Trial Outcomes & Findings for Phase 2a Study of PBTZ169 (NCT NCT03334734)

NCT ID: NCT03334734

Last Updated: 2020-03-09

Results Overview

Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): agar inoculation, the mean of two measurements at the Visit

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: 14 days after the onset of monotherapy
• Results posted on: 2020-03-09

Participant Flow

Participant milestones

Measure	PBTZ169, 160 mg 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Overall Study STARTED	4	4	7	1
Overall Study COMPLETED	4	4	5	1
Overall Study NOT COMPLETED	0	0	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 2a Study of PBTZ169

Baseline characteristics by cohort

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days	Total n=16 Participants Total of all reporting groups
Age, Continuous	49.0 years STANDARD_DEVIATION 13.0 • n=5 Participants	48.8 years STANDARD_DEVIATION 10.7 • n=7 Participants	43.7 years STANDARD_DEVIATION 14.8 • n=5 Participants	41.0 years STANDARD_DEVIATION 0 • n=4 Participants	46.1 years STANDARD_DEVIATION 12.3 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	14 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	1 Participants n=4 Participants	16 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Russia	4 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants	1 participants n=4 Participants	16 participants n=21 Participants

PRIMARY outcome

Timeframe: 14 days after the onset of monotherapy

Population: FAS

Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): agar inoculation, the mean of two measurements at the Visit

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Early Bactericidal Activity (0-14)	0.061 CFU per 1 mL of sputum Standard Deviation 0.085	0.015 CFU per 1 mL of sputum Standard Deviation 0.025	0.071 CFU per 1 mL of sputum Standard Deviation 0.126	0.237 CFU per 1 mL of sputum Standard Deviation 0

PRIMARY outcome

Timeframe: 14 days after the onset of monotherapy

Population: FAS

Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): PCR, the mean of two measurements at the Visit

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Early Bactericidal Activity (0-14)	0.038 cell count per 1 mL of sputum Standard Deviation 0.081	-0.014 cell count per 1 mL of sputum Standard Deviation 0.048	0.097 cell count per 1 mL of sputum Standard Deviation 0.136	-0.099 cell count per 1 mL of sputum Standard Deviation 0

SECONDARY outcome

Timeframe: 2 days after the onset of monotherapy

Population: FAS

EBA (0-2): agar inoculation, the mean of two measurements at the Visit

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Early Bactericidal Activity (0-2)	0.496 CFU per 1 mL of sputum Standard Deviation 0.615	0.124 CFU per 1 mL of sputum Standard Deviation 0.095	-0.003 CFU per 1 mL of sputum Standard Deviation 0.452	-0.243 CFU per 1 mL of sputum Standard Deviation 0

SECONDARY outcome

Timeframe: 7 days after the onset of monotherapy

Population: FAS

EBA (0-7): agar inoculation, the mean of two measurements at the Visit

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Early Bactericidal Activity (0-7)	0.078 CFU per 1 mL of sputum Standard Deviation 0.136	0.026 CFU per 1 mL of sputum Standard Deviation 0.069	0.064 CFU per 1 mL of sputum Standard Deviation 0.102	0.090 CFU per 1 mL of sputum Standard Deviation 0

SECONDARY outcome

Timeframe: 2 days after the onset of monotherapy

Population: FAS

EBA (0-2): PCR, the mean of two measurements at the Visit

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Early Bactericidal Activity (0-2)	-0.110 cell count per 1 mL of sputum Standard Deviation 0.872	0.007 cell count per 1 mL of sputum Standard Deviation 0.084	0.085 cell count per 1 mL of sputum Standard Deviation 0.397	0.627 cell count per 1 mL of sputum Standard Deviation 0

SECONDARY outcome

Timeframe: 7 days after the onset of monotherapy

Population: FAS

EBA (0-7): PCR, the mean of two measurements at the Visit

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 Participants 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Early Bactericidal Activity (0-7)	-0.044 cell count per 1 mL of sputum Standard Deviation 0.076	-0.004 cell count per 1 mL of sputum Standard Deviation 0.081	0.116 cell count per 1 mL of sputum Standard Deviation 0.186	-0.408 cell count per 1 mL of sputum Standard Deviation 0

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA: the pharmacokinetic analysis population for multiple dosing comprised all patients participating in the PK study who had received at least one dose of the study drug PBTZ169, provided that data on study drug concentration (with at least one measurement above BLQ) was available.

