Clinical trial NCT05526911
Conditions: Pulmonary Disease Tuberculosis, Pulmonary Tuberculosis Multi Drug Resistant Tuberculosis Drug Sensitive Tuberculosis Drug-resistant Tuberculosis Mycobacterium Tuberculosis Infection
Keywords: TBAJ-876 Diarylquinoline DARQ
Sponsor: Global Alliance for TB Drug Development
Start date: 2022-06-30; Completion date: 2022-09-26
Enrollment: 28 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the Induction Potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition Potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects

Detailed description:
This study was a two-part, open-label drug-drug interaction study conducted in one study center in the United States. Two groups were planned, Group 1 and Group 2. Group 2 to be conducted based on the Group 1 results.

Group 1 to assess the induction potential of TBAJ-876 on the sensitive CYP3A4 substrate midazolam (M) and inhibition and induction potential of TBAJ-876 on the sensitive P-glycoprotein substrate Digoxin (D).

Group 2 was only to be conducted if the results of Group 1 show that TBAJ-876 is a moderate inducer of either CYP3A4 (geometric mean ratio \[GMR\] of midazolam area under the curve \[AUC\] \<0.50 when co-administered with TBAJ-876) or P-glycoprotein (GMR of digoxin AUC \<0.50 when co-administered with TBAJ-876) or a moderate inhibitor of P-glycoprotein (GMR of digoxin AUC ≥2.0 when co-administered with TBAJ-876). These results were used to decide that a second phase of the study was not needed.

If Group 1 concluded that TBAJ-876 is a moderate inducer or inhibitor, Group 2 had intended to quantify the magnitude of inhibition or induction of TBAJ-876 of the antiretroviral regimen TLD, a fixed dose combination of tenofovir disoproxil fumarate (TFD), lamivudine (3TC) and dolutegravir (DTG), a regimen likely to be used in future clinical studies of TBAJ-876 by subjects living with HIV

Safety was assessed throughout the study for all subjects. Safety assessments included physical examinations, vital signs, serial ECGs, adverse events (AEs), clinical and laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).

Arms: arm 1: The pharmacokinetics of midazolam, a CYP3A4 substrate, and digoxin, a P-gp substrate, will be studied before and after dosing with TBAJ-876.
Interventions: intervention 1: TBAJ-876 intervention 2: Midazolam intervention 3: Digoxin
Intervention descriptions: intervention 1: * Day 6 to Day 13: 200 mg TBAJ-876 oral suspension, fed
* Day 14 to Day 19: 165 mg TBAJ-876 oral suspension, fed
* Day 20 and Day 21: 200 mg TBAJ-876 oral suspension, fasting
* Day 22 to Day 24: 150 mg TBAJ-876 oral suspension, fed intervention 2: Day 1 and Day 20: Midazolam oral syrup: 2 mg, fasted intervention 3: Day 2 and Day 21: Digoxin tablet: 0.25 mg, fasted

Protocol documents:
Prot_000.pdf: 
 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
29-July-2022 
 
Page 1 of 6 
PROTOCOL CLARIFICATION LETTER (29 July 2022) 
 
 
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the 
Induction potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition 
potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects 
 
 
TB Alliance PROTOCOL NO. TBAJ-876-CL002 
TKL STUDY NO. P1980322 
Version 1.0 
Dated: 20-May-2022 
 
 
 
The purpose of this protocol clarification letter is to update vital signs footnote, exclusion criteria, 
PK sampling time windows, Section 7.6.3 Vital Signs, and Section 7.6.5 Electrocardiograms. 
 
 
 
 
 
Antonio (Tony) Lombardi, MD 
Medical Officer 
Signature  
 
Date 
 
 
 
Suraj Saggar, MD 
Principal Investigator 
 
Signature  
 Date 
 
 
 
Irina Krause, RN, MSN 
Senior Director, Phase I Operations 
 
Signature  
 Date 
 
 
8/1/2022
7/29/2022
7/30/2022


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
29-July-2022 
 
Page 2 of 6 
1. Updated Footnote g 
Current footnote per PCL dated 13-July-2022: 
g. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be 
measured at screening, and check-in (Day -1). 
Furthermore, vital signs should also be taken once daily on Days 3-5, Days 7 - 19 (6 hours post dose on 
dosing days and around the same time on non-dosing days), Day 22-Day 23 (6 hours after Dosing) and Day 
25 (prior to discharge) or early withdrawal (vital signs must be done within 15 minutes before review of 
medication and collection of adverse experiences). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the 
defined time points in flowchart at study hours pre-dose, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24. 
Orthostatic blood pressure and heart rate should be measured at study hours pre-dose, 2, 6 and 12 on Days 1, 
2, 6, 20, 21 and 24, after subjects are in supine position for at least 2 minutes and then again after standing 
for at least 1 minute), except when they are supine or semi-reclined because of study procedures and/or 
adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
 
Revised footnote: 
g. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be 
measured at screening, and check-in (Day -1). 
Furthermore, vital signs should also be taken once daily on Days 3-5, Days 7 - 19 (6 hours post dose on 
dosing days and around the same time on non-dosing days), Day 22-Day 23 (6 hours after Dosing) and Day 
25 (prior to discharge) or early withdrawal (vital signs must be done within 15 minutes before review of 
medication and collection of adverse experiences review). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the 
defined time points in flowchart at study hours pre-dose, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24. 
Orthostatic blood pressure and heart rate should be measured at study hours pre-dose, 2, 6 and 12 on Days 1, 
2, 6, 20, 21 and 24, after subjects are in supine position for at least 2 minutes and then again after standing 
for at least 1 minute), except when they are supine or semi-reclined because of study procedures and/or 
adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
 
2. Updated Exclusion Language (Exclusion Section 5.2) 
Current Exclusion #9:  
9. Subjects with the following laboratory abnormalities at screening or Day -1: 
a. ALT or AST >1.0 times upper limit of normal (ULN) 
b. Creatinine grade 2 or greater (>1.5 times ULN) 
c. Total lipase or amylase >1.0 times ULN 
d. Total bilirubin grade 1 or greater (>1.0 times ULN) 
e. CPK >1.25 times ULN 
If exclusionary lab criteria are met, values may be confirmed by repeat evaluation. 
Revised Exclusion #9: 
9. Subjects with the following laboratory abnormalities at screening or Day -1:  


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
29-July-2022 
 
Page 3 of 6 
a. ALT or AST grade 2 or greater (≥2.0 times upper limit of normal ULN) 
b. Creatinine grade 2 or greater (≥1.6 times ULN) 
c. Total lipase or amylase ≥1.6 times ULN 
d. Total bilirubin grade 2 or greater (≥1.5 times ULN) 
e. CPK >1.25 times ULN 
f. Glomerular Filtration Rate (eGFR) <60 ml/min/1.73m2 
 
If exclusionary lab criteria are met, values may be confirmed by repeat evaluation. 
 
Current Exclusion #13: 
13. 
Heart rate is lower than 60 beats per minute (bpm) or higher than 100 bpm at screening, Day 
-1 (check-in), or pre-dose. Out of range vital signs may be repeated once for confirmation. Out of 
range values will not be considered AEs if the repeat assessment is in range. 
 
Revised Exclusion #13: 
13. 
Clinically significant heart rate abnormalities such as heart rate is lower than 60 beats 
per minute (bpm) or higher than 100 bpm at screening, Day -1 (check-in), or pre-dose. Out of range 
vital signs may be repeated once for confirmation. Out of range values will not be considered AEs 
if the repeat assessment is in range.  
 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
29-July-2022 
 
Page 4 of 6 
3. Updated Table 7 Acceptable Pharmacokinetic Sampling Time Windows 
Current Table 7: 
Table 1 
Acceptable Pharmacokinetic Sampling Time Windows 
 
Investigation and 
Examination 
Allowable Time Window 
 
Pre-dose 
0-24 hours 
>24 hours to Day 
25 
Plasma sample 
collection for 
pharmacokinetic 
assessment 
Within 1 hour pre-
dose 
 
+- 5 minutes 
+- 15 minutes 
 
Revised Table 7: 
Table 2 
Acceptable Pharmacokinetic Sampling Time Windows 
 
Investigation and 
Examination 
Allowable Time Window 
 
Pre-dose 
Timepoints 
0-24 hours 
Timepoints >24 
hours to Day 25 
Plasma sample 
collection for 
pharmacokinetic 
assessment 
Within 1 hour pre-
dose 
 
+- 5 minutes 
+- 15 minutes 
 
4. Updated Section 7.6.3 Vital Signs 
Current wording per PCL dated 23-June-2022: 
Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) 
should be measured at screening, and check-in, Day -1.  
Furthermore, vital signs should also be taken once daily on Day 3-5, 7 through Day 19 (6 hours post 
dose on dosing days and around the same time on non-dosing days), Day 22-Day 23 (6 hours after 
Dosing) and Day 25 (prior to discharge) or early withdrawal (vital signs must be done within 15 
minutes before review of medication and collection of adverse experiences). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes 
of the defined time points in flowchart at study hours pre-dose, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 
20, 21, and 24.  
Orthostatic blood pressure and heart rate should be measured at study hours Pre-dose, 2, 6 and 12 
on Days 1, 2, 6, 20, 21 and 24, after subjects are in supine position for at least 2 minutes and then 
again after standing for at least 1 minute), except when they are supine or semi-reclined because of 
study procedures and/or adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
29-July-2022 
 
Page 5 of 6 
Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) 
should be measured at screening, and check-in, Day -1.  
Furthermore, vital signs should also be taken once daily on Day 3-5, 7 through Day 19 (6 hours post 
dose on dosing days and around the same time on non-dosing days), Day 22-Day 23 (6 hours after 
Dosing) and Day 25 (prior to discharge) or early withdrawal (vital signs must be done within 15 
minutes before review of medication and collection of adverse experiences review). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes 
of the defined time points in flowchart at study hours pre-dose, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 
20, 21, and 24.  
Orthostatic blood pressure and heart rate should be measured at study hours Pre-dose, 2, 6 and 12 
on Days 1, 2, 6, 20, 21 and 24, after subjects are in supine position for at least 2 minutes and then 
again after standing for at least 1 minute), except when they are supine or semi-reclined because of 
study procedures and/or adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
 
5. Updated Section 7.6.5 Electrocardiograms 
Current Wording: 
Group 1 
 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 3, 7, 20, 21, 22 and on Day 25 or 
upon early withdrawal. The pre-dose ECG should be completed within 20 minutes prior to the pre-
dose blood draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline 
QTcF >60 ms, after repeat testing, additional ECGs should be recorded until normalization or return 
to baseline. 
 
Group 2 
 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 7, 20, 21 and 25 or upon early 
withdrawal. The pre-dose ECG should be completed within 20 minutes prior to the pre-dose blood 
draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline QTcF >60 
ms, after repeat testing, additional ECGs should be recorded until normalization or return to baseline. 
 
Revised Wording: 
Group 1 
 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 3, 7, 20, 21, 22 and on Day 25 or 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
29-July-2022 
 
Page 6 of 6 
upon early withdrawal. The pre-dose ECG should be completed within at least 20 minutes prior to 
the pre-dose blood draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-
baseline QTcF >60 ms, after repeat testing, additional ECGs should be recorded until normalization 
or return to baseline. 
 
Group 2 
 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 7, 20, 21 and 25 or upon early 
withdrawal. The pre-dose ECG should be completed within at least 20 minutes prior to the pre-dose 
blood draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline 
QTcF >60 ms, after repeat testing, additional ECGs should be recorded until normalization or return 
to baseline. 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
13-July-2022 
 
Page 1 of 5 
PROTOCOL CLARIFICATION LETTER (13 July 2022) 
 
 
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the 
Induction potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition 
potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects 
 
 
TB Alliance PROTOCOL NO. TBAJ-876-CL002 
TKL STUDY NO. P1980322 
Version 1.0 
Dated: 20-May-2022 
 
 
 
The purpose of this protocol clarification letter is to update vital signs footnote, exclusion criteria, 
and administration of TBAJ-876 oral suspension language.  
 
 
 
 
 
Antonio (Tony) Lombardi, MD 
Medical Officer 
Signature  
 
Date 
 
 
 
Suraj Saggar, MD 
Principal Investigator 
 
Signature  
 Date 
 
 
 
Irina Krause, RN, MSN 
Senior Director, Phase I Operations 
 
Signature  
 Date 
 
 
7/13/2022
7/13/2022
7/15/2022


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
13-July-2022 
 
Page 2 of 5 
1. Updated the Schedule of Assessments & Procedures, Group 1: Midazolam, Digoxin 
Table, Section 1.2 Flow Chart; Footnotes a, d, g 
Current footnotes per PCL dated 23-June-2022: 
a. 
Confinement to start at check-in (Evening of Day 1) until 24 hours after dosing on Day 25. 
 
d. Safety laboratory assessments. The following analyses will be performed at the following timepoints: Screening, 
Day -1, Day 2, Day 3, Day 7, Day 20, Day 21, Day 22, and Day 25. 
• 
Hematology: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell (RBC) 
count, reticulocyte count, and platelet count. 
• 
Coagulation Tests: Activated partial thromboplastin time (aPTT2), Prothrombin time (PT2) 
• 
Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK), 
direct, indirect, and total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), sodium (Na+), potassium (K+), chloride (CL-), lactate dehydrogenase 
(LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and bicarbonate, lipase, and amylase 
• 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN), according to FDA guidance 
criteria (see Appendix 3), the following tests should be performed: creatine phosphokinase of 
myocardial band (CPK-MB) and cardiac troponin T I.  
• 
Urinalysis: The following will be evaluated by an automated or manual urine “dipstick” method: pH, 
specific gravity, protein, glucose, ketones, bilirubin, creatinine, nitrite, sodium, urobilinogen, blood, 
myoglobin, leukocyte esterase. If protein, occult blood, nitrate, or leukocyte esterase values are out of 
range, a microscopic examination will be performed.  Myoglobin will be collected but results will not 
be required for dose qualification. 
• 
Urine Drug, Cotinine, and Alcohol Breathalyzer Screens - Urine samples will be tested for drugs of 
abuse (amphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, opiates) cotinine, and 
alcohol at screening and check-in only. 
 
g. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be 
measured at screening, and check-in (Day -1). 
Furthermore, vital signs should also be taken once daily on Days 3-5, Days 7 - 19 (6 hours post dose on dosing 
days and around the same time on non-dosing days), Day 22-Day 23 (6 hours after Dosing) and Day 25 (prior 
to discharge) or early withdrawal (vital signs must be done within 15 minutes before review of medication and 
collection of adverse experiences). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the 
defined time points in flowchart at study hours pre-dose, 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 
24.  
Orthostatic blood pressure and heart rate should be measured at study hours pre-dose, 2, 6 and 12 time points 
on Days 1, 2, 6, 20, 21 and 24, after subjects are in supine position for at least 2 minutes and then again after 
standing for at least 1 minute), except when they are supine or semi-reclined because of study procedures 
and/or adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
 
Revised footnotes: 
a. 
Confinement to start at check-in (Evening of Day -1) until 24 hours after dosing on Day 24. 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
13-July-2022 
 
Page 3 of 5 
d. Safety laboratory assessments. The following analyses will be performed at the following timepoints: 
Screening, Day -1, Day 2, Day 3, Day 7, Day 20, Day 21, Day 22, and Day 25. 
• 
Hematology: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell (RBC) 
count, reticulocyte count, and platelet count. 
• 
Coagulation Tests: Activated partial thromboplastin time (aPTT2), Prothrombin time (PT2) 
• 
Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK), 
direct, indirect, and total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), sodium (Na+), potassium (K+), chloride (CL-), lactate dehydrogenase 
(LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and bicarbonate, lipase, and amylase 
• 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN), according to FDA guidance 
criteria (see Appendix 3), the following tests should be performed: creatine phosphokinase of 
myocardial band (CPK-MB) and cardiac troponin T I.  
• 
Urinalysis: The following will be evaluated by an automated or manual urine “dipstick” method: pH, 
specific gravity, protein, glucose, ketones, bilirubin, creatinine, nitrite, sodium, urobilinogen, blood, 
myoglobin, leukocyte esterase. If protein, occult blood, nitrate, or leukocyte esterase values are out of 
range, a microscopic examination will be performed.  Myoglobin will be collected but results will not 
be required for dose qualification. 
• 
Urine Drug, Urine Cotinine, and Alcohol Breathalyzer Screens - Urine samples will be tested for drugs 
of abuse (amphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, opiates) and cotinine, 
in conjunction with an alcohol breathalyzer., and alcohol  These tests will be performed at 
screening and check-in only. 
 
g. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be 
measured at screening, and check-in (Day -1). 
Furthermore, vital signs should also be taken once daily on Days 3-5, Days 7 - 19 (6 hours post dose on 
dosing days and around the same time on non-dosing days), Day 22-Day 23 (6 hours after Dosing) and Day 
25 (prior to discharge) or early withdrawal (vital signs must be done within 15 minutes before review of 
medication and collection of adverse experiences). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the 
defined time points in flowchart at study hours pre-dose, 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 
24. 
Orthostatic blood pressure and heart rate should be measured at study hours pre-dose, 2, 6 and 12 on Days 1, 
2, 6, 20, 21 and 24, after subjects are in supine position for at least 2 minutes and then again after standing 
for at least 1 minute), except when they are supine or semi-reclined because of study procedures and/or 
adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
2. Updated Exclusion Language (Exclusion Section 5.2) 
Current Exclusion #15 per PCL dated 23-June-2022:  
15. 
QTcF interval >450 ms for males or >470 ms for females at screening, Day -1, or Day 2 (pre-
dose), or history of prolonged QT syndrome. PR interval < 200 ms at screening, Day -1, or Day 2 
pre-dose. Out of range values may be repeated twice for confirmation. The average QTcF or PR 
intervals of the three ECG recordings will be used to determine qualification. 
Revised Exclusion #15: 
15. 
QTcF interval >450 ms for males or >470 ms for females at screening, Day -1, or Day 2 (pre-
dose), or history of prolonged QT syndrome. PR interval > 200 ms at screening, Day -1, or Day 2 
pre-dose. Out of range values may be repeated twice for confirmation. The average QTcF or PR 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
13-July-2022 
 
