Tolperisone for the Treatment of Acute Muscle Spasm of the Back: Results from the Dose-Ranging Phase 2 STAR Study (NCT03802565)

OBJECTIVE: Use of skeletal muscle relaxants (SMRs) for acute muscle spasm is confounded by central nervous system adverse events (AEs), including somnolence. Tolperisone is an SMR that does not appear to be associated with somnolence. The aim of this study was to assess the safety and efficacy of tolperisone versus placebo in subjects with acute muscle spasm of the back. METHODS: STAR (NCT03802565) was a double-blind, randomized, placebo-controlled phase 2 study in subjects with back pain due to acute muscle spasm. Subjects were randomized 1:1:1:1:1 to tolperisone 50, 100, 150, or 200 mg three times daily (TID) or placebo for 14 days. The primary efficacy endpoint was subject-rated pain “right now” using a numeric rating scale on day 14. RESULTS: Subjects (tolperisone, n=337; placebo, n=78) were enrolled at 38 US clinical sites. Tolperisone was well tolerated, with AEs in 18.1% of subjects receiving tolperisone versus 14.1% of subjects receiving placebo. Headache (7.1%) and diarrhea (2.4%) were the most frequent AEs in tolperisone-treated subjects versus 3.8% and 0%, respectively, in placebo-treated subjects. Somnolence was reported in 1.2% and 2.6% of subjects treated with tolperisone and placebo, respectively. Mean change from baseline in numeric rating scale score of pain “right now” on day 14 was –3.5 for placebo versus –4.2, –4.0, –3.7, and –4.4 for tolperisone 50, 100, 150, and 200 mg TID, respectively (linear test of trend on the least-squares mean difference [treatment-placebo]; p=0.0539). In an analysis of pairwise estimates (treatment-placebo), the greatest numerical difference and significance were observed for tolperisone 200 mg TID (p=0.0040). Several secondary endpoints trended toward significance for tolperisone 200 mg TID versus placebo. CONCLUSION: Tolperisone 200 mg TID may be a promising treatment for acute muscle spasm, without the somnolence associated with SMRs. The safety and efficacy of tolperisone should be evaluated in a phase 3 trial.