A Randomized, Double-Blind, Parallel Group Study to Compare the Safety and Efficacy of Arbaclofen Extended Release Tablets to Placebo and Baclofen for the Treatment of Spasticity in Patients with Multiple Sclerosis (P3.034)

OBJECTIVE: To compare the efficacy and safety of Arbaclofen Extended Release Tablets (AERT) to placebo and baclofen over 12 weeks of treatment in patients with spasticity due to multiple sclerosis (MS). BACKGROUND Spasticity is common in MS and is associated with significant morbidity. The standard treatment is oral administration of baclofen, a γ-aminobutyric acid-b (GABA-b) receptor agonist. Baclofen is a racemic mixture and its efficacy is thought to be due to the R-enantiomer (arbaclofen). Therapeutic doses of baclofen can cause CNS side effects and decreased adherence and tolerability. AERT can reduce dosing frequency and adverse events. DESIGN/METHODS This was a multicenter, randomized, double blind, active and placebo controlled parallel group study in adults with spasticity due to MS. The study compared AERT 20 mg BID with baclofen tablets 20 mg QID and matching placebo. The dose was titrated over 4 weeks followed by a 12-week maintenance period. The co-primary endpoints were the mean changes in Total Numeric-transformed Modified Ashworth Scale (TNmAS) and Clinician Global Impression of Change (CGIC) at the end of the maintenance period. RESULTS Of 354 randomized subjects, 59.0[percnt] had relapsing remitting and 36.7[percnt] had secondary progressive MS. The average baseline TNmAS score was 7.78. TNmAS and CGIC were statistically significant in favor of AERT group compared with placebo, while differences between AERT and baclofen were not statistically significant. MS Spasticity Scale (MSSS-88) showed a statistically significant improvement in AERT group compared with placebo. Epworth Sleepiness Scale (ESS) showed a statistically significant increase in sleepiness in the baclofen group, but not in the AERT group compared to placebo. Drowsiness and dizziness were less frequent in AERT group compared with baclofen. CONCLUSIONS This study demonstrated that AERT administered twice a day was efficacious, safe, and better tolerated than baclofen in MS patients with spasticity. Study Supported by Osmotica Pharmaceutical Disclosure: Dr. Kantor has received personal compensation for activities with Avanir, Genzyme, Biogen Idec, Novartis, Questcor, Teva, Depomed, Osmotica, and Allergan. Dr. Wynn has received research support from Acorda, Avanir, EMD Serono, Genzyme, GlaxoSmithKline, Hoffman-LaRoche, Novartis, Ono Pharmaceutical Co, Opexa Therapeutics, Osmotica, Pfizer, and Questcor. Dr. Dentiste has received personal compensation for activities with Osmotica as an employee. Dr. Aikman has received personal compensation for activities with Osmotica as an employee. Dr. Kaba has received personal compensation for activities with Osmotica Pharmaceutical as an employee.