Multicenter, open, randomized study with active control (isoniazid) to evaluate the early antibacterial activity, safety and pharmacokinetics of the drug PBTZ169 (capsules 80 mg) when used in patients with first-diagnosed tuberculosis of the respiratory system with bacterial excretion and saved bacterial susceptibility to isoniazid and rifampicin
This phase 2a study is aimed to evaluate the early bactericidal activity of a new anti-tuberculosis drug PBTZ169 (capsules 80 mg), and its results will allow preliminary evaluate antimycobacterial properties of PBTZ169 and confirm a potentially more effective dose for subsequent studies. This study is an open, randomized comparative efficacy (on the parameter of early bactericidal activity), safety and pharmacokinetics study of PBTZ169 in patients with first-diagnosed lung tuberculosis and preserved sensitivity to base antimycobacterial drugs: rifampicin and isoniazid. Within the framework of the study, it is planned to use the studied drugs (PBTZ169 and isoniazid) as monotherapy within 14 days. Isoniazid is used as a "positive control", that is, in order to determine whether the method of assessing efficacy on the parameter of early bactericidal activity is working.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Early Bactericidal Activity (0-14)
Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): agar inoculation, the mean of two measurements at the Visit
Time frame: 14 days after the onset of monotherapy
Early Bactericidal Activity (0-14)
Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): PCR, the mean of two measurements at the Visit
Time frame: 14 days after the onset of monotherapy
Early Bactericidal Activity (0-2)
EBA (0-2): agar inoculation, the mean of two measurements at the Visit
Time frame: 2 days after the onset of monotherapy
Early Bactericidal Activity (0-7)
EBA (0-7): agar inoculation, the mean of two measurements at the Visit
Time frame: 7 days after the onset of monotherapy
Early Bactericidal Activity (0-2)
EBA (0-2): PCR, the mean of two measurements at the Visit
Time frame: 2 days after the onset of monotherapy
Early Bactericidal Activity (0-7)
EBA (0-7): PCR, the mean of two measurements at the Visit
Time frame: 7 days after the onset of monotherapy
Peak Plasma Concentration (Сmax) of PBTZ169
Peak plasma concentration (Сmax) of PBTZ169 for multiple dosing
Time frame: Up to 72 hours after the last drug administration
Minimal Plasma Concentration (Сmin) of PBTZ169
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Minimal plasma concentration (Сmin) of PBTZ169: concentration measurement following single dosing
Time frame: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)
Residual Concentration (Ctrough) of PBTZ169
Residual concentration (Ctrough) of PBTZ169, measured 24 hours after the first dose administration, prior to the last dose, and 24 hours after the last dose
Time frame: Up to 72 hours after the last drug administration
Minimal Plasma Concentration (Сmin) of PBTZ169
Minimal plasma concentration (Сmin) of PBTZ169: multiple dosing
Time frame: Up to 72 hours after the last drug administration
Time to Reach Maximum Concentration (Tmax) of PBTZ169
Time to reach maximum concentration (Tmax) of PBTZ169 after single oral administration in different doses
Time frame: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)
Time to Reach Maximum Concentration (Tmax) of PBTZ169
Time to reach maximum concentration (Tmax) of PBTZ169 after multiple oral administration in different doses
Time frame: Up to 72 hours after the last drug administration
AUC(0-24)
Area under the plasma concentration of PBTZ169 versus time curve in frames \[0-24 hours\]
Time frame: Up to 24 hours after the first drug administration
Peak Plasma Concentration (Сmax) of PBTZ169
Peak plasma concentration (Сmax) of PBTZ169: concentration measurement following single dosing
Time frame: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)
AUC(0-24)
Area under the plasma concentration of PBTZ169 versus time curve in frames \[0-24 hours\] for the last dosing (Day 14)
Time frame: Up to 24 hours after the last drug administration
AUC (0-t)
Area under the plasma concentration of PBTZ169 versus time curve in frames \[0-last concentration above lower limit of quantification (LLoQ)\]
Time frame: Up to 72 hours after the last drug administration
AUC(0-∞) of PBTZ169
Area under the plasma concentration versus time curve in frames \[0-∞\]
Time frame: Up to 72 hours after the last drug administration
Accumulation Ratios for the PK Parameters AUC(0 -24)
Accumulation ratios for the PK parameter AUC(0 -24): AUC(0- 24,ss)/AUC(0 -24), Day 1, on the original scale
Time frame: 24 hours after the first and the last drug administration
Average Concentration (Css,av) of PBTZ169
Average steady-state concentration in the dosing interval following multiple dosing was evaluated as the ratio AUC0 24/τ (τ = the dosing interval)
Time frame: Up to 72 hours after the last drug administration
Fluctuations (%) in the Dosing Interval
Fluctuations (%) in the dosing interval after multiple dosing ((Cmax - Cmin) × 100%/Css,av)
Time frame: Up to 72 hours after the last drug administration
Total (Plasma) Clearance (Clt) of PBTZ169
Clt/F (apparent total clearance following single and multiple oral administration) was calculated using the following formula: Cl\_t/F=D/AUC where D is the daily dose of the drug.
Time frame: 24 hours after the first drug administration
Total (Plasma) Clearance (Clt) of PBTZ169
Clt/F (apparent total clearance following single and multiple oral administration) was calculated using the following formula: Cl\_t/F=D/AUC where D is the daily dose of the drug.
Time frame: 24 hours after the last drug administration
Volume of Distribution (Vd) of PBTZ169
Distribution volume Vd for a dosing interval of 72 hours after the last dose
Time frame: Up to 72 hours after the last drug administration
Plasma Half-life Time (T1/2) of PBTZ169
Time frame: 24 hours after the fist drug administration
Plasma Half-life Time (T1/2) of PBTZ169
Time frame: 24 hours after the last drug administration
Elimination Constant (Kel) of PBTZ169
Apparent terminal elimination rate constant was evaluated based on the regressional dependence of log-transformed concentrations ln(C) on time for the terminal log- linear part of the concentration-time curve.
Time frame: 24 hours after the first drug administration
Elimination Constant (Kel) of PBTZ169
Apparent terminal elimination rate constant was evaluated based on the regressional dependence of log-transformed concentrations ln(C) on time for the terminal log- linear part of the concentration-time curve.
Time frame: 72 hours after the last drug administration