Page 4 of 5 
intervals of the three ECG recordings will be used to determine qualification. 
3. Administration of TBAJ-876 Oral Suspension, Section 6.1 
Current Wording: 
Note: Detailed instructions for preparing and dispensing TBAJ-876 Oral Suspension will be 
provided in a separate pharmacy manual. Any instructions in the pharmacy manual shall supersede 
those presented in this protocol. 
TBAJ-876 Oral Suspension will be transferred and stored in Pyrex glass reagent bottles with a 
polypropylene (PP) screw cap without a liner. These bottles will be used for mixing, sampling, and 
storage prior to administration. 
The required doses of the drug product will be dispensed using commercially available oral syringes 
of suitable capacity. The suspension will be dispensed just prior to dosing and not stored in the oral 
syringes. 
Refer to Appendix 2: Description and Composition of Investigational Medicinal Product (IMP) for 
details. 
Each dose of TBAJ-876 Oral Suspension will be administered orally followed by approximately 
240 mL of room temperature water. A mouth check will be performed immediately after dose to 
ensure that the medication has been appropriately swallowed. 
Subjects will remain seated, except as otherwise required for study procedures or personal needs, for 
the first 4 hours after dosing. Should the need to move about occur during the first 4 hours after dosing 
on these days, subjects may be escorted to such procedures or activities by research personnel as 
deemed medically necessary. Subjects will not be allowed to lie down, except as directed by clinical 
staff secondary to AEs, for the first 4 hours after dosing. 
Revised Wording: 
Note: Detailed instructions for preparing and dispensing TBAJ-876 Oral Suspension will be 
provided in a separate pharmacy manual. Any instructions in the pharmacy manual shall supersede 
those presented in this protocol. 
TBAJ-876 Oral Suspension will be transferred and stored in Pyrex glass reagent bottles with a 
polypropylene (PP) screw cap without a liner. These bottles will be used for mixing, sampling, and 
storage prior to administration. 
The required doses of the drug product will be dispensed using commercially available oral 
syringes of suitable capacity. The suspension will be dispensed just prior to dosing and not 
stored in the oral syringes. 
Refer to Appendix 2: Description and Composition of Investigational Medicinal Product (IMP) for 
details. 
Each dose of TBAJ-876 Oral Suspension will be administered orally followed by approximately 
240 mL of room temperature water. The TBAJ-876 doses from the oral syringes may be 
transferred to a dosing container for the subjects to swallow. The dosing container will be 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
13-July-2022 
 
Page 5 of 5 
rinsed with a portion of the approximately 240 mL of water, swallowed by the subject and 
followed by the remainder of the approximately 240 mL water. A mouth check will be 
performed immediately after dose to ensure that the medication has been appropriately swallowed. 
Subjects will remain seated, except as otherwise required for study procedures or personal needs, for 
the first 4 hours after dosing. Should the need to move about occur during the first 4 hours after dosing 
on these days, subjects may be escorted to such procedures or activities by research personnel as 
deemed medically necessary. Subjects will not be allowed to lie down, except as directed by clinical 
staff secondary to AEs, for the first 4 hours after dosing. 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 1 of 21 
PROTOCOL CLARIFICATION LETTER (23 June 2022) 
 
 
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the 
Induction potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition 
potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects 
 
 
TB Alliance PROTOCOL NO. TBAJ-876-CL002 
TKL STUDY NO. P1980322 
Version 1.0 
Dated: 20-May-2022 
 
 
 
The purpose of this protocol clarification letter is to update the schedule of assessments and 
accompanying footnotes, inclusion/exclusion criteria, restrictions, check-in procedures, laboratory 
parameters, vital signs language, physical examination language, electrocardiograms language, PK 
processing instructions, plasma processing instructions, and tables for cardiovascular and laboratory 
abnormalities.  
 
 
 
 
 
Antonio (Tony) Lombardi, MD 
Medical Officer 
Signature  
 
Date 
 
 
 
Suraj Saggar, MD 
Principal Investigator 
 
Signature  
 Date 
 
 
 
Irina Krause, RN, MSN 
Senior Director, Phase I Operations 
 
Signature  
 Date 
 
 
June 23, 2022 | 2:37 PM PDT
June 24, 2022 | 7:33 AM EDT
June 24, 2022 | 12:27 PM EDT


 
                                                                            Protocol Clarification Letter, v1.0 
 
 
 
 
TBAJ-876-CL002 
 
 
 
 
       23-June-2022 
 
Page 2 of 21 
1. Updated the Schedule of Assessments & Procedures, Group 1: Midazolam, Digoxin Table, Section 1.2 Flow Chart 
Current Table and Footnotes: 
Table 1.2.1: Schedule of Assessments & Procedures, Group 1: Midazolam, Digoxin 
 
SCR 
CHECK-
IN 
TREATMENT 
CHECK-
OUT 
FOLLOW UP  
 
DAY 
-21 
to -1 
-1 
1 
2-5 
 
6-16 
17 
18 
19 
20 
21 
22-24 
25  
32 
EARLY 
WITHDRAWAL 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check-in 
questions 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, 
BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV/ Hepatitis 
B, C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
pregnancy testb 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
FSHb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine 
drug/alcohol/ 
cotinine screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Labs 
hematology, 
chemistry, 
urinalysis)c 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Coagulationc 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Physical exam 
X 
X 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Heart Murmurd  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Vital signs 
(blood pressure, 
pulse, 
temperature, 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 


 
                                                                            Protocol Clarification Letter, v1.0 
 
 
 
 
TBAJ-876-CL002 
 
 
 
 
       23-June-2022 
 
Page 3 of 21 
 
SCR 
CHECK-
IN 
TREATMENT 
CHECK-
OUT 
FOLLOW UP  
 
DAY 
-21 
to -1 
-1 
1 
2-5 
 
6-16 
17 
18 
19 
20 
21 
22-24 
25  
32 
EARLY 
WITHDRAWAL 
respiration rate, 
and pulse 
oximetry)e 
Concomitant 
medication 
reviewf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Midazolam 
Doseh 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Digoxin Dosei 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
TBAJ-876j 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
12-lead safety 
ECGsk 
 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Plasma for PKl 
 
 
X 
X 
 
X 
 
 
X 
X 
X 
X 
 
 
SCR=screening; ECG = electrocardiogram; FSH = follicle-stimulating hormone; FU = follow up; HIV = human immunodeficiency virus; N/A = not 
applicable; PK = pharmacokinetic; SCR = screening 
a. 
Confinement to start at check-in (Evening of Day 1) until 24 hours after dosing on Day 25. 
b. Serum pregnancy test done at screening, check-in, and Day 25 for females only. FSH completed for perimenopausal females only. 
c. 
Safety laboratory assessments. The following analyses will be performed at the following timepoints: Screening, Day -1, Day 2, Day 3, Day 7, 
Day 20, Day 21, Day 22, and Day 25. 
 
• 
Hematology: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell (RBC) count, reticulocyte count, and platelet 
count. 
• 
Coagulation Tests: Activated partial thromboplastin time (aPTT2), Prothrombin time (PT2) 
• 
Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK), direct, indirect, and total bilirubin, 
alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium (Na+), potassium (K+), 
chloride (CL-), lactate dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and bicarbonate, lipase, and 
amylase 
• 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN), according to FDA guidance criteria (see Appendix 3), the 
following tests should be performed: creatine phosphokinase of myocardial band (CPK-MB), trypsin like immunoreactivity, and 
cardiac troponin I.  


 
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       23-June-2022 
 
Page 4 of 21 
• 
Urinalysis: The following will be evaluated by an automated or manual urine “dipstick” method: pH, specific gravity, protein, glucose, 
ketones, bilirubin, creatinine, nitrite, sodium, urobilinogen, blood, myoglobin, leukocyte esterase. If protein, occult blood, nitrate, or 
leukocyte esterase values are out of range, a microscopic examination will be performed.  Myoglobin will be collected but results will 
not be required for dose qualification. 
• 
Urine Drug, Cotinine, and Alcohol Screens - Urine samples will be tested for drugs of abuse (amphetamines, benzodiazepines, 
barbiturates, cannabinoids, cocaine, opiates) cotinine, and alcohol. 
d. Heart murmur: Presence of heart murmur 
e. 
Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be measured at screening, and check-in, 
Day -1. Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the defined time points in flowchart 
at study hours 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24. Furthermore, vital signs should also be taken once daily on Day 7 through 
Day 20 (6 hours after Dosing) and Day 25 or early withdrawal (must be done within 15 minutes before review of medication and collection of 
adverse experiences). Both blood pressure and heart rate should be captured simultaneously. Blood pressure and heart rate should be measured 
after subjects are in supine position for at least 2 minutes and then again after standing for at least 1 minute (starting with 2-hr post dose VS), 
except when they are supine or semi-reclined because of study procedures and/or adverse events, or as deemed necessary by the Investigator. 
f. 
On Day 32, follow-up questioning on concomitant medications will be completed by a phone call. 
g. Adverse events to be monitored from the time of informed consent signing throughout the study via safety assessments, observation, and 
participant reporting. Specific adverse event questions will be posed daily throughout the study until Day 25 and a follow-up phone call on Day 
32. 
h. Midazolam Dose on Day 1 and Day 20 under fasted conditions 
i. 
Digoxin Dose on Day 2 and Day 21 under fasted conditions 
j. 
TBAJ-876 will be dosed as following: 
a. 200 mgTBAJ-876 on Day 6 - 13 under fed conditions 
b. 165 mg TBAJ-876 on Day 14 – 19 under Fed conditions 
c. 
200 mg TBAJ-876 on Day 20 - 21 under fasted conditions 
d. 150 mg TBAJ-876 on Day 22 - 24 under fed conditions 
k. 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or designee. Single ECGs will be completed at 
screening, Day -1, 2, 3, 7, 20, 21, 22 on Day 25 or upon early withdrawal. Furthermore, ECGs should also be taken on Digoxin dosing 
days, on Day 2 and Day 21, at study hours 0, 0.5, 1, 2, 6, and 12 within 15 minutes of the defined time points. The pre-dose ECG should be 
completed within 90 minutes prior to dosing and all ECGs should be completed prior to blood draws. If a participant experiences a post-dosing 
QTcF >500 ms or a change-from-baseline QTcF >60 ms, after repeat testing, additional ECGs should be recorded until normalization or return 
to baseline 
l. 
Blood plasma samples will be drawn at the following timepoints: 
• 
Midazolam: Day 1 and Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours 
• 
TBAJ-876: Day 17: pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24 hours 
• 
Digoxin:  
o 
Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 3), 48 (D4), 72 (D5), 96 (D6) hours 


 
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TBAJ-876-CL002 
 
 
 
 
       23-June-2022 
 
Page 5 of 21 
o 
Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (D22), 48 (D23), 72 (D24), 96 (D25) 
 
Revised table and footnotes: 
 
 
SCR 
CHECK-
IN 
TREATMENT 
CHECK-
OUT 
FOLLOW UP  
 
DAY 
-21 
to -2 
-1 
1 
2-5 
 
6-
16 
17 
18 
19 
20 
21 
22-24 
25  
32 
EARLY 
WITHDRAWAL 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check-in 
questions 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, 
BMIb 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV/ Hepatitis 
B, C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
pregnancy testc 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
FSHc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine 
drug/alcohol 
breathalyzer/ 
urine cotinine 
screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Labs 
hematology, 
chemistry, 
urinalysis)d 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Coagulationd 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Physical exame 
X 
X 
 
X 
 
 
 
 
 
 
X 
X 
 
X 
Heart Murmurf  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Vital signs 
(blood pressure, 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 


 
                                                                            Protocol Clarification Letter, v1.0 
 
 
 
 
TBAJ-876-CL002 
 
 
 
 
       23-June-2022 
 
Page 6 of 21 
 
SCR 
CHECK-
IN 
TREATMENT 
CHECK-
OUT 
FOLLOW UP  
 
DAY 
-21 
to -2 
-1 
1 
2-5 
 
6-
16 
17 
18 
19 
20 
21 
22-24 
25  
32 
EARLY 
WITHDRAWAL 
pulse, 
temperature, 
respiration rate, 
and pulse 
oximetry)g 
Concomitant 
medication 
reviewh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Midazolam 
Dosej 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Digoxin Dosek 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
TBAJ-876l 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
12-lead safety 
ECGsm 
 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Plasma for PKn 
 
 
X 
X 
 
X 
 
 
X 
X 
X 
X 
 
 
SCR=screening; ECG = electrocardiogram; FSH = follicle-stimulating hormone; FU = follow up; HIV = human immunodeficiency virus; N/A = not 
applicable; PK = pharmacokinetic; SCR = screening 
a. 
Confinement to start at check-in (Evening of Day 1) until 24 hours after dosing on Day 25. 
b. Height will be done at screening only and used for BMI calculation at screening and day -1 check in. 
c. 
Serum pregnancy test done at screening, check-in, and Day 25 for females only. FSH completed for postmenopausal females only. 
d. Safety laboratory assessments. The following analyses will be performed at the following timepoints: Screening, Day -1, Day 2, Day 3, Day 7, 
Day 20, Day 21, Day 22, and Day 25. 
 
• 
Hematology: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell (RBC) count, reticulocyte count, and platelet 
count. 
• 
Coagulation Tests: Activated partial thromboplastin time (aPTT2), Prothrombin time (PT2) 
• 
Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK), direct, indirect, and total bilirubin, 
alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium (Na+), potassium (K+), 
chloride (CL-), lactate dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and bicarbonate, lipase, and 
amylase 


 
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TBAJ-876-CL002 
 
 
 
 
       23-June-2022 
 
Page 7 of 21 
• 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN), according to FDA guidance criteria (see Appendix 3), the 
following tests should be performed: creatine phosphokinase of myocardial band (CPK-MB) and cardiac troponin T I.  
• 
Urinalysis: The following will be evaluated by an automated or manual urine “dipstick” method: pH, specific gravity, protein, glucose, 
ketones, bilirubin, creatinine, nitrite, sodium, urobilinogen, blood, myoglobin, leukocyte esterase. If protein, occult blood, nitrate, or 
leukocyte esterase values are out of range, a microscopic examination will be performed.  Myoglobin will be collected but results will 
not be required for dose qualification. 
• 
Urine Drug, Cotinine, and Alcohol Breathalyzer Screens - Urine samples will be tested for drugs of abuse (amphetamines, 
benzodiazepines, barbiturates, cannabinoids, cocaine, opiates) cotinine, and alcohol at screening and check-in only. 
e. 
Physical exam will be performed on Screening, Check-in (Day-1), Day 3, Day 22, and Day 25. 
f. 
Heart murmur: Presence of heart murmur 
g. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be measured at screening, and 
check-in (Day -1). 
Furthermore, vital signs should also be taken once daily on Days 3-5, Days 7 - 19 (6 hours post dose on dosing days and around the 
same time on non-dosing days), Day 22-Day 23 (6 hours after Dosing) and Day 25 (prior to discharge) or early withdrawal (vital signs 
must be done within 15 minutes before review of medication and collection of adverse experiences). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the defined time points in 
flowchart at study hours pre-dose, 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24.  
Orthostatic blood pressure and heart rate should be measured at study hours pre-dose, 2, 6 and 12 time points on Days 1, 2, 6, 20, 21 
and 24, after subjects are in supine position for at least 2 minutes and then again after standing for at least 1 minute), except when 
they are supine or semi-reclined because of study procedures and/or adverse events, or as deemed necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
h. On Day 32, follow-up questioning on concomitant medications and adverse events will be completed by a phone call. 
i. 
Adverse events to be monitored from the time of informed consent signing throughout the study via safety assessments, observation, and 
participant reporting. Specific adverse event questions will be posed daily throughout the study until Day 25 within ± 15 minutes and a follow-
up phone call on Day 32. 
j. 
Midazolam Dose on Day 1 and Day 20 under fasted conditions 
k. Digoxin Dose on Day 2 and Day 21 under fasted conditions 
l. 
TBAJ-876 will be dosed as following: 
a. 200 mgTBAJ-876 on Day 6 - 13 under fed conditions 
b. 165 mg TBAJ-876 on Day 14 – 19 under Fed conditions 
c. 
200 mg TBAJ-876 on Day 20 - 21 under fasted conditions 
d. 150 mg TBAJ-876 on Day 22 - 24 under fed conditions 
m. 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or designee. Single ECGs will be completed at 
screening, Day -1, 2, 3, 7, 20, 21, 22 on Day 25 or upon early withdrawal. Furthermore, ECGs should also be taken on Digoxin dosing 


 
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TBAJ-876-CL002 
 
 
 
 
       23-June-2022 
 
Page 8 of 21 
days, on Day 2 and Day 21, at study hours 0 pre-dose, 0.5, 1, 2, 6, and 12 within 15 minutes of the defined time points. The pre-dose 
ECG should be completed within 90 minutes prior to dosing and all ECGs should be completed prior to blood draws. If a participant 
experiences a post-dosing QTcF >500 ms or a change-from-baseline QTcF >60 ms, after repeat testing, additional ECGs should be recorded 
until normalization or return to baseline 
n. Blood plasma samples will be drawn at the following timepoints: 
• 
Midazolam: Day 1 and Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours 
• 
TBAJ-876: Day 17: pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24 hours 
• 
Digoxin:  
o 
Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 3), 48 (D4), 72 (D5), 96 (D6) hours 
o 
Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (D22), 48 (D23), 72 (D24), 96 (D25) 
 


 
 
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23-June-2022 
 
Page 9 of 21 
2. Updated Inclusion/Exclusion Language (Inclusion Section 5.1 / Exclusion Section 5.2) 
Current Inclusion #8: 
8. If a non-vasectomized male (or male vasectomized less than 6 months prior to study start) he 
must agree to the following during study participation and for 90 days after the last follow-up 
visit (or until at least 90 days after the date of early withdrawal): 
• Use a condom with spermicide while engaging in sexual activity or be sexually 
abstinent; and  
• Not donate sperm during this time.  
In the event the sexual partner is surgically sterile or postmenopausal, use of a condom with 
spermicide is not necessary. None of the birth control restrictions listed above are required for 
vasectomized males whose procedure was performed more than 120 days before study start. 
Revised Inclusion #8: 
8. If a non-vasectomized male (or male vasectomized less than 6 months prior to study start) he 
must agree to the following during study participation and for 90 days after the last follow-up 
visit (or until at least 90 days after the date of early withdrawal): 
• Use a condom with spermicide while engaging in sexual activity or be sexually 
abstinent; and  
• Not donate sperm during this time.  
In the event the sexual partner is surgically sterile or postmenopausal, use of a condom with 
spermicide is not necessary. None of the birth control restrictions listed above are required for 
vasectomized males whose procedure was performed more than 120 days 6 months before study 
start. 
Current Exclusion #12: 
12.  
Seated or supine blood pressure is less than 90/40 mmHg or greater than 150/90 mmHg at 
screening, Day -1 (check-in), or pre-dose. Out of range vital signs may be repeated twice for 
confirmation. Out of range values will not be considered AEs if the repeat assessment is in range. 
Revised Exclusion #12: 
12.  
Seated or supine blood pressure is less than 90/40 mmHg or greater than 150/90 mmHg at 
screening, Day -1 (check-in), or pre-dose Day 1. Out of range vital signs may be repeated twice for 
confirmation. Out of range values will not be considered AEs if the repeat assessment is in range. 
Current Exclusion #13: 
13.  
Heart rate is lower than 60 beats per minute (bpm) or higher than 100 bpm at screening, Day 
-1 (check-in), or pre-dose. Out of range vital signs may be repeated once for confirmation. Out of 
range values will not be considered AEs if the repeat assessment is in range.  
 


