Trial Outcomes & Findings for Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment (NCT NCT04874948)

NCT ID: NCT04874948

Last Updated: 2024-12-31

Results Overview

To determine the rates and routes of excretion of \[14C\]BTZ-043-related radioactivity, including mass balance of total drug-related radioactivity in urine and feces (and vomit, if applicable), following the oral administration of a single 500 mg dose of \[14C\]BTZ-043 in healthy male volunteers. All excreta were collected for the analysis for 14C quick or normal counts of total radioactivity (as feasible). the radioactivity measured was translated into mg eq (Radioactivity equivalent to 1 mg BTZ-043).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 4 participants
• Primary outcome timeframe: Urine and faeces were collected from the administration of the study medication until cumulative excretion reached 90% of total radioactivity administered. This was achieved by all subjects after 168 hours.
• Results posted on: 2024-12-31

Participant Flow

Screening started on 27th September 2021. The first participant was enrolled on October 8th, 2021. The healthy volunteers were recruited by PRA Health Sciences - Early Development Services in 9728 NZ Groningen

Participant milestones

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment

Baseline characteristics by cohort

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	22 years STANDARD_DEVIATION 3 • n=5 Participants
Sex/Gender, Customized Male	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · White + Black or African American	1 Participants n=5 Participants
Region of Enrollment Netherlands	4 participants n=5 Participants
BMI	24.3 kg/m² STANDARD_DEVIATION 4.0 • n=5 Participants
Height	177 cm STANDARD_DEVIATION 2 • n=5 Participants
Weight	75.7 kg STANDARD_DEVIATION 13.0 • n=5 Participants

PRIMARY outcome

Timeframe: Urine and faeces were collected from the administration of the study medication until cumulative excretion reached 90% of total radioactivity administered. This was achieved by all subjects after 168 hours.

Population: Per protocol

To determine the rates and routes of excretion of [14C]BTZ-043-related radioactivity, including mass balance of total drug-related radioactivity in urine and feces (and vomit, if applicable), following the oral administration of a single 500 mg dose of [14C]BTZ-043 in healthy male volunteers. All excreta were collected for the analysis for 14C quick or normal counts of total radioactivity (as feasible). the radioactivity measured was translated into mg eq (Radioactivity equivalent to 1 mg BTZ-043).

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Rates and Routes of Excretion total drug-related radioactivity in faeces	162 mg eq Standard Deviation 23.0
Rates and Routes of Excretion total drug-related radioactivity in urine	331 mg eq Standard Deviation 23.2

PRIMARY outcome

Timeframe: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

Population: per protocol

To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Pharmacokinetics of Total Radioactivity in Blood and Plasma (Cmax) Cmax Plasma	8730 ng eq/mL Standard Deviation 2550
Pharmacokinetics of Total Radioactivity in Blood and Plasma (Cmax) Cmax Blood	4970 ng eq/mL Standard Deviation 1370

PRIMARY outcome

Timeframe: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

Population: per protocol

To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Pharmacokinetics of Total Radioactivity in Blood and Plasma (AUC-t) AUC-t Plasma	125000 h*ng eq/mL Standard Deviation 26900
Pharmacokinetics of Total Radioactivity in Blood and Plasma (AUC-t) AUC-t Blood	76700 h*ng eq/mL Standard Deviation 18500

PRIMARY outcome

Timeframe: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

Population: per protocol. On participant excluded as value was justed unreliable

To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=3 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Pharmacokinetics of Total Radioactivity in Blood (T1/2)	158 h Standard Deviation 24.7

PRIMARY outcome

Timeframe: Blood samples for total radioactivity were collected from day 1 until 168 h post dosing

Population: per protocol.

