Evaluation of Safety of Thiosonide in Multiple Doses in Patients with Multidrug, Pre-extensively or Extensively Drug-Resistant Pulmonary Tuberculosis: a Multicenter Randomized Controlled Study

The objective: to evaluate safety of Thiosonide in multiple doses, a new domestic anti-tuberculosis drug, in patients with multidrug, pre-extensively or extensively drug-resistant pulmonary tuberculosis. Subjects and Methods. The safety of Thiosonide was assessed from November 24, 2014 to May 17, 2019 within a multicenter, 12-week, double-blind, randomized, placebo-controlled clinical study (Protocol no. TIO22, Permit no. 661 dated November 24, 2014 by the Russian Ministry of Health). The study included 160 patients aged 18 to 60 years, who were undergoing inpatient or outpatient treatment in 13 clinical centers with the verified diagnosis of MDR TB, pre-XDR TB and XDR TB. Against the background of standard anti-tuberculosis therapy, patients received 200, 400 or 600 mg of Thiosonide or placebo once a day. Treatment duration made 84 days. The following parameters were used to assess safety of the drug: frequency and severity of adverse events (AEs) and serious adverse events (SAEs), number of cases of early discontinuation of the drug due AEs and SAEs, changes in vital signs during a physical examination, abnormal parameters of laboratory and instrumental tests and examinations. Results. It has been demonstrated that Thiosonide is well-tolerated and safe. During the study, 100 AEs were reported, but only one of them (1%), which was an elevated creatine phosphokinase level, was definitely related to the investigated drug. Statistical analysis reveal no significant relationship between the frequency of AEs and dosage of the drug. Conclusion. A safety study of Thiosonide, an original anti-tuberculosis drug, in patients with MDR, pre-XDR and XDR pulmonary TB with multiple administration in doses of 200 mg, 400 mg and 600 mg showed its good tolerability, accompanied by single AEs, of which no more than 1% were definitely related to the investigated drug. Due to the above, Thiosonide can be considered as a promising drug for the treatment of MDR/XDR TB patients.