 
 
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23-June-2022 
 
Page 10 of 21 
Revised Exclusion #13: 
13. 
 Heart rate is lower than 60 beats per minute (bpm) or higher than 100 bpm at screening, Day 
-1 (check-in), or pre-dose Day 1. Out of range vital signs may be repeated once for confirmation. Out 
of range values will not be considered AEs if the repeat assessment is in range. 
Current Exclusion #15: 
15. 
QTcF interval >450 ms for males or >470 ms for females at screening, Day -1, or Day 2 (pre-
dose), or history of prolonged QT syndrome. PR interval < 200 ms at screening, Day -1, or Day 2 
pre-dose. Out of range values may be repeated twice for confirmation. The average QTcF and PR 
intervals of the three ECG recordings will be used to determine qualification.  
Revised Exclusion #15: 
15. 
QTcF interval >450 ms for males or >470 ms for females at screening, Day -1, or Day 2 (pre-
dose), or history of prolonged QT syndrome. PR interval < 200 ms at screening, Day -1, or Day 2 
pre-dose. Out of range values may be repeated twice for confirmation. The average QTcF andor PR 
intervals of the three ECG recordings will be used to determine qualification. 
3. Restrictions Section 5.3 
Current Wording: 
Subjects must not donate blood from 56 days or plasma from 7 days prior to the first dose of study 
medication until the last follow-up visit (Day 32 phone call) or early withdrawal visit is completed. 
It is recommended that blood/plasma donations not be made for at least 30 days after the last follow-
up visit or early withdrawal visit. 
Subjects must not use tobacco- or nicotine-containing products (including smoking cessation 
products) from 6 months prior to the first dose of study medication until the last follow-up visit or 
early withdrawal visit is completed. 
Subjects must not consume alcohol from 72 hours prior to the first dose of study medication until the 
last follow-up visit or early withdrawal visit is completed. However, allowance for an isolated single 
incidental consumption may be evaluated and approved by the study Investigator based on the 
potential for interaction with the study drug. 
Subjects must not consume beverages or foods that contain grapefruit or Mandarin oranges from 10 
days before the first dose of study medication, or poppy seeds, broccoli, Brussels sprouts, 
pomegranate, star fruit, cherries, char-grilled meat, or caffeine/xanthine from 24 hours before the first 
dose of study medication, until the last follow-up visit, or early withdrawal visit is completed. 
Subjects will be instructed not to consume any of the above products; however, allowance for an 
isolated single incidental consumption may be evaluated and approved by the study Investigator 
based on the potential for interaction with the study drug. 
Subjects must not engage in strenuous exercise from 48 hours prior to the first dose of study 
medication until after discharge from the clinic. For follow-up visits, subjects must not engage in 
strenuous exercise during the 3 days prior to the visit. Any report of exercise will be documented and 
recoded as a protocol deviation. Subjects may continue in the study at the discretion of the study 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 11 of 21 
Investigator. 
Revised Wording: 
Subjects must not donate blood from 56 days or plasma from 7 days prior to the first dose of study 
medication until the last follow-up visit (Day 32 phone call) or early withdrawal visit is completed. 
It is recommended that blood/plasma donations not be made for at least 30 days after the last follow-
up visit or early withdrawal visit. 
Subjects must not use tobacco- or nicotine-containing products (including smoking cessation 
products) from 6 months prior to the first dose of study medication until the last follow-up visit or 
early withdrawal visit is completed. 
Subjects must not consume alcohol from 72 hours prior to the first dose of study medication until the 
last follow-up visit or early withdrawal visit is completed. However, allowance for an isolated single 
incidental consumption may be evaluated and approved by the study Investigator based on the 
potential for interaction with the study drug. 
Subjects must not consume beverages or foods that contain grapefruit or Mandarin oranges from 10 
days before the first dose of study medication, or poppy seeds, broccoli, Brussels sprouts, 
pomegranate, star fruit, cherries, char grilled meat, or caffeine/xanthine from 24 hours before the first 
dose of study medication, until Day 25 the last follow up visit, or early withdrawal visit is completed. 
Subjects will be instructed not to consume any of the above products; however, allowance for an 
isolated single incidental consumption may be evaluated and approved by the study Investigator 
based on the potential for interaction with the study drug. 
Subjects must not engage in strenuous exercise from 48 hours prior to the first dose of study 
medication until Day 32 follow up call. after discharge from the clinic. For follow up visits, 
subjects must not engage in strenuous exercise during the 3 days prior to the visit. Any report 
of exercise will be documented and recoded as a protocol deviation. Subjects may continue in the 
study at the discretion of the study Investigator. 
4. Check-in Procedures, Section 7.2 
Current Wording: 
Subjects will check into the clinic on Day -1. 
At check-in, all subjects will be evaluated to confirm they continue to meet all the inclusion criteria 
(Section 5.1) and none of the exclusion criteria (Section 5.2).  
Subjects will undergo the following assessments during the confinement period prior to dosing: 
• 
Physical examinations 
• 
Weight 
• 
Vital signs (blood pressure, pulse rate, respiration rate, temperature, and pulse oximetry) 
• 
12-lead ECG 
• 
Clinical laboratory tests (hematology, coagulation, chemistry, and urinalysis) – myoglobin 
will be collected but results will not be required for dose qualification. 
• 
Urine drug, alcohol, and cotinine screens – results must be negative for the subject to continue 
study participation 


 
 
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23-June-2022 
 
Page 12 of 21 
• 
Serum pregnancy test (all female subjects) – results must be negative for the subject to 
continue study participation 
• 
Concomitant medication review 
Revised Wording: 
Subjects will check into the clinic on Day -1. 
At check-in, all subjects will be evaluated to confirm they continue to meet all the inclusion criteria 
(Section 5.1) and none of the exclusion criteria (Section 5.2).  
Subjects will undergo the following assessments during the confinement period prior to dosing: 
• 
Physical examinations 
• 
Weight and BMI (height from screening will be used to calculate the BMI) 
• 
Vital signs (blood pressure, pulse rate, respiration rate, temperature, and pulse oximetry) 
• 
12-lead ECG 
• 
Clinical laboratory tests (hematology, coagulation, chemistry, and urinalysis) – myoglobin 
will be collected but results will not be required for dose qualification. 
• 
Urine drug, alcohol breathalyzer, and urine cotinine screens – results must be negative for 
the subject to continue study participation 
• 
Serum pregnancy test (all female subjects) – results must be negative for the subject to 
continue study participation 
• 
Concomitant medication review 
5. Laboratory parameters, Section 7.6.2 
Current Wording: 
Clinical laboratory evaluations will be performed at the times noted on the appropriate schedule of 
events (Section 1.2). A Clinical Laboratory Improvement Amendments (CLIA) certified laboratory 
will perform all clinical laboratory tests for this study. 
• Hematology: hemoglobin, hematocrit, , red blood cell (RBC) count, white blood cell count 
with differential, reticulocyte count, and platelet count. 
• Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase 
(CPK), direct, indirect, and total bilirubin, alkaline phosphatase (ALP), aspartate transaminase 
(AST), alanine transaminase (ALT), sodium (Na+), potassium (K+), chloride (Cl-), lactate 
dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and 
bicarbonate, lipase, and amylase. 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN) the following tests 
should be performed: creatine phosphokinase of myocardial band (CPK-MB), trypsin like 
immunoreactivity, and cardiac troponin I. 
• Serology: hepatitis B surface antigen, hepatitis C antibody, and HIV 
• Coagulation: prothrombin time (PT2) and activated partial thromboplastin time (aPTT2). 
• Urinalysis - The following will be evaluated by an automated or manual urine “dipstick” 
method: pH, specific gravity, protein, glucose, ketones, bilirubin, creatinine, nitrite, sodium, 
urobilinogen, myoglobin, blood, leukocyte esterase, and urobilinogen. If protein, occult 
blood, nitrite, or leukocyte esterase values are out of range, a microscopic examination will 


 
 
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23-June-2022 
 
Page 13 of 21 
be performed. Myoglobin will be collected but results will not be required for dose 
qualification. 
• Urine Drug, Cotinine, and Alcohol Screens - Urine samples will be tested for drugs of abuse 
(amphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, opiates) cotinine, and 
alcohol. 
• Pregnancy test (all female subjects). 
• FSH (female subjects claiming post-menopausal status). 
Revised Wording: 
Clinical laboratory evaluations will be performed at the times noted on the appropriate schedule of 
events (Section 1.2). A Clinical Laboratory Improvement Amendments (CLIA) certified laboratory 
will perform all clinical laboratory tests for this study. 
• Hematology: hemoglobin, hematocrit, , red blood cell (RBC) count, white blood cell count 
with differential, reticulocyte count, and platelet count. 
• Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase 
(CPK), direct, indirect, and total bilirubin, alkaline phosphatase (ALP), aspartate transaminase 
(AST), alanine transaminase (ALT), sodium (Na+), potassium (K+), chloride (Cl-), lactate 
dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and 
bicarbonate, lipase, and amylase. 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN) the following tests 
should be performed: creatine phosphokinase of myocardial band (CPK-MB), trypsin like 
immunoreactivity, and cardiac troponin T. 
• Serology: hepatitis B surface antigen, hepatitis C antibody, and HIV 
• Coagulation: prothrombin time (PT2) and activated partial thromboplastin time (aPTT2). 
• Urinalysis - The following will be evaluated by an automated or manual urine “dipstick” 
method: pH, specific gravity, protein, glucose, ketones, bilirubin, creatinine, nitrite, sodium, 
urobilinogen, myoglobin, blood, leukocyte esterase, and urobilinogen. If protein, occult 
blood, nitrite, or leukocyte esterase values are out of range, a microscopic examination will 
be performed. Myoglobin will be collected but results will not be required for dose 
qualification. 
• Urine Drug, Urine Cotinine, and Alcohol Breathalyzer Screens - Urine samples will be 
tested for drugs of abuse (amphetamines, benzodiazepines, barbiturates, cannabinoids, 
cocaine, opiates) cotinine, and alcohol at screening and check-in only. 
• Pregnancy test (all female subjects). 
• FSH (female subjects claiming post-menopausal status). 
 
 


 
 
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Page 14 of 21 
6. Vital Signs, Section 7.6.3 
Current Wording: 
Vital signs (blood pressure, heart rate [pulse], temperature, respiration rate, and pulse oximetry) 
should be measured at screening, check-in, and Day -1. Vital sign measurements should be taken 
within 90 minutes prior to dosing and within 15 minutes of the defined time points in flowchart at 
study hours 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24. Furthermore, vital signs should 
also be taken once daily on Day 7 through Day 20 (6 hours after Dosing) and Day 25 or early 
withdrawal (must be done within 15 minutes before review of medication and collection of adverse 
experiences)Both blood pressure and heart rate should be captured simultaneously. Blood pressure 
and heart rate should be measured after subjects are in supine position for at least 2 minutes and then 
again after standing for at least 1 minute (starting with 2 hours post dose), except when they are 
supine or semi-reclined because of study procedures and/or adverse events, or as deemed necessary 
by the Investigator. 
Revised Wording: 
Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse 
oximetry) should be measured at screening, and check-in, Day -1.  
Furthermore, vital signs should also be taken once daily on Day 3-5, 7 through Day 19 (6 
hours post dose on dosing days and around the same time on non-dosing days), Day 22-Day 23 
(6 hours after Dosing) and Day 25 (prior to discharge) or early withdrawal (vital signs must 
be done within 15 minutes before review of medication and collection of adverse experiences). 
Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 
minutes of the defined time points in flowchart at study hours pre-dose, 0.5, 1, 2, 6, and 12 on 
Days 1, 2, 6, 20, 21, and 24.  
Orthostatic blood pressure and heart rate should be measured at study hours Pre-dose, 2, 6 
and 12 time points on Days 1, 2, 6, 20, 21 and 24, after subjects are in supine position for at 
least 2 minutes and then again after standing for at least 1 minute), except when they are 
supine or semi-reclined because of study procedures and/or adverse events, or as deemed 
necessary by the Investigator. 
Both blood pressure and heart rate should be captured simultaneously. 
7. Physical Examination, Section 7.6.4 
Current Wording: 
Physical examinations including height and weight measurements and presence of heart murmur, will 
be conducted in the times noted on the appropriate events schedule (Section 1.2). 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 15 of 21 
Revised Wording: 
Physical examinations including height and weight measurements and presence of heart murmur, 
will be conducted in the timesdays noted on the appropriate events schedule (Section 1.2). 
8. Electrocardiograms, Section 7.6.5 
Current Wording: 
Group 1 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 3, 7, 20, 21, 22 and on Day 25 or 
upon early withdrawal. The pre-dose ECG should be completed within 20 minutes prior to the pre-
dose blood draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline 
QTcF >60 ms, after repeat testing, additional ECGs should be recorded until normalization or return 
to baseline. 
Revised Wording: 
Group 1 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 3, 7, 20, 21, 22 and on Day 25 or 
upon early withdrawal. Furthermore, ECGs should also be taken on Digoxin dosing days, on Day 
2 and Day 21, at study hours 0,predose, 0.5, 1, 2, 6, and 12 within 15 minutes of the defined time 
points. The pre-dose ECG should be completed within 20 minutes prior to the pre-dose blood draw. 
If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline QTcF >60 ms, 
after repeat testing, additional ECGs should be recorded until normalization or return to baseline. 
9. Appendix 1 , PK Processing Instructions Table and Plasma from whole blood 
Midazolam, Digoxin and TLD samples Processing Instructions Table 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 16 of 21 
Current Table for PK Processing Instructions: 
Processing Instructions 
1 
Samples will be collected via direct venipuncture at the time points delineated in the 
appropriate Events Schedule (Section 1.2).  
2 
Blood will be drawn into pre-chilled 4 mL evacuated tubes containing K3-EDTA and 
immediately placed on wet ice and then processed to plasma within 60 minutes. 
3 
Samples will be centrifuged at 1500 g at approximately 4°C (± 10 degrees) for 
10 minutes. After centrifugation, two aliquots of plasma (the first containing at least 
0.5 mL and the second containing the remainder of the plasma) will be removed and 
placed in appropriately labeled 1 mL polypropylene vials. 
4 
The aliquots will be immediately placed on dry ice. Within 90 minutes of collection, 
the aliquots will be stored in a freezer set at -80°C ± 10°C and remain in the freezer 
until transferred for analysis. 
5 
Samples will be transferred at the agreed upon intervals. 
6 
The aliquots will be transferred on dry ice to the Alliance Pharma, Inc. bioanalytical 
laboratory for the determination of plasma concentrations of TBAJ-876 and its 
metabolites (M2 and M3) using a validated procedure at Alliance Pharma. 
7 
Blood sampling, plasma processing, and storage time will be documented in the study 
records. 
 