To determine the pharmacokinetics (PK) of total radioactivity in whole blood and in plasma. Measured radioactivity was translated into ng equivalent of BTZ-043. Based on the ng eq, pharmacokinetic parameters were calculated.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Pharmacokinetics of Total Radioactivity in Plasma (T1/2)	186 h Standard Deviation 18.9

PRIMARY outcome

Timeframe: Day 1 to Day 3

Population: Per protocol

To characterize the plasma PK of BTZ-043 and main metabolites by liquid chromatography-mass spectrometry (LC-MS), if applicable. BTZ-043 is metabolized in the human body. Some of the metabolites were known prior to this study like the main metabolite M2, a hydrid Meisenheimer complex or the aminometabolite M1. Metabolite M4 and M10 were known before as well, therefore, the bioanalytical methods mentioned above could be developed and validated for these metabolites.Pharmacokinetic parameters are calculated from the individual plasma level measurements.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Plasma PK of BTZ-043 and Main Metabolites (Cmax) Cmax BTZ-043	1600 ng/mL Standard Deviation 509
Plasma PK of BTZ-043 and Main Metabolites (Cmax) Cmax M1	163 ng/mL Standard Deviation 27.5
Plasma PK of BTZ-043 and Main Metabolites (Cmax) Cmax M2	5180 ng/mL Standard Deviation 1310
Plasma PK of BTZ-043 and Main Metabolites (Cmax) Cmax M4total	1190 ng/mL Standard Deviation 455
Plasma PK of BTZ-043 and Main Metabolites (Cmax) Cmax M10	30.6 ng/mL Standard Deviation 6.50

PRIMARY outcome

Timeframe: Day 1 to Day 3

Population: Per protocol

To characterize the plasma PK of BTZ-043 and main metabolites by liquid chromatography-mass spectrometry (LC-MS), if applicable. BTZ-043 is metabolized in the human body. Some of the metabolites were known prior to this study like the main metabolite M2, a hydrid Meisenheimer complex or the aminometabolite M1. Metabolite M4 and M10 were known before as well, therefore, the bioanalytical methods mentioned above could be developed and validated for these metabolites. Pharmacokinetic parameters are calculated from the individual plasma level measurements.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Plasma PK of BTZ-043 and Main Metabolites (AUC-last) AUClast BTZ-043	3920 h*ng/mL Standard Deviation 842
Plasma PK of BTZ-043 and Main Metabolites (AUC-last) AUClast M1	2710 h*ng/mL Standard Deviation 433
Plasma PK of BTZ-043 and Main Metabolites (AUC-last) AUClast M2	41000 h*ng/mL Standard Deviation 6220
Plasma PK of BTZ-043 and Main Metabolites (AUC-last) AUClast M4total	10300 h*ng/mL Standard Deviation 3990
Plasma PK of BTZ-043 and Main Metabolites (AUC-last) AUClast M10	505 h*ng/mL Standard Deviation 199

PRIMARY outcome

Timeframe: Day 1 to Day 3

Population: Per protocol

To characterize the plasma PK of BTZ-043 and main metabolites by liquid chromatography-mass spectrometry (LC-MS), if applicable. BTZ-043 is metabolized in the human body. Some of the metabolites were known prior to this study like the main metabolite M2, a hydrid Meisenheimer complex or the aminometabolite M1. Metabolite M4 and M10 were known before as well, therefore, the bioanalytical methods mentioned above could be developed and validated for these metabolites. Pharmacokinetic parameters are calculated from the individual plasma level measurements.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Plasma PK of BTZ-043 and Main Metabolites (t1/2) T1/2 BTZ-043	2.43 h Standard Deviation 1.01
Plasma PK of BTZ-043 and Main Metabolites (t1/2) T1/2 M1	8.65 h Standard Deviation 0
Plasma PK of BTZ-043 and Main Metabolites (t1/2) T1/2 M2	4.90 h Standard Deviation 0.591
Plasma PK of BTZ-043 and Main Metabolites (t1/2) T1/2 M4total	3.83 h Standard Deviation 0.281
Plasma PK of BTZ-043 and Main Metabolites (t1/2) T1/2 M10	18.9 h Standard Deviation 10.2

PRIMARY outcome

Timeframe: Assessed from time of dosing up to 168 h post dose. BTZ-043 and metabolites were excreted fom 0 - 24 h (BTZ-043 and M1) and from 0 - 48 h (M2, M4 total and M10 total).

