Efficacy and safety of Vespireit® (buspirone) prolonged-release tablets (PR) 15 mg in the therapy of patients with functional dizziness: results of the double-blind, placebo-controlled, multicenter, randomized, phase 3 clinical trial

Abstract

Functional dizziness (FD) is one of the most common causes of chronic dizziness for which there is no effective drug therapy, highlighting the importance of searching for new treatment technologies. Objective: to evaluate the efficacy and safety of Vespireit® (INN buspirone) prolonged-release tablets 15 mg2 (JSC “Valenta Pharm”, Russia) compared with placebo in the treatment of patients with autonomic dysfunction syndrome accompanied by FD. Material and methods . The clinical trial (CT) included a total of 268 patients with autonomic dysfunction syndrome accompanied by FD and a DHI (The Dizziness Handicap Inventory) dizziness scale score of 36 to 52 inclusive, who were randomly divided into 2 groups and treated in a double-blind fashion. 135 patients (Group 1) received Vespireit® prolonged-release tablets 15 mg at a dose of 15 mg (1 tablet) once daily for 28 days. 133 patients (Group 2) received placebo at the same dosage regimen. Treatment was given against a background of vestibular gymnastic exercises. The primary outcome of the clinical trial was assessment of patient response rate (proportion of responders), i.e., a ≥50% reduction in total DHI for dizziness score at Visit 5 (day 28±1) compared with baseline (Visit 1, day 1). Secondary efficacy measures included assessment of: 1) treatment response rates (≥50% reduction in DHI total score compared to Visit 1) at Visits 2, 3, and 4; 2) DHI total score at Visits 2, 3, 4, and 5; 3) changes in DHI total score at Visits 2, 3, 4, and 5 compared to Visit 1; 4) proportion of patients with a 30% or greater reduction in DHI scale dizziness compared with baseline at Visit 2, 3, 4, and 5; 5) time elapsed until total DHI score decreased by ≥50% compared to baseline; 6) time elapsed until total DHI score decreased by ≥30% compared to baseline; 7) changes in Digital Rating Scale (DRS) score from Visit 1 to Visit 2, 3, 4, 5; 8) scores on the DRS at Visits 2, 3, 4, 5; 9) proportion of patients with different response to treatment on the Likert scale at Visits 2, 3, 4, and 5. Additional secondary criteria of efficacy were also assessed: total Hamilton Depression Rating Scale (HDRS) score at Visits 4 and 5; change in total Hamilton scale score at Visits 4 and 5 compared to Visit 1. The safety criterion assessed in the clinical trial was monitoring of adverse events (AEs), clinically significant deviations in vital signs, laboratory parameters, and ECG parameters. Results. The proportion of responders with a ≥50% reduction in DHI total score at Visit 5 (Day 28±1) compared to baseline (Visit 1, Day 1) was 68.7% (n=92) in Group 1, which was 52.9% more than in Group 2 – 15.8% (n=21) (p<0.0001). Evaluation of all secondary (including additional) efficacy criteria also showed a statistically significant benefit of therapy in Group 1 compared to Group 2 (p<0.0001). A total of 61 AEs were recorded in 46 (17.2%) patients: 30 AEs in 21 (15.6%) patients in Group 1 and 31 AEs in 25 (18.8%) patients in Group 2. There was no significant difference between treatment groups in the number of patients with AEs (p=0.5196). In both groups, there were no patients with AEs with severity ≥3, serious AEs (SAEs), SAEs with fatal outcome, or SAEs that led to discontinuation of study therapy. No clinically significant abnormalities were noted during assessment of vital signs, laboratory parameters, or ECG parameters Conclusion. The superiority of Vespireit® prolonged-release tablets (PR) 15 mg therapy over placebo in reducing FD in patients with autonomic dysfunction syndrome was confirmed. The drug demonstrated a favorable safety profile comparable to placebo.