Revised Table for PK Processing Instructions: 
Processing Instructions 
1 
Samples will be collected via direct venipuncture or peripheral venous catheter at 
the time points delineated in the appropriate Events Schedule (Section 1.2).  
2 
Blood will be drawn into pre-chilled 4 mL evacuated tubes containing K3-EDTA and 
immediately placed on wet ice and then processed to plasma within 60 minutes. 
3 
Samples will be centrifuged at 1500 g at approximately 4°C (± 10 degrees) for 
10 minutes. After centrifugation, two aliquots of plasma (the first containing at least 
0.5 mL and the second containing the remainder of the plasma) will be removed and 
placed in appropriately labeled 1 mL polypropylene vials. 
4 
The aliquots will be immediately placed on dry ice. Within 90 minutes of collection, 
the aliquots will be stored in a freezer set at -80°C ± 10°C and remain in the freezer 
until transferred for analysis. 
5 
Samples will be transferred at the agreed upon intervals. 
6 
The aliquots will be transferred on dry ice to the Alliance Pharma, Inc. bioanalytical 
laboratory for the determination of plasma concentrations of TBAJ-876 and its 
metabolites (M2 and M3) using a validated procedure at Alliance Pharma. 
7 
Blood sampling, plasma processing, and storage time will be documented in the study 
records. 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 17 of 21 
Current Table for Processing Instructions of Plasma from whole blood Midazolam, Digoxin and 
TLD samples: 
Processing Instructions 
1 
Samples will be collected via direct venipuncture at the time points delineated in the 
appropriate Events Schedule (Section 13).  
2 
Blood will be drawn into pre-chilled evacuated tubes containing K2-EDTA and 
immediately placed on wet ice and then processed to plasma within 60 minutes. 
3 
Samples will be centrifuged at 1500 g at approximately 4°C (± 10 degrees) for 
10 minutes. After centrifugation, two aliquots of plasma will be removed and placed 
in appropriately labelled polypropylene vials. 
4 
The aliquots will be immediately placed on dry ice. Within 90 minutes of collection, 
the aliquots will be stored in a freezer set at -80°C ± 10°C and remain in the freezer 
until transferred for analysis. 
5 
Samples will be transferred at the agreed upon intervals. 
6 
The aliquots will be transferred on dry ice to the Pyxant bioanalytical laboratory for 
the determination of plasma concentrations of Midazolam and Digoxin using a 
validated procedure. 
7 
Blood sampling, plasma processing, and storage time will be documented in the study 
records. 
 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 18 of 21 
Revised Table for Processing Instructions of Plasma from whole blood Midazolam, Digoxin and 
TLD samples: 
Processing Instructions 
1 
Samples will be collected via direct venipuncture or peripheral venous catheter at 
the time points delineated in the appropriate Events Schedule (Section 13).  
2 
Blood will be drawn into pre-chilled evacuated tubes containing K2-EDTA and 
immediately placed on wet ice and then processed to plasma within 60 minutes. 
3 
Samples will be centrifuged at 1500 g at approximately 4°C (± 10 degrees) for 
10 minutes. After centrifugation, two aliquots of plasma will be removed and placed 
in appropriately labelled polypropylene vials. 
4 
The aliquots will be immediately placed on dry ice. Within 90 minutes of collection, 
the aliquots will be stored in a freezer set at -80°C ± 10°C and remain in the freezer 
until transferred for analysis. 
5 
Samples will be transferred at the agreed upon intervals. 
6 
The aliquots will be transferred on dry ice to the Pyxant bioanalytical laboratory for 
the determination of plasma concentrations of Midazolam and Digoxin using a 
validated procedure. 
7 
Blood sampling, plasma processing, and storage time will be documented in the study 
records. 
 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 19 of 21 
10. Appendix 3, Cardiovascular Table 
Current table: 
CARDIOVASCULAR 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cardiac Rhythm 
 
asymptomatic, 
transient signs, no 
Rx required 
recurrent/persistent; 
symptomatic Rx 
required 
unstable 
dysrythmia; 
hospitalization and 
treatment required 
Hypertension 
transient increase 
> 20 mm/Hg; no 
treatment1 
recurrent, chronic 
increase > 
20mm/Hg. 
/treatment required 
acute treatment 
required; outpatient 
treatment or 
hospitalization 
possible 
end organ damage 
or hospitalization 
required 
Hypotension 
transient 
orthostatic 
hypotension with 
heart rate 
increased by <20 
beat/min or 
decreased by <10 
mm Hg systolic 
BP, No treatment 
required1 
symptoms due to 
orthostatic 
hypotension or BP 
decreased by <20 
mm Hg systolic; 
correctable with oral 
fluid treatment 
requires IV fluids; no 
hospitalization 
required 
mean arterial 
pressure <60mm/ 
Hg or end organ 
damage or shock;   
requires 
hospitalization and 
vasopressor 
treatment 
Pericarditis 
minimal effusion 
mild/moderate 
asymptomatic 
effusion, no 
treatment 
symptomatic 
effusion; pain; EKG 
changes 
tamponade; 
pericardiocentesis 
or surgery required 
Hemorrhage, Blood 
Loss 
microscopic/occult 
mild, no transfusion 
gross blood loss; 1-2 
units transfused 
massive blood 
loss; > 3 units 
transfused 
 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 20 of 21 
Revised table – added footnotes: 
CARDIOVASCULAR 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cardiac Rhythm 
 
asymptomatic, 
transient signs, no 
Rx required 
recurrent/persistent; 
symptomatic Rx 
required 
unstable 
dysrythmia; 
hospitalization and 
treatment required 
Hypertension 
transient increase 
> 20 mm/Hg; no 
treatment1 
recurrent, chronic 
increase > 
20mm/Hg. 
/treatment required 
acute treatment 
required; outpatient 
treatment or 
hospitalization 
possible 
end organ damage 
or hospitalization 
required 
Hypotension 
transient 
orthostatic 
hypotension with 
heart rate 
increased by <20 
beat/min or 
decreased by <10 
mm Hg systolic 
BP, No treatment 
required1 
symptoms due to 
orthostatic 
hypotension or BP 
decreased by <20 
mm Hg systolic; 
correctable with oral 
fluid treatment2 
requires IV fluids; no 
hospitalization 
required 
mean arterial 
pressure <60mm/ 
Hg or end organ 
damage or shock;   
requires 
hospitalization and 
vasopressor 
treatment 
Pericarditis 
minimal effusion 
mild/moderate 
asymptomatic 
effusion, no 
treatment 
symptomatic 
effusion; pain; EKG 
changes 
tamponade; 
pericardiocentesis 
or surgery required 
Hemorrhage, Blood 
Loss 
microscopic/occult 
mild, no transfusion 
gross blood loss; 1-2 
units transfused 
massive blood 
loss; > 3 units 
transfused 
1 In this healthy volunteer study, asymptomatic transient orthostatic hypotension will be defined as heart rate 
increased by 20 ≥ beats/min or systolic BP decreased by ≥10 mm Hg.  This will be captured as a Grade 1 Adverse 
Event. 
2 In this healthy volunteer study, Grade 2 orthostatic hypotension will be defined as symptoms due to systolic BP 
decreased by ≥20 mm Hg; correctable with oral fluid treatment.  This will be captured as a Grade 2 Adverse Event. 
11. Appendix 3, A. Tables for Laboratory Abnormalities 
Current Language above the table: 
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
 
 


 
 
Protocol Clarification Letter, v1.0 
 
 
TBAJ-876-CL002 
 
 
23-June-2022 
 
Page 21 of 21 
Revised Language above the table: 
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. In all cases PI should consult the DMID (toxicity) table 
(Appendix 3) when assessing laboratory abnormalities. 


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CONFIDENTIAL 
Protocol Number: 
TBAJ-876-CL002 
Title: 
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, 
Tolerability, and the Induction potential of TBAJ-876 on CYP3A4 
and P-glycoprotein and the Inhibition potential of TBAJ-876 on P-
glycoprotein in Healthy Adult Subjects 
Drug(s)/Combination(s): 
TBAJ-876 
Protocol Version/Date: 
 VERSION 1.0 / 20May2022 (Final) 
Protocol Name: 
 TBAJ-876-CL002 






TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 4 of 84 
 
Table of Contents 
PROTOCOL SIGNATURE PAGE ....................................................................................... 2 
PRINCIPAL INVESTIGATOR PROTOCOL SIGNATURE PAGE ........................................ 3 
1 
Synopsis ............................................................................................................................11 
1.1 
Synopsis Summary ..................................................................................................11 
1.2 
Flow Chart ...............................................................................................................17 
 
Schedule of Assessments & Procedures, Group 1: Midazolam, 
Digoxin ......................................................................................................17 
 
Schedule of Assessments & Procedures Group 2: Dolutegravir, 
Tenofovir disoproxil fumarate, Lamivudine ................................................20 
2 
Introduction ........................................................................................................................23 
2.1 
Background .............................................................................................................23 
2.2 
Tuberculosis and Rationale for New Medication ......................................................23 
2.3 
Preclinical Studies ...................................................................................................23 
 
Primary pharmacology ..............................................................................23 
 
Safety Assessment ...................................................................................24 
2.3.2.1 
Toxicology ............................................................................................................... 24 
2.3.2.2 
Safety Pharmacology .............................................................................................. 26 
2.3.2.3 
Potential adverse effects in human subjects .......................................................... 28 
 
Pharmacokinetics and Product Metabolism in Animals..............................28 
2.4 
Clinical Findings ......................................................................................................31 
 
Safety ........................................................................................................31 
 
Pharmacokinetics ......................................................................................32 
2.5 
Rationale for Drug-Drug Interaction Studies.............................................................33 
2.6 
Rationale for the TBAJ-876 Dose Regimen .............................................................35 
3 
Study Objectives ................................................................................................................35 
3.1 
Primary Objectives ...................................................................................................35 
3.2 
Secondary Objectives ..............................................................................................36 
4 
Study Design .....................................................................................................................36 
4.1 
Summary of Study Design .......................................................................................36 
4.2 
Treatment Plan; Schedule of Assessments..............................................................37 
5 
Study Population ................................................................................................................39 
5.1 
Inclusion Criteria ......................................................................................................39 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 5 of 84 
 
5.2 
Exclusion Criteria .....................................................................................................41 
5.3 
Restrictions ..............................................................................................................42 
5.4 
Stopping Rules ........................................................................................................43 
5.5 
Discontinuation from Treatment/Study .....................................................................43 
5.6 
Trial Duration ...........................................................................................................44 
6 
Treatment ..........................................................................................................................44 
6.1 
Administration of TBAJ-876 Oral Suspension ..........................................................44 
6.2 
Administration of the Interaction Products ................................................................44 
6.3 
Fasting/Meals/Beverages ........................................................................................45 
6.4 
Subject Compliance .................................................................................................45 
6.5 
Method of Treatment Assignment ............................................................................45 
6.6 
Handling, Storage and Accountability ......................................................................46 
7 
Study Procedures ..............................................................................................................46 
7.1 
Screening ................................................................................................................46 
7.2 
Check-in Procedures ...............................................................................................47 
7.3 
Subject Assignment .................................................................................................47 
7.4 
Confinement ............................................................................................................47 
7.5 
Blood Sampling, Processing and Shipment .............................................................47 
 
Group 1 .....................................................................................................48 
 
Group 2 .....................................................................................................49 
 
Pharmacokinetic Sampling Time Windows ................................................50 
7.6 
Safety Monitoring and Procedures ...........................................................................51 
 
Adverse Events .........................................................................................51 
 
Laboratory parameters ..............................................................................51 
 
Vital Signs .................................................................................................52 
 
Physical Examination ................................................................................52 
 
Electrocardiograms ...................................................................................52 
 
Other Safety Measures .............................................................................53 
8 
Adverse Events ..................................................................................................................53 
8.1 
Definitions ................................................................................................................53 
 
Adverse Event ...........................................................................................53 
 
Serious Adverse Event ..............................................................................53 
 
Attribution/Causality ..................................................................................54 
8.2 
Reporting .................................................................................................................56 


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Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
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CONFIDENTIAL 
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Adverse Event ...........................................................................................56 
8.3 
Serious Adverse Event Reporting ............................................................................57 
8.4 
Follow-up of Adverse Events ...................................................................................58 
8.5 
Post-Trial Serious Adverse Events ..........................................................................58 
8.6 
Clinical Laboratory Adverse Events .........................................................................58 
8.7 
Drug Interaction .......................................................................................................59 
8.8 
Pregnancy ...............................................................................................................59 
8.9 
Monitoring and Safety for Specific Toxicities ............................................................59 
9 
General Principles ..............................................................................................................60 
9.1 
Basic Principles .......................................................................................................60 
9.2 
Institutional Review Board .......................................................................................60 
9.3 
Informed Consent ....................................................................................................60 
9.4 
Indications for Subject Withdrawal ...........................................................................60 
9.5 
Termination of Study ................................................................................................61 
9.6 
Documentation ........................................................................................................61 
9.7 
Trial Monitoring ........................................................................................................61 
9.8 
Reimbursement, Indemnity, and Insurance ..............................................................61 
10 Statistical Analysis .............................................................................................................61 
10.1 Analysis Population .................................................................................................62 
10.2 Sample Size ............................................................................................................62 
10.3 Interim analysis ........................................................................................................64 
10.4 Demographics and Other Baseline Characteristics Analysis ....................................64 
10.5 Safety and Tolerability Analysis ...............................................................................64 
10.6 Pharmacokinetic analysis ........................................................................................65 
11 Facilities .............................................................................................................................66 
12 Drug Supplies ....................................................................................................................67 
13 Administrative Issues .........................................................................................................68 
14 References ........................................................................................................................68 
APPENDIX 1 
PHARMACOKINETIC SAMPLE COLLECTION, PROCESSING, 
AND SHIPMENT INSTRUCTIONS ...........................................................................................70 
APPENDIX 2 DESCRIPTION AND COMPOSITION OF TEST PRODUCT ...............................73 
APPENDIX 3 DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASE TOXICITY 
TABLE ......................................................................................................................................75 
 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 7 of 84 
 
LIST OF TABLES 
Table 1 
Plasma Exposure to TBAJ-876 and Metabolites in Toxicity and Safety Pharmacology 
Studies ....................................................................................................................27 
Table 2 
Plasma Exposure to TBAJ-876 and Metabolites vs. BDQ and BDQ-M2 Following 4-
week Repeated Oral Administration to Mice ............................................................30 
Table 3 
Mean Cmax and AUC0-24 of TBAJ-876 and M3 in the MAD study. ..............................33 
Table 4 
Investigational Medicinal Product (IMP) Details .......................................................38 
Table 5 
Total predicted Volume of Blood to be Collected for Testing: Group 1 .....................49 
Table 6 
Total predicted Volume of Blood to be Collected for Testing: Group 2 .....................50 
Table 7 
Acceptable Pharmacokinetic Sampling Time Windows ............................................51 
Table 8 
Adverse Event Attribution/Causality Ratings ............................................................55 
Table 9 
Definitions for Adverse Event Severity Gradings ......................................................56 
Table 10 Standard Deviations and Sample Sizes ...................................................................64 
Table 11 Pharmacokinetic Parameters ...................................................................................66 
 
LIST OF ABBREVIATIONS 
AE 
adverse event  
ALP  
alkaline phosphatase  
ALT  
alanine aminotransferase   
ANOVA  
analysis of variance   
aPTT2  
activated partial prothrombin time   
AST  
aspartate aminotransaminase   
AUC  
area under the (plasma concentration vs. time) curve   
AUCExtrap (%)  
the percentage of AUCinf based on extrapolation   
AUClast  
area under the curve from time 0 hours to last quantifiable concentration   
AUCinf  
area under the curve from time 0 hours to infinity   
AUCtau 
BDQ  
area under the concentration-time curve at the end of a dosing interval  
bedaquiline  
BMI  
body mass index   
BP  
blood pressure   
BUN  
blood urea nitrogen   
bpm  
beats per minute   
Ca  
calcium   
Cavg  
average steady-state plasma concentration   
CL/F  
apparent total clearance after oral administration   
CFR  
Code of Federal Regulations   
CI 
confidence interval   
Cl-  
chloride   


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Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
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Clast  
the last quantifiable concentration determined directly from individual 
concentration-time data 
CLIA  
Clinical Laboratory Improvement Amendments   
Cmax  
maximum concentration   
Cmin  
minimum concentration   
CNS  
central nervous system   
CPK  
creatine phosphokinase   
CPK-MB  
creatine phosphokinase myocardial band  
CRF  
case report form   
cTnT 
cardiac troponin T 
Ctrough  
trough plasma concentration   
CV 
Cardiovascular 
CYP 
DARQ  
cytochrome P450 
diarylquinoline   
DIC 
disseminated intravascular coagulation 
dL  
decilitre   
DMID 
Division of Microbiology and Infectious Diseases 
DTG 
dolutegravir 
ECG 
electrocardiogram  
FDA  
Food and Drug Administration   
FE 
FIH 
food-effect 
first-in-human 
FOB 
Functional observational battery 
FSH 
follicle-stimulating hormone   
g  
gram(s)   
GCP  
Good Clinical Practice   
GLP  
Good Laboratory Practice   
GMR 
Geometric mean ratio 
HBsAg 
Hepatitis B Surface Antigen 
HED  
human equivalent dose   
HIPAA  
Health Insurance Portability and Accountability Act   
HIV  
human immunodeficiency virus   
HCl  
hydrochloride   
HCV 
Hepatitis C Virus 
HR 
Heart rate 
IB  
Investigator Brochure   
ICD  
informed consent document  
ICH  
IMP 
International Conference on Harmonization   
Investigational Medicinal Product 
IND  
Investigational New Drug   
INR  
international normalized ratio   
IP  
Investigational Product   
IRB 
Institutional Review Board 
ISF  
Investigator Site File   
IV 
intravenous 
kg  
kilogram(s)   
K2-EDTA  
ethylenediaminetetraacetic acid   