Peak plasma concentration (Сmax) of PBTZ169 for multiple dosing

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Peak Plasma Concentration (Сmax) of PBTZ169	34.4714 ng/ml Standard Deviation 18.6498	122.0135 ng/ml Standard Deviation 96.3347	101.3818 ng/ml Standard Deviation 31.3830	—

SECONDARY outcome

Timeframe: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)

Population: PKA

Minimal plasma concentration (Сmin) of PBTZ169: concentration measurement following single dosing

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Minimal Plasma Concentration (Сmin) of PBTZ169	0.4985 ng/ml Standard Deviation 0.4475	0.2678 ng/ml Standard Deviation 0.3375	1.0275 ng/ml Standard Deviation 0.9101	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

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

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Residual Concentration (Ctrough) of PBTZ169 24 hours after the first dose (Ctrough_SD24)	0.7835 ng/ml Standard Deviation 0.6820	1.4116 ng/ml Standard Deviation 1.2712	1.8712 ng/ml Standard Deviation 0.9453	—
Residual Concentration (Ctrough) of PBTZ169 prior to the last dose (Ctrough_MD0)	2.1610 ng/ml Standard Deviation 1.6332	4.9505 ng/ml Standard Deviation 1.4050	18.2674 ng/ml Standard Deviation 27.2441	—
Residual Concentration (Ctrough) of PBTZ169 24 hours after the last dose (Ctrough_MD24)	1.4207 ng/ml Standard Deviation 1.0145	2.9274 ng/ml Standard Deviation 1.4535	5.2710 ng/ml Standard Deviation 2.5201	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Minimal plasma concentration (Сmin) of PBTZ169: multiple dosing

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Minimal Plasma Concentration (Сmin) of PBTZ169	1.4207 ng/ml Standard Deviation 1.0145	3.3889 ng/ml Standard Deviation 2.0001	4.9322 ng/ml Standard Deviation 2.4003	—

SECONDARY outcome

Timeframe: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)

Population: PKA

Time to reach maximum concentration (Tmax) of PBTZ169 after single oral administration in different doses

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Time to Reach Maximum Concentration (Tmax) of PBTZ169	1.250 h Interval 0.67 to 2.0	2.250 h Interval 1.0 to 6.0	2.000 h Interval 0.33 to 3.0	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Time to reach maximum concentration (Tmax) of PBTZ169 after multiple oral administration in different doses

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Time to Reach Maximum Concentration (Tmax) of PBTZ169	2.000 h Interval 0.67 to 2.98	2.000 h Interval 1.0 to 6.0	1.500 h Interval 0.0 to 2.4	—

SECONDARY outcome

Timeframe: Up to 24 hours after the first drug administration

Population: PKA

Area under the plasma concentration of PBTZ169 versus time curve in frames [0-24 hours]

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
AUC(0-24)	93.604 ng*h/ml Standard Deviation 74.3008	120.954 ng*h/ml Standard Deviation 44.7920	237.153 ng*h/ml Standard Deviation 111.4025	—

SECONDARY outcome

Timeframe: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)

Population: PKA: the pharmacokinetic analysis population for multiple dosing comprised all patients participating in the PK study who had received at least one dose of the study drug PBTZ169, provided that data on study drug concentration (with at least one measurement above BLQ) was available.

Peak plasma concentration (Сmax) of PBTZ169: concentration measurement following single dosing

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Peak Plasma Concentration (Сmax) of PBTZ169	24.6543 ng/ml Standard Deviation 18.8506	35.5370 ng/ml Standard Deviation 23.4983	79.6684 ng/ml Standard Deviation 49.1865	—

SECONDARY outcome

Timeframe: Up to 24 hours after the last drug administration

Population: PKA

Area under the plasma concentration of PBTZ169 versus time curve in frames [0-24 hours] for the last dosing (Day 14)

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
AUC(0-24)	113.293 ng*h/ml Standard Deviation 73.9862	349.308 ng*h/ml Standard Deviation 282.1627	502.895 ng*h/ml Standard Deviation 167.7201	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Area under the plasma concentration of PBTZ169 versus time curve in frames [0-last concentration above lower limit of quantification (LLoQ)]

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
AUC (0-t)	113.259 ng*h/ml Standard Deviation 73.9728	356.170 ng*h/ml Standard Deviation 282.0489	502.075 ng*h/ml Standard Deviation 168.5111	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Area under the plasma concentration versus time curve in frames [0-∞]

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
AUC(0-∞) of PBTZ169	141.855 ng*h/ml Standard Deviation 87.0391	412.819 ng*h/ml Standard Deviation 299.2734	568.581 ng*h/ml Standard Deviation 189.4584	—

SECONDARY outcome

Timeframe: 24 hours after the first and the last drug administration

Population: PKA

Accumulation ratios for the PK parameter AUC(0 -24): AUC(0- 24,ss)/AUC(0 -24), Day 1, on the original scale

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Accumulation Ratios for the PK Parameters AUC(0 -24)	1.50 ratio Interval 0.81 to 2.76	2.35 ratio Interval 1.28 to 4.34	2.74 ratio Interval 1.58 to 4.73	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Average steady-state concentration in the dosing interval following multiple dosing was evaluated as the ratio AUC0 24/τ (τ = the dosing interval)

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Average Concentration (Css,av) of PBTZ169	862.63 ng/ml Standard Deviation 606.973	793.27 ng/ml Standard Deviation 212.270	532.95 ng/ml Standard Deviation 325.436	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Fluctuations (%) in the dosing interval after multiple dosing ((Cmax - Cmin) × 100%/Css,av)

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Fluctuations (%) in the Dosing Interval	32955.25 % (ratio) Standard Deviation 18636.037	24703.16 % (ratio) Standard Deviation 19047.811	16253.19 % (ratio) Standard Deviation 7977.030	—

SECONDARY outcome

Timeframe: 24 hours after the first drug administration

Population: PKA

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.

