75 - Tolperisone for Acute Muscle Spasm: Dose-Ranging STAR Study
Srinivas Nalamachu1, Randall Kaye2, Joseph Pergolizzi3
1Mid America PolyClinic, Overland Park, KS, USA. 2Neurana Pharmaceuticals, Inc., San Diego, CA, USA. 3NEMA Research, Naples, FL, USA
Purpose Back pain is common and mostly attributed to acute musculoskeletal spasm with no apparent underlying cause. Skeletal muscle relaxants (SMRs) are effective for the treatment of back pain due to acute muscle spasm but are typically not preferred because of adverse central nervous system effects, such as somnolence. Tolperisone, a centrally acting, nonopioid SMR in clinical development in the United States, does not seem to exhibit the central nervous system effects seen with other available treatments. The objective of this study was to assess the safety and efficacy of tolperisone50, 100, 150, and 200mg three times daily (TID)compared with placebo in patients with acute muscle spasm of the back. Methods STAR (ClinicalTrials.gov, NCT03802565) was a double-blind, randomized, placebo-controlled, phase 2 study. Eligible patients were aged 18-65 years with current back pain or stiffness due to acute muscle spasm starting ≤7 days before study entry and lasting for >8 weeks after the last episode of back pain. Patients were randomly assigned 1:1:1:1:1 to receive tolperisone 50, 100, 150, or 200 mg TID or placebo for 14 days. Patients could receive acetaminophen 500 mg TID as rescue medication. The primary efficacy end point was subject-rated pain “right now” using a numeric rating scale (NRS; 0=no pain to 10=worst possible pain) on day 14. Secondary end points included onset of action, duration of relief, use of rescue medication, and safety. The study was approved by the institutional review board at each site. Results Patients (N=415) were enrolled at 38 US sites (tolperisone,n=337;placebo, n=78). Tolperisone was well tolerated, and most patients completed 14 days of treatment (92.6% tolperisone; 88.5% placebo). Adverse events (AEs) occurred in 18.1% vs 14.1% of patients receiving tolperisone or placebo, respectively; headache (7.1%) and diarrhea (2.4%) were the most frequent AEs in tolperisone-treated patients vs 3.8% and 0%, respectively, in placebo-treated patients. Somnolence was reported in 1.2% and 2.6% of patients treated with tolperisone or placebo, respectively. The visual analog scale for subject-reported sleepiness on day 4 was similar in all treatment groups, including placebo. No serious AEs or deaths occurred. Day 14 mean change from baseline in NRS rating of pain “right now” was −3.5 for placebo vs −4.2, −4.0, −3.7, and −4.4 for tolperisone 50, 100, 150, and 200 mg TID, respectively. The linear test of trend on the least squares mean differences (treatment-placebo) approached statistical significance (p=0.0539).In an analysis of pairwise estimates (treatment-placebo), the greatest numerical difference and significance was observed for tolperisone 200 mg TID (p=0.0040). Two key secondary end points—patient rating of medication helpfulness and patient’s global impression of change—trended toward significance for the tolperisone 200 mg TID group vs placebo (p=0.0656 and p=0.0526, respectively). Certain subcategories of the Oswestry Pain and Disability Index (ie, personal care, walking, and social life) trended toward significance for comparison of tolperisone 200 mg TID vs placebo at day 14. Conclusions Tolperisone was well tolerated and effective in patients with acute muscle spasm of the back and was associated with low rates of somnolence. Tolperisone 200 mg TID may be a promising treatment for the management of acute muscle spasm, without the somnolence that typically occurs with SMRs.