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
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K+  
potassium  
L  
litre(s)   
LDH  
lactate dehydrogenase  
LDPE 
Low density polyethylene  
LOAEL 
lowest observed adverse effect level 
LOQ  
limit of quantitation   
m  
meter(s)   
MAD  
multiple ascending dose  
MAOI  
monoamine oxidase inhibitor   
max.  
maximum   
mcg  
micrograms 
MDD  
MDR 
major depressive disorder  
multi drug resistant  
MedDRA 
Medical Dictionary for Regulatory Activities 
mg  
milligram(s)   
min.  
minute(s)   
mIU  
milli international units   
mL  
millilitre(s)   
mmHg  
millimetre of mercury  
ms  
millisecond   
MTB / M.tb  
Mycobacterium tuberculosis   
MTD 
maximum tolerated dose 
n or N  
number of occurrences  
NA 
Not assessed 
N/A 
Not applicable 
Na+  
sodium   
NC 
Not calculated 
ND 
Not determined 
ng  
nanogram(s)   
NOAEL  
no observed adverse effect level   
NS 
Nervous System 
OATP  
organic anion transport protein   
OTC 
PaL  
over the counter 
pretomanid + linezolid   
PCR 
Polymerase chain reaction 
P-gp  
P-glycoprotein   
PK 
pharmacokinetic 
PP 
polypropylene 
PRBC 
packed red blood cells 
PT  
prothrombin time   
PTT  
partial thromboplastin time   
QTcF  
QTc interval corrected with Fridericia formula   
RAUC  
accumulation ratio for AUC   
RCmax  
accumulation ratio for Cmax   
rbc  
red blood cell   
Resp 
Respiratory 
rpm  
revolutions per minute   
SAD  
single ascending dose   
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SCR 
screening 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 10 of 84 
 
SAE  
serious adverse event   
SAP  
statistical analysis plan   
SAUC 
sum of the AUC0-24 values of parent drug and its M3 metabolite  
SOC 
System organ class 
SOP 
standard operating procedure 
SP 
Safety Pharmacology Study 
SRC 
Safety Review Committee 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis  
TDF 
tenofovir disoproxil fumarate 
TFV 
tenofovir 
TK 
toxicokinetic 
TLD 
A fixed-dose combination of tenofovir disoproxil fumarate (TDF), 
lamivudine (3TC), and dolutegravir (DTG) 
T½ or t½  
terminal elimination half-life  
Tlag  
time prior to the first measurable (non-zero) concentration   
Tlast 
time of the last quantifiable concentration   
Tmax  
time of the maximum concentration   
ULN 
Upper limit of normal 
Vz/F  
apparent volume of distribution   
WHO  
World Health Organization   
β-hCG  
beta-human chorionic gonadotropin  
λz   
observed terminal elimination rate constant (Lambda-z)  
°C  
degrees Celsius/Centigrade  
3TC 
lamivudine 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 11 of 84 
 
1 
Synopsis 
1.1 Synopsis Summary 
Name of 
Sponsor/Company 
Global Alliance for TB Drug Development 
Name of Finished 
Products: 
TBAJ-876 
Protocol 
Number/Title: 
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, 
Tolerability, and the Induction potential of TBAJ-876 on CYP3A4 and 
P-glycoprotein and the Inhibition potential of TBAJ-876 on P-
glycoprotein in Healthy Adult Subjects 
Treatment 
Indication: 
Tuberculosis 
Study Objectives: 
The primary objective of the study is:    
• 
To evaluate the induction potential of TBAJ-876 on CYP3A4 
and P-glycoprotein (P-gp) and the inhibition potential of TBAJ-
876 on P-gp in healthy adult subjects. 
 
The secondary objectives of the study are:   
• 
To evaluate the effects of multiple-dose administrations of 
TBAJ-876 on the safety and tolerability of midazolam and 
digoxin. 
• 
To evaluate the effects of multiple-dose administration of 
TBAJ-876 on the safety and tolerability of Dolutegravir 
administered as a fixed dose formulation with Tenofovir and 
Lamivudine.(If Group 2 is conducted). 
Study Design 
Overview 
This is a two-part (Group 1 and Group 2) open label drug-drug 
interaction study to be conducted in one study center in the 
United States. 
 
Group 1:  
Will assess the induction potential of TBAJ-876 on the sensitive 
CYP3A4 substrate Midazolam and the inhibition and induction 
potential of TBAJ-876 on the sensitive P-glycoprotein substrate 
Digoxin. 
 
Group 2: 
To be conducted only if the results of Group 1 show that TBAJ-
876 is a moderate inducer of either CYP3A4 (geometric mean 
ratio [GMR] of midazolam area under the curve [AUC] <0.50 
when co-administered with TBAJ-876 versus alone) or P-
glycoprotein (GMR of digoxin AUC <0.50 when co-administered 
with TBAJ-876 versus alone) or a moderate inhibitor of P-
glycoprotein (GMR of digoxin AUC ≥2.0 when co-administered 
with TBAJ-876 versus alone). 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 12 of 84 
 
 
Group 2 will quantify the magnitude of inhibition or induction of TBAJ-
876 on the antiretroviral regimen TLD, a fixed-dose combination of 
tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and 
dolutegravir (DTG), a regimen likely to be used in future clinical trials 
of TBAJ-876 by participants living with HIV. 
Study Design  
Group 1: All subjects will be admitted in the clinic from Day -1 until 
Day 25 for safety and PK assessments. Subjects will check-in to the 
clinic following a 21-day screening period.   
• 
On Day 1, subjects will receive a single dose of 
Midazolam (2 mg) under fasted conditions. 
• 
On Day 2, subjects will receive a single dose of 
Digoxin (0.25 mg under fasted conditions.  
• 
On Day 6 – 13, subjects will receive a single daily 
dose of 200 mg TBAJ-876 under Fed conditions.  
• 
On Day 14 – 19, subjects will receive a single daily 
dose of 165 mg TBAJ-876 under Fed conditions. 
• 
On Day 20, subjects will receive a single dose of 
Midazolam (2 mg) + a single dose of 200 mg TBAJ-
876 under fasted conditions. 
• 
On Day 21, subjects will receive a single dose of 
Digoxin (0.25 mg) + a single dose of 200 mg TBAJ-
876 under fasted conditions.  
• 
On Day 22 – 24, subjects will receive a single daily 
dose of 150 mg TBAJ-876 under Fed conditions. 
• 
On Day 25, subjects will be discharged from the clinic 
following completion of all procedures. 
• 
On Day 32, subjects will receive a follow-up phone 
call to check for AEs and any concomitant 
medications. 
 
Group 2: (To be conducted based on the Group 1 results) 
All subjects will be admitted in the clinic from Day -1, until Day 25 for 
safety and PK assessments. 
• 
On Day 1, subjects will receive a single dose of a 
Fixed Dose combination (TLD) of: Dolutegravir ( 
DTG 50 mg) + Tenofovir disoproxil fumarate (TDF 
300 mg) + Lamivudine (3TC 300 mg) under fasted 
conditions.  
• 
On Day 6 – 13, subjects will receive a single daily 
dose of 200 mg TBAJ-876 under fed conditions.  
• 
On Day 14 – 19, subjects will receive a single daily 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 13 of 84 
 
dose of 165 mg TBAJ-876 under fed conditions. - 
• 
On Day 20, subjects will receive a single dose of the 
fixed dose combination (TLD) of DTG/TDF/3TC plus 
a single dose of 200 mg TBAJ-876 under fasted 
conditions. 
• 
On Day 21 - 24, subjects will receive a single daily 
dose of 150 mg TBAJ-876 under fed conditions. 
• 
On Day 25, subjects will be discharged from the clinic 
following completion of all procedures. 
• 
On Day 32, subjects will receive a follow-up phone call 
to check for AEs and concomitant medications. 
Participant 
Population: 
Healthy adult male and female subjects, ages 18-55 inclusive.    
Group 1: Plan to enroll: 
• 
28 subjects 
Group 2: Plan to enroll: 
• 
16 subjects 
Investigational 
Medicinal Product, 
Dose and Mode of 
Administration: 
Group 1: 
The Investigational Medicinal Product (IMP) is TBAJ-876 5 mg/mL oral 
suspension formulation at the following doses:  
• 
200 mg administered on Day 6 - 13 under Fed conditions 
• 
165 mg administered on Day 14 - 19 under Fed conditions 
• 
200 mg administered on Day 20 - 21 under Fasted conditions 
• 
150 mg administered on Day 22 - 24 under Fed conditions 
Group 2:  
 
The Investigational Medicinal Product (IMP) is TBAJ-876 5 mg/mL oral 
suspension formulation at the following dose:  
• 
200 mg administered on Day 6 - 13 under Fed conditions 
• 
165 mg administered on Day 14 - 19 under Fed conditions 
• 
200 mg administered on Day 20 under Fasted conditions 
• 
150 mg administered on Day 21 - 24 under Fed conditions 
Interaction 
Products: 
The interaction products are: 
Group 1: 
• 
Midazolam oral syrup (2 mg) administered on Day 1 and Day 
20 under Fasted conditions 
• 
Digoxin (0.25 mg) tablets administered on Day 2 and Day 21 
under Fasted conditions. 
 
Group 2: TLD is a fixed dose combination pill composed of:  
Dolutegravir (50 mg) plus Tenofovir disoproxil fumarate (300 mg) plus 
Lamivudine (300 mg) and is commonly identified as: DTG + TDF 
+3TC. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 14 of 84 
 
• 
DTG + TDF + 3TC will be administered on Day 1 and Day 20 
under Fasted conditions. 
Criteria for Evaluation: 
Pharmacokinetic Sample Collection 
Serial blood samples will be collected at the time points defined in the Flow Chart (Section 1.2) 
to determine concentrations of:   
• 
TBAJ-876 and its metabolites (M2 and M3). 
• 
Midazolam and its metabolite 1-hydroxymidazolam 
• 
Digoxin 
• 
Dolutegravir 
• 
Tenofovir (TFV, the active moiety for which tenofovir disoproxil fumarate is a prodrug) 
• 
Lamivudine 
Safety Assessments: 
Safety assessments will be performed at the time points defined in the Flow Chart (Section 1.2). 
For all cohorts, physical examination (including heart murmurs), vital signs, electrocardiograms 
(ECGs), adverse events, hematology, serum chemistry, coagulation and urinalysis will be used 
to assess safety and tolerability. Blood and urine samples will be collected for clinical laboratory 
evaluations. Female subjects will have pregnancy testing during screening and at check-in. 
Females claiming postmenopausal status will have blood collected to measure follicle 
stimulating hormone (FSH) levels during screening. 
Given the key safety findings in the nonclinical safety studies regarding observed myocardial, 
skeletal muscle, pancreas, and minimal liver injury, it is planned to have extensive monitoring 
with emphasis on cardiovascular monitoring including 12 lead ECGs, as well as monitoring to 
evaluate potential pancreatic, hepatocellular and skeletal muscle injury. This will occur at both 
protocol-defined time points (see Schedule of Assessments and Procedures-Section 1.2) and 
whenever deemed necessary by the study investigator.  
Statistical Methods  
Analysis Population 
Safety population will include data from all subjects who received at least one dose of IMP 
and/or 1 dose of the interaction product. This population will be used to analyse the safety and 
tolerability endpoints. 
Pharmacokinetic (PK) population will include data from all subjects who received at least one 
dose of IMP and/or 1 dose of the interaction product and whose plasma concentration data is 
available. This population will be used for the presentation of plasma concentration results as 
well as PK analysis.  
All statistical reports must clearly indicate the group for the which the results are being 
summarised with a mention of the group in the report title. Demographics and other baseline 
characteristics will be summarized by safety population. Medical history and major protocol 
deviations will be listed. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 15 of 84 
 
The continuous variables will be summarized using number of eligible subjects (N), mean, 
standard deviation, median, minimum, and maximum. Frequency counts and percentages will 
be reported for categorical data. 
 
Pharmacokinetics (PK) Sample Collection and Analysis 
Group 1:  
• 
PK for Midazolam: Day 1 and Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 
and 24 hours 
• 
PK for TBAJ-876: Day 17: pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 hours 
• 
PK for digoxin Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 3), 48 (D4), 72 
(D5), 96 hours (D6 pre TBAJ-876 dose) 
• 
PK for digoxin Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (D22), 48 (D23), 72 
(D24), 96 hours (D25) 
 
Group 2:  
• 
PK for DTG, TFV, and 3TC: Day 1: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 
24 (D2), 48 (D3), 72 (D4), 96 (D5), 120 (Day 6 pre TBAJ-876 dose). 
• 
PK for TBAJ-876: Day 17: pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24 
• 
PK for DTG, TFV, and 3TC: Day 20:  pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 
(D21), 48 (D22), 72 (D23), 96 (D24), 120 (D25) 
Pharmacokinetic Analysis:  
Plasma concentrations of TBAJ-876 and interaction products will be listed by participant and 
visit details as applicable by group. Mean and individual concentrations (TBAJ-876, TBAJ-876 
metabolites, and interaction products) will be plotted versus time. 
Analysis for Group 1 will be conducted for induction potential of TBAJ-876 on the sensitive 
CYP3A4 substrate midazolam (M) and inhibition and induction potential of TBAJ-876 on the 
sensitive P-glycoprotein substrate Digoxin (D). 
TBAJ-876 will be considered a moderate inducer of either CYP3A4, if the GMR of midazolam 
AUC <0.50 when co-administered with TBAJ-876 versus alone, or P-glycoprotein, if the GMR 
of digoxin AUC <0.50 when co-administered with TBAJ-876 versus alone. TBAJ-876 will be 
considered a moderate inhibitor of P-glycoprotein if the GMR of digoxin AUC ≥2.0 when co-
administered with TBAJ-876 versus alone. These results will be used to decide whether to 
conduct of Group 2 of the study. 
To compare pharmacokinetic parameters of the interaction products with TBAJ-876 versus 
alone, analyses of variance (ANOVA) will be performed by the SAS Mixed Linear Models 
procedure. The model will include subject as a random effect and treatment (with TBAJ-876 
versus alone) as a fixed effect. Following log transformation, geometric least-squares mean 
values and 95% confidence intervals (CIs) will be tabulated for each pharmacokinetic 
parameter. GMRs and 95% CIs will be calculated for pharmacokinetic parameters of interaction 
products, with TBAJ-876 versus alone. 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 16 of 84 
 
Safety Analysis: 
The number of subjects for each cohort is expected to provide sufficient safety and tolerability. 
This study has not been formally powered for safety. 
All clinical safety data will be listed by subject.  Continuous variables will be summarized using 
sample size (N), mean, standard deviation, median, minimum, and maximum. Frequency 
counts will be reported for categorical data. 
Every cardiovascular adverse event will be listed by time point with accompanying symptoms 
and with blood pressure (BP) and heart rate (HR) measurements. 
Safety ECG results will be classified as normal or abnormal and summarized using frequency 
counts by dose group and time point of collection. HR and blood pressure values and changes 
from pre-dose will be summarized using descriptive statistics. 
Study Duration: 
Group1: The planned length of participation in the study is approximately 33 days from check-
in on Day -1 through completion of the Day 25 procedures and follow-up phone call on Day 32. 
 
Group 2: The planned length of participation in the study is 33 days from check-in on Day -1 
through completion of the Day 25 procedures and follow-up phone call on Day 32. 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 17 of 84 
 
1.2 Flow Chart 
 Schedule of Assessments & Procedures, Group 1: Midazolam, Digoxin 
 
SCR 
CHECK-
IN 
TREATMENT 
CHECK-
OUT 
FOLLOW UP  
 
DAY 
-21 
to -1 
-1 
1 
2-5 
 
6-
16 
17 
18 
19 
20 
21 
22-24 
25  
32 
EARLY 
WITHDRAWAL 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check-in 
questions 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight, 
BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV/ Hepatitis B, 
C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
pregnancy testb 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
FSHb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine 
drug/alcohol/ 
cotinine screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Labs 
hematology, 
chemistry, 
urinalysis)c 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Coagulationc 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Physical exam 
X 
X 
 
X 
 
 
 
 
 
 
 
X 
 
X 
Heart Murmurd  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Vital signs 
(blood pressure, 
pulse, 
temperature, 
respiration rate, 
and pulse 
oximetry)e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 18 of 84 
 
 
SCR 
CHECK-
IN 
TREATMENT 
CHECK-
OUT 
FOLLOW UP  
 
DAY 
-21 
to -1 
-1 
1 
2-5 
 
6-
16 
17 
18 
19 
20 
21 
22-24 
25  
32 
EARLY 
WITHDRAWAL 
Concomitant 
medication 
reviewf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Midazolam 
Doseh 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
Digoxin Dosei 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
TBAJ-876j 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
12-lead safety 
ECGsk 
 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
X 
 
X 
Plasma for PKl 
 
 
X 
X 
 
X 
 
 
X 
X 
X 
X 
 
 
SCR=screening; ECG = electrocardiogram; FSH = follicle-stimulating hormone; FU = follow up; HIV = human immunodeficiency virus; N/A = not 
applicable; PK = pharmacokinetic; SCR = screening 
a. Confinement to start at check-in (Evening of Day 1) until 24 hours after dosing on Day 25. 
b. Serum pregnancy test done at screening, check-in, and Day 25 for females only. FSH completed for perimenopausal females only. 
c. Safety laboratory assessments. The following analyses will be performed at the following timepoints: Screening, Day -1, Day 2, Day 3, 
Day 7, Day 20, Day 21, Day 22, and Day 25. 
 
