Tolerability of Once-Daily Cyclobenzaprine Hydrochloride Modified-Release 15 mg and 30 mg for Low Back and Neck Pain Associated with Muscle Spasm

Data were pooled from two identical-design, double-blind, placebo-controlled studies in patients with acute muscle spasm pain (n=504). Patients were randomized to: cyclobenzaprine hydrochloride modified-release (CMR) 15mg (n=127) or 30mg (n=126) once-daily in the evening, cyclobenzaprine immediate-release (CIR) 10mg 3x daily (n=123), or placebo (n=128) for 14 days. Primary efficacy assessments (patient rating of medication helpfulness and physician clinical global assessment) were evaluated on day 4 (after 3 consecutive days of treatment). Adverse events (AEs) and daytime drowsiness were among the secondary outcome measures. Overall, 330 (65.5%) patients completed 14 days of treatment. Patients reported relief of acute muscle spasm pain following CMR 15mg and 30mg. No appreciable differences in clinical efficacy were noted between CMR and CIR in this respect. The majority of AEs were mild (range 53.3-67.4%) across all groups, and the most common AEs (³5% of patients) were similar and consisted of dry mouth, constipation, dizziness, headache, and somnolence. Incidence of somnolence was higher for CIR (7.3%) compared with CMR 15mg (0.8%) and 30mg (1.6%). At day 4, rates of ²a lot of drowsiness² or ²extreme drowsiness² were 25.4% for CIR, 18.8% for CMR 15mg, and 19.8% for CMR 30mg groups. Two serious AEs were reported during the post-treatment period (unrelated to CMR or CIR). 174/504 patients discontinued from the studies, for reasons including insufficient response (n=16) and AEs (n=25). Discontinuations due to AEs were greater for CIR (11.4%) than CMR 15mg (1.6%) and 30mg (4.8%), or placebo (2.3%). The most common AE leading to withdrawal was somnolence (6.5%, CIR; 0%, CMR 15mg; 1.6%, CMR 30mg). In conclusion, once-daily CMR was generally well-tolerated with less daytime drowsiness relative to CIR in the treatment of acute muscle spasm pain.

ECR Pharmaceuticals sponsored this study. Cephalon, Inc. acquired the North American rights to Cyclobenzaprine Hydrochloride Modified-Release (AMRIX™) in August, 2007.