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Total (Plasma) Clearance (Clt) of PBTZ169	3293.80 L/h Standard Deviation 3329.026	2375.06 L/h Standard Deviation 759.203	2935.49 L/h Standard Deviation 1382.371	—

SECONDARY outcome

Timeframe: 24 hours after the last drug administration

Population: PKA

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.

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Total (Plasma) Clearance (Clt) of PBTZ169	1393.31 L/h Standard Deviation 606.676	1200.61 L/h Standard Deviation 899.707	1259.77 L/h Standard Deviation 519.021	—

SECONDARY outcome

Timeframe: Up to 72 hours after the last drug administration

Population: PKA

Distribution volume Vd for a dosing interval of 72 hours after the last dose

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Volume of Distribution (Vd) of PBTZ169	4.7206 L Standard Deviation 3.0828	14.5545 L Standard Deviation 11.7568	20.9540 L Standard Deviation 6.9883	—

SECONDARY outcome

Timeframe: 24 hours after the fist drug administration

Population: PKA

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Plasma Half-life Time (T1/2) of PBTZ169	10.201 h Standard Deviation 4.6319	16.469 h Standard Deviation 9.5669	10.110 h Standard Deviation 2.1530	—

SECONDARY outcome

Timeframe: 24 hours after the last drug administration

Population: PKA

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Plasma Half-life Time (T1/2) of PBTZ169	15.524 h Standard Deviation 4.0037	13.790 h Standard Deviation 2.3234	8.883 h Standard Deviation 2.5338	—

SECONDARY outcome

Timeframe: 24 hours after the first drug administration

Population: PKA

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.

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Elimination Constant (Kel) of PBTZ169	0.0797 1/h Standard Deviation 0.0371	0.0524 1/h Standard Deviation 0.0250	0.0708 1/h Standard Deviation 0.0126	—

SECONDARY outcome

Timeframe: 72 hours after the last drug administration

Population: PKA

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.

Outcome measures

Measure	PBTZ169, 160 mg n=4 Participants 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 Participants 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=5 Participants 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Elimination Constant (Kel) of PBTZ169	0.0470 1/h Standard Deviation 0.0123	0.0515 1/h Standard Deviation 0.0098	0.0828 1/h Standard Deviation 0.0211	—

Adverse Events

PBTZ169, 160 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PBTZ169, 320 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PBTZ169, 640 mg

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Isoniazid, 600 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	PBTZ169, 160 mg n=4 participants at risk 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 participants at risk 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 participants at risk 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 participants at risk 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Gastrointestinal disorders Spontaneously opened tuberculous paraproctitis	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)

Other adverse events

Measure	PBTZ169, 160 mg n=4 participants at risk 2 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 320 mg n=4 participants at risk 4 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	PBTZ169, 640 mg n=7 participants at risk 8 capsules 80 mg of PBTZ169 once a day for 14 days PBTZ169: Once a day for 14 days	Isoniazid, 600 mg n=1 participants at risk 2 tablets 300 mg of Isoniazid once a day for 14 days Isoniazid: Once a day for 14 days
Cardiac disorders Sinus arrhythmia	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/7 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Cardiac disorders Sinus tachycardia	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Cardiac disorders Wandering atrial pacemaker	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/7 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
General disorders Hyperthermia	25.0% 1/4 • Number of events 4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/7 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations Fever	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations Metabolic disorders found in ECG	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/7 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations QTc elongation	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations QTc(F) shortening	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/7 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations Repolarization disturbances in the V1 lead in ECG	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 2 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations Reduced (+)T amplitude in standard leads	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 2 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Investigations ESR over 2.5 x normal	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Metabolism and nutrition disorders Hyperglycemia	25.0% 1/4 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/7 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)
Vascular disorders Hypotension	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/4 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	14.3% 1/7 • Number of events 1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)	0.00% 0/1 • Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1)

Additional Information

Viсtoria Shcherbakova

Nearmedic Plus

Phone: +7 (495) 741 49 89

Email: Viktoriya.Shcherbakova@nearmedic.ru

Results disclosure agreements

• Principal investigator is a sponsor employee The agreements between the Principal Investigators and the CRO restricts the PIs' rights to discuss or publish trial results after the trial is completed.
• Publication restrictions are in place

Restriction type: OTHER