• 
Hematology: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell (RBC) count, reticulocyte count, and 
platelet count. 
• 
Coagulation Tests: Activated partial thromboplastin time (aPTT2), Prothrombin time (PT2) 
• 
Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK), direct, indirect and total bilirubin, 
alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium (Na+), potassium (K+), 
chloride (CL-), lactate dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and bicarbonate, lipase, 
and amylase 
• 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN), according to FDA guidance criteria (see 
Appendix 3), the following tests should be performed: creatine phosphokinase of myocardial band (CPK-MB), trypsin like 
immunoreactivity, and cardiac troponin I.  
• 
Urinalysis: The following will be evaluated by an automated or manual urine “dipstick” method: pH, specific gravity, protein, glucose, 
ketones, bilirubin, creatinine, nitrite, sodium, urobilinogen, blood, myoglobin, leukocyte esterase. If protein, occult blood, nitrate, or 
leukocyte esterase values are out of range, a microscopic examination will be performed.  Myoglobin will be collected but results 
will not be required for dose qualification. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 19 of 84 
 
• 
Urine Drug, Cotinine, and Alcohol Screens - Urine samples will be tested for drugs of abuse (amphetamines, benzodiazepines, 
barbiturates, cannabinoids, cocaine, opiates) cotinine, and alcohol. 
d. Heart murmur: Presence of heart murmur 
e. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate, pulse oximetry) should be measured at screening, and 
check-in, Day -1. Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the defined time points 
in flowchart at study hours 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24. Furthermore, vital signs should also be taken once daily 
on Day 7 through Day 20 (6 hours after Dosing) and Day 25 or early withdrawal (must be done within 15 minutes before review of medication 
and collection of adverse experiences). Both blood pressure and heart rate should be captured simultaneously. Blood pressure and heart 
rate should be measured after subjects are in supine position for at least 2 minutes and then again after standing for at least 1 minute 
(starting with 2-hr post dose VS), except when they are supine or semi-reclined because of study procedures and/or adverse events, or as 
deemed necessary by the Investigator. 
f. 
On Day 32, follow-up questioning on concomitant medications will be completed by a phone call. 
g. Adverse events to be monitored from the time of informed consent signing throughout the study via safety assessments, observation and 
participant reporting. Specific adverse event questions will be posed daily throughout the study until Day 25 and a follow-up phone call on 
Day 32.. 
h. Midazolam Dose on Day 1 and Day 20 under fasted conditions 
i. 
Digoxin Dose on Day 2 and Day 21 under fasted conditions 
j. 
TBAJ-876 will be dosed as following: 
a. 200 mgTBAJ-876 on Day 6 - 13 under fed conditions 
b. 165 mg TBAJ-876 on Day 14 – 19 under Fed conditions 
c. 200 mg TBAJ-876 on Day 20 - 21 under fasted conditions 
d. 150 mg TBAJ-876 on Day 22 - 24 under fed conditions 
k. 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or designee. Single ECGs will be completed at 
screening, Day -1, 2, 3, 7, 20, 21, 22 on Day 25 or upon early withdrawal. Furthermore, ECGs should also be taken on Digoxin 
dosing days, on Day 2 and Day 21, at study hours 0, 0.5, 1, 2, 6, and 12 within 15 minutes of the defined time points. The pre-dose ECG 
should be completed within 90 minutes prior to dosing and all ECGs should be completed prior to blood draws. If a participant experiences 
a post-dosing QTcF >500 ms or a change-from-baseline QTcF >60 ms, after repeat testing, additional ECGs should be recorded until 
normalization or return to baseline 
l. 
Blood plasma samples will be drawn at the following timepoints: 
• 
Midazolam: Day 1 and Day 20: pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours 
• 
TBAJ-876: Day 17: pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24 hours 
• 
Digoxin:  
o 
Day 2: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 3), 48 (D4), 72 (D5), 96 (D6) hours 
o 
Day 21: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (D22), 48 (D23), 72 (D24), 96 (D25) 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 20 of 84 
 
 Schedule of Assessments & Procedures Group 2: Dolutegravir, Tenofovir disoproxil fumarate, 
Lamivudine 
 
SCR 
CHECK
-IN 
TREATMENT 
CHECK-
OUT 
FOLLOW-
UP  
 
DAY 
-21 to -
1 
-1 
1 
2-5 
 
6-16 
17 
18 
19 
20 
21-24 
25 
32 
EARLY 
WITHDRAWAL 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Check-in 
questions 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight 
BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV/ Hepatitis B, 
C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
pregnancy testb 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
FSHb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urine 
drug/alcohol/ 
cotinine screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Safety Labs 
hematology, 
chemistry, 
urinalysis)c 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
 
X 
Coagulation c 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
 
X 
Physical exam 
X 
X 
 
X 
 
 
 
 
 
 
X 
 
X 
Heart Murmurd  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Vital signs 
(blood pressure, 
pulse, 
temperature, 
respiration rate, 
and pulse 
oximetry)e 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 21 of 84 
 
 
SCR 
CHECK
-IN 
TREATMENT 
CHECK-
OUT 
FOLLOW-
UP  
 
DAY 
-21 to -
1 
-1 
1 
2-5 
 
6-16 
17 
18 
19 
20 
21-24 
25 
32 
EARLY 
WITHDRAWAL 
Concomitant 
medication 
reviewf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DTG+TDF+3TC 
Doseh 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
TBAJ-876i 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
12-lead safety 
ECGsj 
X 
X 
 
X 
X 
 
 
 
X 
X 
X 
 
X 
Plasma k 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
SCR=Screening; ECG = electrocardiogram; FSH = follicle-stimulating hormone; FU = follow up; HIV = human immunodeficiency virus; N/A = 
not applicable; PK = pharmacokinetic; SCR = screening    
a. Confinement to start at check-in (Evening of Day -1) until 24 hours after dosing on Day 24. 
b. Serum pregnancy test done at screening and at check-in for females only. FSH completed for perimenopausal females only. 
c. Safety laboratory assessments. The following analyses will be performed on Screening, Day -1, 2, 7, 20, 21, and 25.  
 
• 
 Hematology: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell (RBC) count, reticulocyte count, and 
platelet count. 
• 
Coagulation Tests: Activated partial thromboplastin time (aPTT2), Prothrombin time (PT2) 
• 
 Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine phosphokinase (CPK), direct, indirect and total 
bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), sodium (Na+), 
potassium (K+), chloride (CL-), lactate dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total protein, magnesium, and 
bicarbonate, lipase, and amylase 
• 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN), according to FDA guidance criteria (see 
Appendix 3), the following tests should be performed: creatine phosphokinase of myocardial band (CPK-MB), trypsin 
like immunoreactivity, and cardiac troponin I.   
• 
Urinalysis: The following will be evaluated by an automated or manual urine “dipstick” method: pH, specific gravity, protein, 
glucose, ketones, bilirubin, creatinine, nitrite, sodium, urobilinogen, blood, myoglobin, leukocyte esterase. If protein, occult 
blood, nitrate, or leukocyte esterase values are out of range, a microscopic examination will be performed.  Myoglobin will be 
collected but results will not be required for dose qualification. 
• 
Urine Drug, Cotinine, and Alcohol Screens - Urine samples will be tested for drugs of abuse (amphetamines, benzodiazepines, 
barbiturates, cannabinoids, cocaine, opiates) cotinine, and alcohol. 
d. Heart murmur: Presence of heart murmur 
e. Vital signs (blood pressure, heart rate [pulse], temperature, and respiration rate) should be measured at screening, check-in, and Day -
1. Vital sign measurements should be taken within 90 minutes prior to dosing and within 15 minutes of the defined time points in flowchart 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 22 of 84 
 
at study hours 0, 1, 6, and 12 on Days 1, 6, and 20. Furthermore, vital signs should also be taken once daily on Day 2 through Day 5 
and Day 7-19 and Day 21-25 or early withdrawal (must be done within 15 minutes before review of medication and collection of adverse 
experiences). Both blood pressure and heart rate should be captured simultaneously. Blood pressure and heart rate should be measured 
after subjects are in a seated position for 2 minutes and then again after standing for 1 minute, except when they are supine or semi-
reclined because of study procedures and/or adverse events, or as deemed necessary by the Investigator. 
f. 
On Day 32, follow-up questioning on concomitant medications AEs will be completed by a phone call. 
g. Adverse events to be monitored from the time of informed consent signing throughout the study via safety assessments, observation, 
and participant reporting. Specific adverse event questions will be posed daily throughout the study until Day 25 and a follow-up phone 
call on Day 32.  
h. DTG (50 mg) +TDF (300 mg) + 3TC (300 mg) on Day 1 and Day 20 under fasted conditions 
i. 
TBAJ-876 will be dosed as follows:   
a. 200 mg TBAJ-876 on Day 6 - 13 under Fed conditions  
b. 165 mg TBAJ-876 on Day 14 - 19 under Fed conditions 
c. 200 mg TBAJ-876 on Day 20 under fasted conditions 
d. 150 mg TBAJ-876 on Day 21 - 24 under Fed conditions 
j. 
12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or designee. Single ECGs will be completed at 
screening, Day -1, 2, 7, 20, 21, and 25 or upon early withdrawal. The pre-dose ECG should be completed within 20 minutes prior to 
the pre-dose blood draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline QTcF >60 ms, after 
repeat testing, additional ECGs should be recorded until normalization or return to baseline. 
k. Blood plasma samples will be drawn at the following timepoints: 
a. TLD: Day 1:  pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 (D2), 48 (D3), 72 (D4), 96 (D5), 120 (D6) 
b. TBAJ-876: Day 17: pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24 
c. TLD: Day 20: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24 (D21), 48 (D22), 72 (D23), 96 (D24), 120 (D25) 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 23 of 84 
 
2 
Introduction 
2.1 Background 
This study will be conducted in accordance with the protocol, International Good Clinical Practice 
(GCP) Guidelines, the ethical principles that have their origin in the Declaration of Helsinki and 
the applicable regulatory requirement(s). 
A brief overview of available confidential information regarding TBAJ-876 is summarized below 
from the Investigator’s Brochure1 (IB) Unless noted otherwise, the TB Alliance provided the 
information in this introduction. 
2.2 Tuberculosis and Rationale for New Medication 
Current tuberculosis (TB) treatment regimens are lengthy in duration and involve multi-drug 
therapy. High rates of noncompliance are common, which often result in increased mortality and 
chronic, infectious, drug-resistant cases. The present TB epidemic and treatment conditions 
demonstrate the clear need for new TB drugs and drug regimens for patients with drug-sensitive 
or drug-resistant TB that are safe and well tolerated and will shorten the overall treatment duration 
required for cure. In addition, new TB drugs and regimens should be affordable, easy to adopt 
and implement, suitable for pediatric use and for co-administration with antiretroviral therapy in 
individuals co-infected with Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus 
(HIV).  
Bedaquiline (BDQ) is a first-in-class diarylquinoline (DARQ) TB drug approved by the U.S. Food 
and Drug Administration (FDA) for use as part of a combination therapy in adults with pulmonary 
multidrug-resistant tuberculosis (MDR TB) when an effective treatment regimen cannot otherwise 
be provided. TBAJ-876 is a preclinical drug candidate from the TB Alliance’s efforts to develop a 
safer DARQ with the potential to safely deliver superior efficacy to BDQ, as part of novel TB 
treatment regimens. Current data suggest that TBAJ-876 could contribute to a new TB regimen 
with utility for both drug-sensitive and drug-resistant TB and could have significant advantages 
over BDQ. In particular, TBAJ-876 demonstrates a low risk of corrected QT (QTc) prolongation 
(whereas QTc prolongation is observed with BDQ) and lower minimal inhibitory concentrations 
(MICs) against Mtb, including strains with mutations causing reduced susceptibility to BDQ. In 
preclinical models of TB, lower doses of TBAJ-876 demonstrate superior efficacy as monotherapy 
and within regimens when compared to BDQ given at standard doses. Taken together, these 
attributes may allow TBAJ-876 to safely deliver superior efficacy compared to BDQ.  
2.3 Preclinical Studies 
 Primary pharmacology 
In primary pharmacology studies, TBAJ-876 had clear and potent anti-mycobacterial activity in 
vitro and in animal models and provided faster time to sterilization in relapsing mouse models, 
than did similar BDQ containing regimens; therefore, it is a good candidate for clinical 
investigation. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 24 of 84 
 
 Safety Assessment 
2.3.2.1 Toxicology 
The toxicological profile of TBAJ-876 was characterized in rats and dogs including two pivotal 
Good-Laboratory-Practice (GLP)-compliant 13-week toxicity studies. In the 13-week toxicity 
studies, safe TBAJ-876 dose levels and systemic exposures for TBAJ-876 and several of its 
metabolites were identified. This information was used to select a safe starting dose, identify 
potential adverse effects in human subjects, and inform the dose-escalation schedule and clinical 
safety monitoring plan in the first clinical study. 
In rats dosed for 13 weeks, the dose-limiting toxicities were diarrhea and skeletal muscle damage. 
Microscopically, skeletal muscle fiber degeneration/necrosis was present in multiple muscles of 
about 1/3rd of the rats after 13 weeks at 25 mg/kg/day or after up to 16 days at 60 mg/kg/day but 
in no rat after 13 weeks at 10 mg/kg/day. Muscle damage was accompanied by changes in 
several clinical chemistry biomarkers, e.g., by very high serum creatine kinase (CK), AST, and 
ALT activities and high serum potassium and phosphorus concentrations. Muscle damage was 
reversible, as it was absent after a 10- or 13-week recovery period.   
In dogs dosed for 13 weeks, no dose-limiting toxicity was seen, but cardiac muscle damage was 
present microscopically (as cardiac muscle fiber necrosis/infiltrate) in all but one dog at 15 
mg/kg/day but in no dogs at ≤7.5 mg/kg/day. While this can be an incidental background finding 
in dogs, the high incidence of this finding at 15 mg/kg/day was considered to be related to TBAJ-
876, in part because the finding was accompanied by an increase in serum troponin I 
concentration. Cardiac muscle damage was reversible, as it was absent after a 13-week recovery 
period.  
Various other TBAJ-876-related findings were seen in one or both species. These included: 
• 
Microscopic findings in the glandular mucosa of the stomach in both species,  
• 
Effects on intestinal function (diarrhea) in both species,  
• 
Effects on the liver in both species,  
• 
Decreased hematopoiesis in dogs,  
• 
Effects on the incisors in rats, 
• 
Effects on the lacrimal glands in rats, 
• 
Increased serum amylase concentration in dogs.   
In the glandular stomach mucosa, hyperplasia was seen in several rats after 13 weeks at 
25 mg/kg/day or after two weeks at 60 mg/kg/day. This finding was reversible, as it was absent 
after a 10- or 13-week recovery period. Degeneration/necrosis of the glandular mucosa was seen 
in two rats after 13 weeks at 25 mg/kg/day and several rats after two weeks at 60 mg/kg/day. At 
the end of the recovery period, degeneration/necrosis also was present in two rats that had been 
given TBAJ-876 for 13 weeks at 25 mg/kg/day. Finally, erosion of the pyloric mucosa was 
observed in one rat after 13 weeks at 25 mg/kg/day.  
In dogs, minimal to moderate degeneration/atrophy of the fundic glands in the stomach was seen 
in a preliminary non-GLP study after 2 weeks at 15 or 45 mg/kg/day. This was characterized by 
loss of chief cells with overall atrophy of glands, dilated glands with attenuated epithelium, and 
occasional glands with luminal cell debris. When minimal, the primary alteration was individual 


TMP-C-SOP01-B V1.0 30-JAN-2019 
CONFIDENTIAL 
Page 25 of 84
TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
cell necrosis of chief cells with infrequent, minimally dilated glands. The grade of fundic gland 
degeneration/atrophy increased with dose level. Stomach findings were not seen in 8 dogs given 
daily oral doses of TBAJ-876 for 13 weeks at 15 mg/kg (the highest dose level tested). One 
possible explanation is that the 2-week study used TBAJ-876 free base, while the 13-week study 
used TBAJ-876 tartrate.  
Diarrhea was seen in rats given two doses of TBAJ-876, approximately 24 hours apart, at ≥ 500 
mg/kg in a micronucleus study and also during the second week of dosing at 60 mg/kg/day in the 
13-week study. At 60 mg/kg/day, diarrhea was accompanied by anogenital staining and 
dehydration, and contributed to the decision to stop dosing early at this dose level. Diarrhea 
resolved when dosing stopped. In dogs in the 13-week study, the frequency of discolored, mucoid 
or with mucous, watery, and/or soft feces was greater at 15 mg/kg/day than in the control group, 
but this difference was not clearly related to TBAJ-876.
Effects on the liver in rats were limited to single-cell vacuolar degeneration or necrosis of 
hepatocytes and/or vacuolation of periportal hepatocytes in a few females after 16 days at 60 
mg/kg/day. This finding resolved when dosing stopped, although at the end of the recovery phase, 
single cell necrosis was present in one male that had been given TBAJ-876 for 16 days at 60 
mg/kg/day. In dogs dosed for 13 weeks, hepatocellular vacuolation with greater mean liver weight 
and lower mean serum triglycerides concentration was present at all dose levels. At the lowest 
dose level (25 mg/kg/day), these findings were not considered adverse because they were not 
associated with clinical pathologic or microscopic evidence of hepatocellular degeneration or 
necrosis. At ≥7.5 mg/kg/day, mean serum ALT activity was increased after 4 and 13 weeks of 
dosing, but there still was no microscopic evidence of hepatocellular injury.   
Evidence of decreased hematopoiesis was seen in dogs dosed for 13 weeks, where the incidence 
and average grade of decreased cellularity in sternal bone marrow was greater at 15 mg/kg/day. 
This microscopic finding was not associated with any changes in peripheral blood cell counts and 
was absent after a 13-week recovery period. 
In female dogs, mean serum amylase concentration was slightly greater after 4 and 13 weeks of 
dosing at 15 mg/kg/day, without associated microscopic findings in the pancreas. 
Two findings related to TBAJ-876 were seen only in rats and are of questionable relevance for 
humans: 
•
Degeneration/necrosis of ameloblasts was present in the incisors of rats dosed for
13 weeks. At 25 mg/kg/day, four rats also had acute inflammation in the nasal cavity
(near tooth root), one rat also had pulp cavity necrosis, another had moderate
periodontal inflammation, and a third had mild acute gingivitis. These dental findings
were reversible, as they were absent at the end of the 13-week recovery period.
While the effects on incisors were clearly adverse in rats, it is unclear if these findings
are relevant for human subjects, because the incisors of rats grow continuously
throughout life, unlike human teeth. The teeth were not examined microscopically in
dogs dosed for 13 weeks; however, there was no clinical evidence of an effect on
teeth, nor were there any findings involving the teeth or oral cavity at necropsy.
•
In the lacrimal glands of rats dosed for 13 weeks, the average grade of acinar cell
alteration (characterized by histologic characteristics of Harderian gland) was
greater at all dose levels. After 13 weeks at 25 mg/kg/day, a few rats also had
lacrimal gland atrophy. The differences in grade showed evidence of reversing when
dosing stopped. Acinar cell alteration is a rodent specific finding, and so it is unclear


