Efficacy and safety of Ranquilon® in the therapy of patients with anxiety associated with neurasthenia and adjustment disorder: results of the double-blind, randomized, placebo-controlled, multicenter phase 3 clinical trial

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Objective: to evaluate the efficacy and safety of Ranquilon® (INN amide N-(6-phenylhexanoyl) glycyl-L-tryptophan)) tablets 1 mg2 at a dose of 6 mg per day (JSC “Valenta Pharm”, Russia) compared with placebo in the treatment of patients with anxiety in neurasthenia and adjustment disorder. Materialand methods. The clinical trial (CT) included a total of 220 patients with anxiety due to neurasthenia or adjustment disorder (adaptive reaction disorder) and a score on the Hamilton Anxiety Rating Scale (HARS) from 18 to 24 inclusive, the severity of asthenia on the self-assessment scale of asthenia (Multidimensional Fatigue Inventory, MFI-20) is more than 50 points, as well as at least 4 points on the severity subscale of the clinical global impression scale (Clinical Global Impression—Severity, CGI-S), who were randomly assigned to two groups and received double-blind treatment. Patients of group 1 (n=110) received Ranquilon® , 1 mg tablets, at a dose of 6 mg/day (2 tablets 3 times) for 28 days. Patients of group 2 (n=110) received PL in the same dosage regimen. The primary outcome measure for the clinical trial was the assessment of patient response rate (proportion of responders) as a ≥50% reduction in the mean total Hamilton Anxiety Rating Scale (HARS) score at Visit 3 (Day 29±1) compared to baseline at Visit 0 (days from -7 to -1). Secondary efficacy criteria included assessment of various parameters over time at visits 2 and 3 compared to the baseline (visit 0), in particular: on the HARS scale—the proportion of patients with a decrease in anxiety level (in the mean total score) by ≥50% and the proportion with ≤17 points, average anxiety score; for the CGI-I subscale—the proportion of patients with significant and pronounced improvement, on the CGI-S subscale—the proportion of patients with a score of 1 or 2 points, the mean total score of the change in the severity of the condition; on the MFI-20 scale—change in mean total score, the proportion of patients with a decrease in mean total score by 25%, by 50% and to ≤30 points, the mean total score for all subscale items; on the Spielberger-Hanin scale—change in the mean total score of personal anxiety and situational anxiety. To assess safety monitoring of adverse events (AEs), serious adverse events (SAEs), clinically significant deviations in vital signs, laboratory parameters, ECG parameters, etc. was analyzed. Results. The proportion of responders with a ≥50% reduction in HARS mean total score at Visit 3 (Day 29±1) compared to baseline (Visit 0) was statistically significantly higher (p<0.0001) in in group 1 (Ranquilon® ) compared with group 2 (PL), respectively, was 70.0% (n=77) and 24.5% (n=27) (difference—45.5% (n =50)). Evaluation of all secondary efficacy criteria also showed a statistically significant benefit of therapy in Group 1 compared to Group 2 (p><0.05). A total of 64 AEs were recorded in 44 (20.0%) patients: 43 AEs in 28 patients (25.5%) in Group 1 and 21 AEs in 16 (14.6%) patients in Group 2. There was no significant difference between treatment groups in the number of patients with AEs (p=0.063). In both groups, mild AEs were recorded; there were no patients with serious AEs (SAEs), SAEs with fatal outcome, or AEs that led to discontinuation of study therapy. No clinically significant abnormalities observed in vital signs, laboratory parameters, or ECG parameters. Conclusion. The superiority of Ranquilon® tablets 1 mg at a dose of 6 mg per day therapy over placebo in reducing anxiety in patients with conditions due to neurasthenia and adaptation disorder was confirmed. The drug demonstrated a favorable safety profile similar to that established for PL.><0.0001) in in group 1 (Ranquilon® ) compared with group 2 (PL), respectively, was 70.0% (n=77) and 24.5% (n=27) (difference—45.5% (n =50)). Evaluation of all secondary efficacy criteria also showed a statistically significant benefit of therapy in Group 1 compared to Group 2 (p<0.05).A total of 64 AEs were recorded in 44 (20.0%) patients: 43 AEs in 28 patients (25.5%) in Group 1 and 21 AEs in 16 (14.6%) patients in Group 2. There was no significant difference between treatment groups in the number of patients with AEs (p=0.063). In both groups, mild AEs were recorded; there were no patients with serious AEs (SAEs), SAEs with fatal outcome, or AEs that led to discontinuation of study therapy. No clinically significant abnormalities observed in vital signs, laboratory parameters, or ECG parameters. Conclusion. The superiority of Ranquilon® tablets 1 mg at a dose of 6 mg per day therapy over placebo in reducing anxiety in patients with conditions due to neurasthenia and adaptation disorder was confirmed. The drug demonstrated a favorable safety profile similar to that established for PL.