differences between AP and placebo were observed for muscle strength. AP-related AEs were generally mild to moderate in intensity, and none led to early withdrawal or were serious.Conclusion:AP was well tolerated at all investigated dosages and, when administered at doses of 20 or 30 mg twice daily, was efficacious in reducing spasticity due to SCI.