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 26 of 84 
 
if an increase in this finding implies a risk for human subjects. There were no effects 
on lacrimal glands in dogs dosed for 13 weeks. 
Pharmacokinetic exposures in the toxicity studies are summarized in Table 1. 
2.3.2.2 Safety Pharmacology  
Secondary and safety pharmacology studies suggest that, at the dose levels proposed for 
evaluation in human subjects, TBAJ-876 is unlikely to produce adverse effects due to off target 
pharmacologic activity or to adversely affect the function of important organ systems. 
Cardiovascular Function 
In surgically instrumented dogs given repeated doses of TBAJ-876 for 12 days at escalating dose 
levels up to 30 mg/kg/day, there was no effect on blood pressure, heart rate, pulse rate (PR), or 
QT interval duration, QRS complex duration, or qualitative aspects of the electrocardiogram 
(ECG).  There were slight decreases in QTc interval duration at 30 mg/kg/day, but these appeared 
to be driven by slight increases in body temperature and were not large enough to be considered 
adverse; therefore, the no observed adverse event level (NOAEL) for effects on cardiovascular 
function was 30 mg/kg/day. Plasma exposure to TBAJ-876 and its M2 and M3 metabolites after 
the third dose at the NOAEL are summarized in Table 1. 
In a 13-week general toxicology study in dogs, oral administration of TBAJ-876 tartrate at doses 
of 2.5, 7.5, and 15 mg/kg/day did not have any adverse effects on ECG rhythm, morphology, or 
quantitative measurements; therefore, the 13-week NOAEL for effects on cardiovascular function 
was 15 mg/kg/day. Plasma exposure to TBAJ-876 and its M2 and M3 metabolites after the last 
dose at the cardiovascular NOAEL are summarized in Table 1. 
Nervous System Function 
As part of the 13-week general toxicology study in which rats were given daily oral doses of 
TBAJ-876, functional observational battery (FOB) testing was conducted on 10 rats/sex at 
approximately 8 hours after the 13th dose. Rats tolerated daily oral doses of TBAJ-876 for 
13 weeks at 10 or 25 mg/kg but not at 60 mg/kg, where dosing was stopped after 16 days due 
to toxicity. There were no differences between control and treated rats in FOB test results; 
therefore, 2-week NOAEL for effects on nervous system function was 60 mg/kg/day. Plasma 
exposure to TBAJ-876 and its M2 and M3 metabolites after the last dose at the nervous system 
NOAEL are summarized in Table 1. 
Respiratory Function 
In rats given daily oral doses of TBAJ-876 for 7 days at 10, 30, or 75 mg/kg and evaluated by 
plethysmography, there was no effect on respiratory function at ≤30 mg/kg/day. At 75 mg/kg/day, 
TBAJ-876 resulted in slight, recoverable, increases in respiratory rate and tidal volume (and 
therefore in minute volume), which were smaller after the 7th dose than after the first dose and 
had resolved completely within 4 days after the last dose. These effects on respiratory function 
were too slight to be considered adverse; therefore, the 7-day NOAEL for effects on respiratory 
function was 75 mg/kg/day. Plasma exposure to TBAJ-876 and its M2 and M3 metabolites after 
the 8th and last dose at the respiratory NOAEL are summarized in Table 1.


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 27 of 84 
 
Table 1 
Plasma Exposure to TBAJ-876 and Metabolites in Toxicity and Safety Pharmacology Studies 
 
 
Study 
Duration 
NOAEL 
LOAEL 
Higher Dose 
NOAEL 
Dose 
(mg/kg) 
NOAEL 
AUC0-24A, 
(ug∙h/mL) 
NOAEL  
CmaxA,  
(ug∙h/mL) 
LOAEL 
Dose, 
(mg/kg) 
LOAEL 
AUC0-24A,  
(ug∙h/mL) 
LOAEL  
CmaxA,  
(ug∙h/mL) 
Higher 
Dose 
(mg/kg) 
Higher 
AUC0-24A, 
(ug∙h/mL) 
Higher  
CmaxA,  
(ug∙h/mL) 
Rat / 
Tox 
3-months 
10 
876: 8.4 
M2: 1.6 
M3: 5.2 
876: 0.7 
M2: 0.1 
M3: 0.3 
25 
876: 29.6 
M2: 10.8 
M3: 25.4 
876: 2.1 
M2: 1.0 
M3: 2.3 
60E 
876: 64.6 
M2: 6.3 
M3: 47.5 
876: 4.1 
M2: 0.4 
M3: 2.2 
Dog / 
Tox 
2-weeksB 
5 
876: 7.6 
M2: NA 
M3: 14.7 
876: 0.6 
M2: NA 
M3: 0.8 
15 
876: 14.1 
M2: NA 
M3: 55.0 
876: 0.9 
M2: NA 
M3: 2.8 
45 
876: 22.7 
M2: NA 
M3: 128 
876: 1.8 
M2: NA 
M3: 6.4 
Dog / 
Tox 
3-months 
2.5 
876: 10.0 
M2: 1.8 
M3: 17.3 
876: 0.6 
M2: 0.08 
M3: 0.8 
7.5 
876: 18.1 
M2: 6.9 
M3: 50.1 
876: 1.3 
M2: 0.3 
M3: 2.3 
15 
876: 25.0 
M2: 15.2 
M3: 102.5 
876: 1.7 
M2: 0.7 
M3: 4.7 
Rat/ 
NS SP 
13-daysC 
60 
876: 64.6 
M2: 6.3 
M3: 47.5 
876: 4.1 
M2: 0.4 
M3: 2.2 
ND 
(>60) 
ND 
ND 
Rat / 
Resp. 
SP 
8-days 
75 
876: 92.1 
M2: 0.7 
M3: 16.2 
876: 6.2 
M2: 0.04 
M3: 0.9 
ND 
(>75) 
ND 
ND 
Dog /  
CV SP 
12-daysD 
30 
876: 26.9 
M2: 3.4 
M3: 33.5 
876: 2.3 
M2: 0.2 
M3: 1.6 
ND 
(>30) 
ND 
ND 
NOAEL = No Observed Adverse Effect Level; LOAEL = Lowest Observed Adverse Effect Level NC = Not calculated; NA = Not assessed; ND = Not 
determined;  NS = Nervous System; Resp. = Respiratory; SP = safety pharmacology study; CV = Cardiovascular 
 
AExposure (AUC0-24 and Cmax) is presented after the last dose of the study 
BThe 2-week dog toxicity study with TBAJ-876 was non-GLP 
CNervous system function safety pharmacology study was conducted within the 3-month toxicity study 
DDoses were administered in an escalating fashion from 3 mg/kg (Days 1-4), 10 mg/kg (Days 5-8), and 30 mg/kg (Days 9-12) 
ERats were administered TBAJ-876 for 16 days then dosing was stopped due to toxicity. 


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2.3.2.3 Potential adverse effects in human subjects 
Table 1 summarizes pharmacokinetic exposures in nonclinical toxicity and safety pharmacology 
studies. As discussed in Section 2.6, a potential clinical dose of TBAJ-876 is 100 mg QD for eight 
weeks. Based on a mathematical model developed using data from the first-in-human study, 
predicted mean values of AUC0-24 for TBAJ-876 and M3 at the end of treatment are 9.90 and 1.47 
μg.h/mL, and the corresponding predicted mean values of Cmax are 0.596 and 0.063 μg/mL. In 
humans, the concentration of the parent species, TBAJ-876, is much greater than that of the M3 
metabolite; whereas in rats, the two species generally have similar exposures, and in dogs M3 
exposures are higher. Considering TBAJ-876 alone, predicted human exposures are 
approximately equivalent to slightly higher than the NOAEL from the toxicity studies and 
substantially lower than the NOAEL from the safety pharmacology studies in Table 1. The 
predicted M3 metabolite exposures are lower to substantially lower than the NOAELs from the 
toxicology and safety pharmacology studies. Considering the sum of TBAJ-876 and M3 
metabolite exposures, predicted human exposures are less than all NOAEL exposures.  
Based on the nonclinical safety studies, human subjects were monitored in a first-in-human 
clinical study for the following potential effects:   
• 
Myocardial damage (seen in dogs) by way of clinical chemistry biomarkers  
• 
Skeletal muscle myopathy (seen in rats) by way of clinical chemistry biomarkers and 
clinical signs of muscle pain or weakness 
• 
Damage to the stomach mucosa (seen in both species) by way of clinical signs of 
nausea, vomiting, or dyspepsia 
• 
Diarrhea (seen in both species) 
• 
Liver injury, both hepatocellular and biliary (seen in both species) by way of clinical 
chemistry biomarkers 
• 
Effects on hematopoiesis (seen in dogs) by way of hematology analyses 
• 
Effects on the pancreas (seen in dogs) by way of clinical chemistry biomarkers 
In animals, all of these effects were reversible when dosing stopped, and they are expected to be 
so in humans, too, if they occur. 
No studies have been done to evaluate the potential effects of TBAJ-876 reproductive function 
in male or female animals.  
The following side effects were noted in adult subjects/patients in studies of a similar drug in this 
class (bedaquiline – marketed as SirturoTM): nausea, tiredness, headache, vomiting, dizziness, 
diarrhea, liver injury, heart problems; prolongation of QTc interval, and pancreas injury. 2 
(Bedaquiline circular). 
 Pharmacokinetics and Product Metabolism in Animals  
Absorption 
Following intravenous (IV) administration, TBAJ-876 exhibited low clearance and a large volume 
of distribution (≥9.45 L/kg). The plasma disposition of TBAJ-876 in nonclinical species was 
multiexponential and due to differences in PK sampling schedule, estimates of terminal half-life 


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(t1/2) of TBAJ-876 varied widely, ranging from 5 to 12 hr (sampling out to 24 hr postdose) to 26 to 
77 hr (sampling out to 96 hr postdose). 
TBAJ-876 free base had good oral bioavailability ranging from 36% to 44% in rodents, 28% to 
80% in dogs, and 19% to 24% in monkeys, despite low permeability in the Caco-2 cell monolayer. 
Based on the efflux ratio of 0.2 in Caco-2 cells, TBAJ-876 was not a substrate of efflux pumps. 
When TBAJ-876 was orally administered as tartrate salt to nonclinical species in the fasted state, 
Cmax increased 40% to 70% and AUC0-t increased 39% to 59% in rats and dogs, whereas in 
monkeys Cmax and AUC0-t decreased 43% and 49%, respectively. 
The in vivo exposure to two active metabolites, TBAJ-876-M2 and TBAJ-876-M3, was quantified 
in the PK and toxicokinetic (TK) studies. At the NOAELs in the 13-week toxicology studies in the 
rat and dog, the steady state AUC of TBAJ-876-M3 was 0.6x and 1.8x of parent AUC, 
respectively, while TBAJ-876-M2 was present at lower concentrations representing 0.2x of parent 
AUC in both species. Female rabbits also showed a similar profile after receiving a single dose of 
TBAJ-876 0.6x and 0.02x to 0.3x of parent AUC, respectively. There was no marked sex-related 
difference in the systemic exposure to TBAJ-876, TBAJ-876-M3, or TBAJ-876-M2 in rats and 
dogs. 
In mice following the last dose of 4-week dosing at 3.125 mg/kg, steady state plasma exposure 
to TBAJ-876 and metabolites was approximately 0.4x of that of BDQ and metabolite at 25 mg/kg. 
After 6 weeks dosing in a mouse model of chronic TB, 3.125 mg/kg TBAJ-876 showed superior 
efficacy to 25 mg/kg BDQ indicative of TBAJ-876 being more potent than BDQ (Table 2). TBAJ-
876-M3, TBAJ-876-M2, and BDQ-M2 AUC0-24 was 5x of parent AUC0-24h. 


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Table 2 
Plasma Exposure to TBAJ-876 and Metabolites vs. BDQ and BDQ-M2 
Following 4-week Repeated Oral Administration to Mice 
Dose 
Cmax 
AUC0-24h 
Analyte 
(µg/mL) 
(hr*µg/mL) 
3.125 mg/kg/day TBAJ-876 
 
 
TBAJ-876 
0.47 
4.1 
TBAJ-876-M2 
0.93 
20.2 
TBAJ-876-M3 
1.0 
22.1 
25 mg/kg/day BDQ 
 
 
BDQ 
1.9 
10.6 
BDQ-M2 
2.8 
57.2 
 
Distribution  
TBAJ-876 and its metabolite TBAJ-876-M3 were not significantly distributed to red blood cells. 
TBAJ-876 and TBAJ-876-M3 were highly protein-bound in mouse, rat, dog, monkey, and human 
plasma (≥99.8%) and exhibited a species-independent protein binding. At steady state, high 
concentrations of TBAJ-876 and TBAJ-876-M3 were observed in the mouse lung at 2 hr and 24 
hr postdose with the lung to plasma concentration ratio for TBAJ-876 and TBAJ-876-M3 in the 
range of 5 to 7 and 12 to 20, respectively. 
Metabolism 
TBAJ-876 and TBAJ-876-M3 were relatively stable metabolically with TBAJ-876 showing a half-
life of >240 min in rat, dog, and human liver microsomes and a half-life of 114 and 31 min in 
monkey and mouse liver microsomes, respectively, and TBAJ-876-M3 showing a half-life of >240 
min in mouse, rat, dog, monkey, and human liver microsomes. The in vitro metabolic stability 
result is consistent with low in vivo clearance observed. TBAJ-876 was mainly metabolized by 
recombinant human CYP3A4 followed by CYP2A6, while both CYP3A4 and CYP2A6 play an 
equal role in the metabolism of TBAJ-876-M3. The Km and Vmax values of TBAJ-876 were 43.4µM 
and 299 pmol/min/mg, respectively, in human liver microsomes and 2.20µM and 4.06 
pmol/min/pmol P450 for recombinant human CYP3A4. 
In vitro metabolic profile in liver microsomes from nonclinical species and human concluded that 
TBAJ-876-M3 was the major metabolite and there were no human unique metabolites. 
TBAJ-876 showed no or limited inhibition of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 
activities in human liver microsomes with IC50 >50 µM. TBAJ-876-M3 at 30 µM (i.e., nearly 300x 
the predicted mean TBAJ-876-M3 Cmax in humans at the end of eight weeks of treatment with the 
potential clinical TBAJ-876 dose of 100 mg) caused a maximum 78% inhibition of CYP2C19 
activity in human liver microsomes. Therefore, it can be concluded that the risk for TBAJ-876 and 
TBAJ-9876-M3 to cause PK drug interactions in humans by inhibition of the major drug 
metabolizing enzymes is low. 
The major metabolite TBAJ-876-M3 did not activate AhR, CAR, or PXR nuclear receptors in vitro. 
However, TBAJ-876 at 1 µM (i.e., approximately 1x the predicted mean TBAJ-876 Cmax in humans 


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at the end of eight weeks of treatment with the potential clinical dose of 100 mg) induced CYP3A4 
mRNA in one of three lots of human hepatocytes tested.  
In vitro transporter inhibition studies showed that TBAJ-876 at 1 µM did not cause notable 
inhibition of OAT1, OAT3, OCT2, OATP1B1, OATP1B3, MATE1, or MATE2-K. The IC50 for BCRP 
cannot be determined due to insufficient inhibition over a concentration range of 0.5 to 30 µM. 
The IC50 for P-gp was determined to be 5.08 µM based on nominal concentrations, equivalent to 
approximately 2.30 µM after taking into account the non-specific binding. 
2.4 Clinical Findings 
 Safety 
A Phase 1 study combined single ascending dose (SAD) study with food-effect cohort and 
multiple ascending dose (MAD) clinical study to evaluate the safety, tolerability, and 
pharmacokinetics of TBAJ-876 in healthy subjects is ongoing. Dosing is completed however some 
subjects are still being followed up for safety and PK. (Protocol TBAJ-876-CL001).  Below is a 
summary of the blinded safety data as of the most recent review of the data. 
The first subject was dosed on 08Jun20. The SAD study included 7 Cohorts of 8 subjects (6 on 
study drug, 2 on placebo) each. The doses studied were: 10, 25, 50, 100, 200, 400 and 800 mg 
under fasted conditions and then subjects were followed from 14 days and up to 10 weeks during 
which time they returned to the clinic for safety and PK. The MAD study included 3 cohorts (9 on 
study drug and 3-5 on placebo).  The doses studied were: 25, 75 and 200 mg for 14 days under 
fed conditions.  Subjects were then followed for up to 18 weeks during which time they returned 
to the clinic every 3 weeks for safety (including safety labs, ECGs) and PK.  
Prior to escalating to the next dose both for the SAD and MAD, a meeting was held to review all 
the safety and PK data. Review of the blinded safety data showed that TBAJ-876 was generally 
safe and well tolerated at single doses between 10 and 800 mg and 14-day dosing with 25, 75 
and 200 mg.  There were no serious or severe AES.  Most of the AEs were mild and all resolved. 
There were very few clinically significant changes in clinical safety tests, and all resolved. There 
were also no reported clinically significant QT prolongations based on ECG review.  
AEs of interest, based on nonclinical findings, included myocardial damage, skeletal muscle 
injury, gastrointestinal irritation, elevated pancreatic enzymes, elevated liver enzymes, and 
cytopenia. Observations related to these AEs in the first-in-human study, where the data are still 
blinded, were: 
• 
Myocardial: there was no evidence of myocardial toxicity 
• 
Skeletal muscle:  
o 2 events of rhabdomyolysis, secondary to strenuous physical activity, not related, 
both resolved. 
o A few events of muscle pain, all resolved. 
• 
GI: only mild to moderate GI adverse events 
• 
Liver: no signal identified 
• 
Pancreas: no signal identified 
 


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 Pharmacokinetics 
Concentrations of the two metabolites, M2 and M3, as well as of the parent TBAJ-876 were 
measured in the SAD and the MAD. Because of M2’s low exposures, the focus is centered on 
the parent and M3. 
TBAJ-876 and M3 exposures were approximately dose proportional in both the SAD study, over 
a dose range of 10 – 800 mg, and the MAD study, over a dose range of 25 – 200 mg QD for 14 
days.  
The food effect of TBAJ-876 was studied in the SAD study using a single 100 mg dose. After a 
high-fat breakfast, the AUC and Cmax of TBAJ-876 increased by approximately 60% and 100% 
respectively, while M3 AUC and Cmax decreased by approximately 30% and 40%, respectively. In 
the MAD study, TBAJ-876 was administered daily with a high-fat breakfast. 
TBAJ-876 and M3 exhibited multi-compartmental pharmacokinetics with long terminal half-lives 
of approximately 60 and 20 days, respectively. Consequently, TBAJ-876 and M3 accumulate with 
multiple dosing. 
Table 3 shows mean Cmax and AUC0-24 of TBAJ-876 and M3 after the 1st and 14th doses in the 
MAD study. 


