Multicenter, randomized, double-blind study of the efficacy and safety of prolonged release tolperisone hydrochloride 450 mg (Mydocalm® Long, once daily) and tolperisone hydrochloride 150 mg (three times daily) for acute non-specific lower back pain

Prolonged release tolperisone hydrochloride 450 mg (PRTH 450) is a dosage form that is convenient for patients, since it reduces the frequency of drug administration per day: from three immediate release tablets of 150 mg (TH 150) to one tablet of PRTH 450.
Objective: to evaluate the therapeutic efficacy and safety of the new dosage form of PRTH 450 (Mydocalm® Long, once a day) in comparison with TH 150 (Mydocalm^® administered three times per day) in acute non-specific lower back pain (LBP).
Patients and methods. Study No. 84158 – a multicenter, randomized, double-blind, phase III, active control study of no less efficiency in two parallel groups of adult patients (mean age: 41.3 and 41.88 years) with acute non-specific LBP. From 05.09.2017 to 07.05.2018, 239 patients with acute non-specific LBP were included in the study. The two placebo method was used to mask the prescribed treatment. Inpatients or outpatients were randomly assigned to therapy with PRTH 450 once a day in combination with placebo three times a day or TH 150 three times a day in combination with placebo once a day.
For 14 days, after a meal, patients received oral PRTH 450 once a day as an active drug and placebo three times per day or oral TH 150 three times per day and placebo once a day. Follow-up visits were carried out after 3.7±1 and 14±2 days. Patients in whom the study drugs did not significantly reduce pain were allowed to additionally use diclofenac tablets up to 50 mg three times a day. The primary efficacy endpoint was the percentage change in baseline disability assessed by the Roland-Morris Disability Questionnaire (RMQ) at 14 days (treatment completion). Secondary efficacy endpoints were the percentage change in baseline disability after 3 and 7 days, the difference in pain intensity on the visual analogue scale (VAS) after 3, 7, and 14 days, the patient's overall impression of the daily change in his condition, the time before symptoms began to decrease, change in range of motion, measured by the fingertips to floor distance during an attempt to reach for the floor with the fingertips after 3, 7 and 14 days, as well as the total dose of diclofenac for additional pain relief. Safety indicators and their changes were assessed at each visit and in each treatment group. The presence of adverse events (AEs) was determined based on patient complaints and general examination results, measurements of vital signs (blood pressure, heart rate), 12-lead electrocardiography results, and blood and urine tests throughout the study.
Results and discussion. In 14 days, the limitation of daily activity according to RMQ decreased by 80.5±18.19% in the PRTH 450 group and by 78.9±15.79% in the TH 150 group, after 3 days – by 21.9±17.07 and 19,9±15.72%, respectively. There was a significant decrease in pain at rest and during movement according to the VAS during treatment, as well as an increase in the range of motion in the lumbar spine in both groups. During the follow-up period, patients took an average of 15.1 tablets of diclofenac in the PRTH 450 group and 16.1 tablets in the TH 150 group. At the end of the study, 74.3% of patients in the PRTH 450 group and 70.9% of patients in the TH 150 group noted a «marked improvement» on the scale of the overall assessment of their condition. 21 AEs in 16 (13.4%) patients in the PRTH 450 group and 23 AEs in 21 (17.5%) patients in the TH 150 group were registered. No statistically significant differences were found between the two groups for the primary study endpoint (p=0.475, Fisher's exact test), AEs, and for all secondary study endpoints.
Conclusion. The results of the study showed that in acute nonspecific LBP, PRTH 450 (Mydocalm® Long) administered once daily has no less efficacy and safety than TH 150 (Mydocalm^®).

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