Comparative efficacy and safety of Vespireit® and Arlevert® in the treatment of patients with functional dizziness: results of an open-label multicenter randomized phase IV clinical trial

Functional dizziness (FD) is one of the most common causes of chronic dizziness. Objective: a comparative assessment of the efficacy and safety of Vespireit® (buspirone), 15 mg prolonged-release tablets, versus Arlevert® tablets (cinnarizine 20 mg + dimenhydrinate 40 mg) in the treatment of patients with FD. Material and methods. The clinical trial (CT) included 160 patients with FD and scores on the Dizziness Handicap Inventory (DHI) ≥31 points and the Mean Vertigo Score (MVS) ≥1.5 points, who were randomized into two groups. Patients in group 1 (n=80) received Vespireit at a dose of 15 mg (1 tablet) once daily for 28 days. Patients in group 2 (n=80) received Arlevert 1 tablet 3 times daily for 28 days. Treatment was administered against a background of vestibular gymnastics exercises. The primary efficacy endpoint (PEE) was the change in mean MVS score at visit 1-3 (day 28±1) compared with baseline (visit 1-1, day 1). Secondary efficacy endpoints (SEEs) included assessment compared with baseline (visit 1-1, day 1): 1) change in mean MVS score by visit 1-2 (day 7±1); 2) change in the proportion of patients with a ≥50% reduction in mean DHI score by visit 1-3; 3) change in mean score on the numerical rating scale (NRS) by visits 1-2 (day 7±1) and 1–3 (day 28±1); 4) assessment by patient and physician of clinical improvement in proportions of patients and mean scores on the Clinical Global Impression Scale-Improvement Scale (CGI-I) by visits 1-2 (day 7±1) and 1-3 (day 28±1). In case of recurrence (exacerbation of dizziness symptoms), a second course of treatment with the study drugs and a similar assessment using the scales were performed. At the end-of-study visit (day 365±7 from visit 1-1), the proportion of patients with recurrence and the duration of the remission period were assessed. Safety criteria included assessment of adverse events (AEs), clinically significant deviations in vital signs, laboratory parameters, and electrocardiography (ECG) parameters. Results. Assessment of the PEE revealed no significant differences between the groups (p=0.0814); the lower limit of the 95% confidence interval (-0.07 points) did not exceed the non-inferiority margin (-0.3), thus demonstrating non-inferior efficacy of Vespireit compared with Arlevert. Assessment of most SEEs showed a statistically significant advantage of therapy in group 1 compared with group 2: reduction in mean MVS score by visit 1-2 (p=0.0427); proportion of responders with ≥50% reduction in mean DHI score by visit 1-3 (p=0.0433); reduction in mean NRS score by visits 1-2 (p=0.0230) and 1-3 (p=0.12244); proportion of responders with marked improvement (1 point) and considerable improvement (2 points) on CGI-I by visits 1-2 and 1-3 (patient assessment p=0.0453 and p=0.0481, p=0.0101 and p=0.8584; physician assessment p=0.0725 and p=0.0321, p=0.0169 and p=0.8622). A similar anti-relapse effect was established in groups 1 and 2 [proportion of patients without recurrence in group 1 – 94.87% (n=74), in group 2 – 93.67% (n=74; p=1.0000); duration of remission in group 1 – 359.14±38.08 days, in group 2 – 361.33±15.77 days (p=0.1798)]. A total of 84 AEs were recorded in 35 (21.88%) patients: 52 AEs in 18 (22.5%) patients in group 1 and 32 AEs in 17 (21.25%) in group 2. No significant difference was found between the groups in the number of patients with AEs (p=0.8483). During the CT, no serious adverse events (SAEs), fatal SAEs, or AEs leading to discontinuation of therapy were recorded. No clinically significant deviations from normal were observed in the assessment of vital and laboratory parameters or ECG parameters. Conclusion. Assessment of the PEE demonstrated non-inferior efficacy, and for a number of SEEs, superiority of therapy with Vespireit over therapy with Arlevert was established in reducing manifestations of FD. The drugs demonstrated a comparably high level of anti-relapse effect and a favorable safety profile.