Population: Per protocol

Urine volume was measured after every micturation and hamilton pools have been prepared for analysis of BTZ-043 and main metabolites by LC-MS. BTZ-043 could only be measured in urine within the first 24h, then no additional BTZ-043 was excreted in urine anymore. The same applies for M1. M2, M4 total and M10 total excretion could be measured in urine up to 48h post dose.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Urine Concentrations of BTZ-043 and Main Metabolites BTZ-043 (M0) Cumulative Amount Excreted 0 - 24h	8.83 mg eq Standard Deviation 4.51
Urine Concentrations of BTZ-043 and Main Metabolites M1 Cumulative Amount Excreted 0 - 24h	1.53 mg eq Standard Deviation 0.518
Urine Concentrations of BTZ-043 and Main Metabolites M2 Cumulative Amount Excreted 0 - 24h	53.9 mg eq Standard Deviation 17.1
Urine Concentrations of BTZ-043 and Main Metabolites M2 Cumulative Amount Excreted 0 - 48h	54.7 mg eq Standard Deviation 17.3
Urine Concentrations of BTZ-043 and Main Metabolites M4 total Cumulative Amount Excreted 0 - 24h	59.4 mg eq Standard Deviation 9.77
Urine Concentrations of BTZ-043 and Main Metabolites M4 total Cumulative Amount Excreted 0 - 48h	60.5 mg eq Standard Deviation 10.2
Urine Concentrations of BTZ-043 and Main Metabolites M10 total Cumulative Amount Excreted 0 - 24h	2.47 mg eq Standard Deviation 1.33
Urine Concentrations of BTZ-043 and Main Metabolites M10 total Cumulative Amount Excreted 0 - 48h	2.65 mg eq Standard Deviation 1.45
Urine Concentrations of BTZ-043 and Main Metabolites Sum(M0, M1, M2, M4total, M10) Cumulative Amount Excreted 0-24h	126 mg eq Standard Deviation 15.7
Urine Concentrations of BTZ-043 and Main Metabolites Sum(M0, M1, M2, M4total, M10) Cumulative Amount Excreted 0-48h	128 mg eq Standard Deviation 16.4

SECONDARY outcome

Timeframe: Day -1 to day 32

Population: Received at least one dose of BTZ-043

To assess the safety and tolerability of a single 500 mg oral dose of BTZ-043 administered to healthy volunteers.

Outcome measures

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 Participants 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Number of Adverse Events	6 Adverse Events

Adverse Events

Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Single Oral Administration of 500 mg BTZ-043 Containing 3.7 MBq of [14C]BTZ-043 n=4 participants at risk 4 subjects to receive a single oral administration of 14C-labeled radioactive 500mg BTZ-043 containing 3.7 MBq of \[14C\]BTZ-043
Nervous system disorders Dizziness	100.0% 4/4 • Number of events 4 • Day -1 (admission) until follow-up on day 31 or 32 An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. AE definitions according to ICH topic E2A. All AEs reported or apparent from their physical appearance during the clinical study were reported on the AE eCRF page. Severity of AEs was graded using the most current version of the MedDRA
Nervous system disorders Somnolence	25.0% 1/4 • Number of events 1 • Day -1 (admission) until follow-up on day 31 or 32 An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. AE definitions according to ICH topic E2A. All AEs reported or apparent from their physical appearance during the clinical study were reported on the AE eCRF page. Severity of AEs was graded using the most current version of the MedDRA
Infections and infestations Oral Herpes	25.0% 1/4 • Number of events 1 • Day -1 (admission) until follow-up on day 31 or 32 An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. AE definitions according to ICH topic E2A. All AEs reported or apparent from their physical appearance during the clinical study were reported on the AE eCRF page. Severity of AEs was graded using the most current version of the MedDRA

Additional Information

Dr. med. vet. Julia Dreisbach

Klinikum der Universität München (LMU)

Phone: +49 89 4400

Email: julia.dreisbach@med.uni-muenchen.de

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60