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Table 3 
Mean Cmax and AUC0-24 of TBAJ-876 and M3 in the MAD study. 
Dose 
(mg) 
TBAJ-876 
M3 
Cmax (μg/mL) 
AUC0-24 (μg.h/mL) 
Cmax (μg/mL) 
AUC0-24 (μg.h/mL) 
Day 1 
Day 14 
Day 1 
Day 14 
Day 1 
Day 14 
Day 1 
Day 14 
25 
0.096 
0.148 
0.938 
1.67 
0.0013 
0.0106 
0.015 
0.209 
75 
0.322 
0.401 
3.010 
4.25 
0.0040 
0.0354 
0.068 
0.650 
200 
0.873 
1.160 
7.270 
12.90 
0.0110 
0.0858 
0.175 
1.620 
Note: TBAJ-876 was administered daily with a high-fat breakfast. 
 
2.5 Rationale for Drug-Drug Interaction Studies 
Interactions between an investigational new drug and other drugs should be defined during drug 
development, as part of an adequate assessment of the drug’s safety and effectiveness. The 
objective of drug-drug interaction studies is to determine whether potential interactions between 
the investigational drug and other drugs exist and, if so, whether the potential for such interactions 
indicates the need for dosage adjustments, additional therapeutic monitoring, a contraindication 
to concomitant use, or other measures to mitigate risk. 
In vitro studies of TBAJ-876 identified the potential for CYP3A4 induction and P-gp inhibition. In 
particular, TBAJ-876 at 1 μM, approximately equal to the predicted mean Cmax in humans after 90 
days of dosing at a potential clinical dose of 100 mg, induced CYP3A4 mRNA in one of three lots 
of human hepatocytes tested. A positive signal for induction of CYP3A4 in this assay may also 
indicate potential induction of P-gp. However, in another assay a signal for potential inhibition of 
P-gp was observed, with an IC50 of 5.08 μM. A dose of 100 mg of TBAJ-876 would yield a value 
of Igut/IC50 > 10 and thus satisfy the criterion for potentially inhibiting P-gp in vivo according to 
FDA’s guidance “In Vitro Drug Interaction Studies —Cytochrome P450 Enzyme- and Transporter-
Mediated Drug Interactions” of January 2020. 
Because of potential interactions with TBAJ-876, the pharmacokinetics of midazolam, a CYP3A4 
substrate, and digoxin, a P-gp substrate, will be studied before and after two weeks of daily dosing 
with TBAJ-876. Depending on the outcome of this investigation, a similar investigation may be 
undertaken with the antiretroviral regimen TLD (tenofovir disoproxil fumarate (TDF), lamivudine 
(3TC), dolutegravir (DTG)). This regimen is likely to be used in future clinical trials of TBAJ-876 
by participants with HIV. DTG is a substrate of CYP3A4 and P-gp, and TDF is a substrate of P-
gp.  
The following sections contain safety information excerpted from the Prescribing Information for 
midazolam syrup, digoxin, and TLD tablets listed in the reference section of the protocol. 
Midazolam Syrup3  
Midazolam hydrochloride (HCl) syrup is indicated for use as a single dose (0.25 to 1 mg/kg with 
a maximum dose of 20 mg) for preprocedural sedation and anxiolysis in pediatric patients. 
Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant.  
Adverse events: In a randomized, double-blind, parallel-group trial, the most commonly reported 
adverse events among patients during the premedication period (before the introduction of 
anesthesia) were emesis, nausea, laryngospasm, and sneezing/rhinorrhea. 


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Other adverse events that have been reported in the literature with the oral administration of 
midazolam (not necessarily Midazolam Syrup), are listed below. The incidence rate for these 
events was generally <1%. 
Respiratory: apnea, hypercarbia, desaturation, stridor. 
Cardiovascular: decreased systolic and diastolic blood pressure, increased heart rate. 
Gastrointestinal: nausea, vomiting, hiccoughs, gagging, salivation, drooling. 
Central nervous system: dysphoria, disinhibition, excitation, aggression, mood swings, 
hallucinations, adverse behavior, agitation, dizziness, confusion, ataxia, vertigo, dysarthria. 
Special senses: diplopia, strabismus, loss of balance, blurred vision. 
The midazolam syrup label carries a boxed warning for risks with concomitant use of 
benzodiazepines and opioids. 
Pregnancy Category: Midazolam is rated Pregnancy Category D. Although midazolam HCl syrup 
has not been studied in pregnant patients, an increased risk of congenital malformations 
associated with the use of benzodiazepine drugs (diazepam and chlordiazepoxide) have been 
suggested in several studies.  
Digoxin4  
Digoxin tablets are indicated for the treatment of mild to moderate heart failure in adults and 
indicated for the control of ventricular response rate in adults with chronic atrial fibrillation.  
Adverse events: In patients who are being treated with digoxin for heart failure or certain types of 
irregular heartbeat the most common (1% to 10%) adverse events include: 
Cardiovascular: arrhythmia, conduction disturbances, PR prolongation and sinus bradycardia. 
Gastrointestinal: nausea, vomiting, loss of appetite, lower stomach pain and diarrhea. 
Central nervous system: dizziness, drowsiness, and headache 
Other adverse events that are unlikely but serious may occur with digoxin include: weakness, 
mental/mood changes, vision changes (such as blurred or yellow/green vision) and 
enlarged/tender breasts in males.  
Pregnancy Category: Digoxin is rated Pregnancy Category C. Underlying maternal condition (e.g., 
heart failure, atrial fibrillation) may increase risk of adverse pregnancy outcomes. 
Dolutegravir/lamivudine/tenofovir (DTG/3TC/TDF)5  
DTG/3TG/TDF (TLD) is a fixed dose combination tablet containing 50 mg dolutegravir, 300 mg 
lamivudine and 300 mg tenofovir disoproxil fumarate. It is indicated for the treatment of human 
immunodeficiency virus (HIV) infection in adults and adolescents weighing at least 30 kg. As of 
2019, it is listed by the World Health Organization (WHO) as first line treatment for adults.6 
Adverse events: Potential side effects of TLD include insomnia, headache, agitation, nausea, 
diarrhea, and skin rash.  


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Warnings and Precautions: Previous hypersensitivity reaction to DTG, uncontrolled diabetes, 
renal impairment (creatinine clearance <50 ml/min), liver impairment, ascites, albumin <2.8 g/dL, 
total bilirubin >50 mmol/L and encephalopathy. 
Pregnancy: In an initial study, exposure to DTG around the time of conception and during the first 
8 weeks of pregnancy was previously thought to be associated with an increased risk of neural 
tube defects in the fetus.  However, new data from two large clinical trials comparing the efficacy 
and safety of DTG and efavirenz have expanded the evidence base to suggest that the risk of 
neural tube defects are significantly lower than what the initial studies suggested.  In July 2019, 
WHO announced that DTG is safe for women of child-bearing age.6 
2.6 Rationale for the TBAJ-876 Dose Regimen 
The finding of cardiac muscle damage in the 13-week dog toxicity study (Section 2.3.2) is being 
used to guide dose selection in this and other clinical studies. Clinical doses are being selected 
to keep exposure in humans below a limit determined by exposure in the dogs at the dose of 15 
mg/kg/day where the cardiotoxicity was seen. Exposure for this purpose is quantified by the sum 
of the 24-hour AUCs of TBAJ-876 and its M3 metabolite, referred to as SAUC. The limit for the 
mean SAUC in humans is 12.8 μg.h/mL, which is 1/10th the mean SAUC in dogs after 13 weeks 
of dosing at 15 mg/kg/day. To achieve maximal efficacy, it is expected that the maximum clinical 
dose will be selected to yield exposures just below this limit. 
A 100 mg QD dose of TBAJ-876 administered for eight weeks is a projected clinical efficacious 
dose. Based on a pharmacokinetic model developed using the data from the SAD and MAD 
studies, where a suspension formulation of TBAJ-876 was used, dosing TBAJ-876 at 100 mg QD 
for eight weeks, an aspirational treatment duration, is predicted to yield a mean SAUC at the end 
of treatment of 11.4 μg.h/mL. The separate mean values of AUC0-24 for TBAJ-876 and M3 at the 
end of treatment are predicted to be 9.90 and 1.47 μg.h/mL, and the corresponding values of Cmax 
are predicted to be 0.596 and 0.063 μg/mL, which were described above for comparison with the 
exposures listed in Table 1. 
The goal for this drug-drug interaction study is to find a regimen that is expected to provide daily 
mean SAUC values close to, but not above, 12.8 μg.h/mL for a long enough duration to achieve 
a clinically relevant extent of induction, if TBAJ-876 is indeed an inducer of CYP3A4 or P-gp. The 
regimen chosen is: 
• 
Day 6 to Day 13: 200 mg TBAJ-876, fed 
• 
Day 14 to Day 19: 165 mg TBAJ-876, fed 
• 
Day 20 and Day 21 in Group 1, Day 20 in Group 2: 200 mg TBAJ-876, fasting 
• 
Day 22 to Day 24 in Group 1, Day 21 to Day 24 in Group 2: 150 mg TBAJ-876, fed 
This regimen is predicted to keep the mean SAUC between 80% and 100% of 12.8 μg.h/mL from 
Day 9 through Day 24.       
3 
Study Objectives 
3.1 Primary Objectives 
The primary objective of the study is: 


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• 
To evaluate the induction potential of TBAJ-876 on CYP3A4 and P-glycoprotein (P-gp) and 
the inhibition potential of TBAJ-876 on P-gp in healthy adult subjects. 
3.2 Secondary Objectives 
The secondary objectives of the study are: 
• 
To evaluate the effects of multiple-dose administrations of TBAJ-876 on the safety and 
tolerability of midazolam and digoxin. 
• 
To evaluate the effects of multiple-dose administration of TBAJ-876 on the safety and 
tolerability of an antiretroviral regimen (If Group 2 is conducted).   
4 
Study Design 
4.1 Summary of Study Design 
This study is a two-part, open-label drug-drug interaction study conducted in one study center in 
the United States. Two groups are planned, Group 1 and Group 2.  Group 2 will be conducted 
based on the Group 1 results. 
Group 1 will assess the induction potential of TBAJ-876 on the sensitive CYP3A4 substrate 
midazolam (M) and inhibition and induction potential of TBAJ-876 on the sensitive P-glycoprotein 
substrate Digoxin (D). 
Group 2 will only be conducted if the results of Group 1 show that TBAJ-876 is a moderate 
inducer of either CYP3A4 (midazolam AUC <0.50 when co-administered with TBAJ-876) 
or P-glycoprotein (digoxin AUC <0.50 when co-administered with TBAJ-876) or a moderate 
inhibitor of P-glycoprotein (digoxin AUC ≥2.0 when co-administered with TBAJ-876. 
 
This group will quantify the magnitude of inhibition or induction of TBAJ-876 on the 
antiretroviral regimen TLD, a fixed dose combination of tenofovir disoproxil fumarate (TFD), 
lamivudine (3TC) and dolutegravir (DTG), a regimen likely to be used in future clinical 
studies of TBAJ-876 by subjects living with HIV. 
 
Safety will be assessed throughout the study for all subjects. Safety assessments will include 
physical examinations, vital signs, serial ECGs, adverse events (AEs), clinical and laboratory tests 
(including hematology, serum chemistry, coagulation, and urinalysis). 
Serial blood samples for PK will be collected at the timepoints according to the Schedule of 
Assessments & Procedures: Flow Chart (Section 1.2) and sent to a bioanalysis lab where they 
will be analysed for the for the following analytes using validated analytical methods: 
• 
TBAJ-876 and its metabolites M2 and M3 
• 
Midazolam and its metabolite 1-hydroxymidazolam 
• 
Digoxin 
• 
Dolutegravir 
• 
Tenofovir (TFV, the active moiety for which tenofovir disoproxil fumarate is a prodrug) 
• 
Lamivudine 


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4.2 Treatment Plan; Schedule of Assessments 
In both Group 1 and Group 2, the dosing regimen for TBAJ-876 is listed in Table 4. Also listed in 
the table are the doses of the interaction products, dosing schedule, and if taken under Fed or 
fasted conditions. 


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Table 4 
Investigational Medicinal Product (IMP) Details 
Day 
Dose 
Fed/Fasted* 
TBAJ-876 
Groups 1 & 2: Day 6 - 13 
TBAJ-876 oral suspension: 200 mg 
dose 
Fed 
Groups 1 & 2: Day 14 - 19 
TBAJ-876 oral suspension: 165 mg 
dose 
Fed 
Group 1: Day 20 - 21 
TBAJ-876 oral suspension: 200 mg 
dose  
Fasted 
Group 2: Day 20 
TBAJ-876 oral suspension: 200 mg 
dose  
Fasted 
Group 1: Day 22 - 24 
TBAJ-876 oral suspension: 150 mg 
dose 
Fed 
Group 2: Day 21 - 24 
TBAJ-876 oral suspension: 150 mg 
dose 
Fed 
Midazolam (Group 1) 
Day 1 and Day 20 
Midazolam oral syrup: 2 mg  
Fasted 
Digoxin (Group 1) 
Day 2 and Day 21 
Digoxin tablet: 0.25 mg 
Fasted 
TLD (fixed dose combination of dolutegravir 50 mg + tenofovir disoproxil fumarate 300 
mg + Lamivudine 300 mg) (Group 2) 
Day 1 and Day 20 
TLD  
Fasted 
*Refer to Section 6.3 for details on the intake of meals and beverages 
 
Group 1:  
Subjects will be housed in the clinic from at least 24 hours prior to dosing (from Day -1) and 
remain in the research center until completion of the procedures on Day 25 and will receive 
a phone call on Day 32 to check for AEs and concomitant medications. 
 
• 
Subjects will check-in to the clinic following a 21-day screening period.   
• 
On Day 1, subjects will receive a single dose of Midazolam (2 mg syrup) under fasted 
conditions.  
• 
On Day 2, subjects will receive a single dose of Digoxin (0.25 mg) under fasted 
conditions.   
• 
On Day 6 - 13, subjects will receive single daily doses of 200 mg TBAJ-876 under fed 
conditions.  
• 
On Day 14 - 19, subjects will receive single daily doses of 165 mg TBAJ-876 under fed 
conditions    
• 
On Day 20, subjects will receive a single dose of Midazolam + a single dose of 200 mg 
TBAJ-876 under fasted conditions.  
• 
On Day 21, subjects will receive a single dose of Digoxin + a single dose of TBAJ-876 
200 mg under fasted conditions.  


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• 
On Day 22 – 24, subjects will receive a single daily dose of 150 mg TBAJ-876 under 
Fed conditions and will be discharged from the clinic on Day 25.  
 
Group 2: 
To be conducted based on the Group 1 results. Subjects will be housed in the clinic from 
at least 24 hours prior to dosing (Day -1) and remain in the research center until completion 
of the procedures on Day 25 and receive a follow-up phone call on Day 32 to check for AEs 
and concomitant medications. 
 
• 
Subjects will check into the clinic on Day -1 following a 21-day screening period.    
• 
On Day 1, subjects will receive a single dose of a Fixed Dose combination (TLD) of: 
Dolutegravir (DTG 50 mg) + Tenofovir disoproxil fumarate (TDF 300 mg) + 
Lamivudine (3TC 300 mg) under fasted conditions.  
• 
On Day 6 – 13, subjects will receive a single daily dose of 200 mg TBAJ-876 under fed 
conditions.  
• 
On Day 14 – 19, subjects will receive a single daily dose of 165 mg TBAJ-876 under 
fed conditions.  
• 
On Day 20, subjects will receive a single dose of the fixed dose combination (TLD) of 
DTG/TDF/3TC plus a single dose of 200 mg TBAJ-876 under fasted conditions. 
• 
On Day 21 – 24, subjects will receive a single daily dose of 150 mg TBAJ-876 under 
fed conditions. 
• 
On Day 25, subjects will be discharged from the clinic following completion of all 
procedures. 
5 
Study Population 
Healthy adult male and female subjects, ages 18 – 55 inclusive. Subjects must meet all inclusion 
and no exclusion criteria within the screening period 
Group 1:  Plan to enroll: 
Twenty- eight (28) subjects. 
Group 2:   Plan to enroll: 
Sixteen (16) subjects. 
5.1 
Inclusion Criteria 
All subjects must satisfy the following criteria to be considered for study participation: 
1. Understands study procedures and voluntarily provides written informed consent prior to the 
start of any study-specific procedures. 
2. Is a healthy adult male or female, 18 to 55 years of age (inclusive) at the time of screening.  
3. Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 
kg at the time of screening and check-in. 
4. Is medically healthy with no clinically significant screening results (e.g., laboratory profiles 
normal or up to Grade 1 per Division of Microbiology and Infectious Diseases (DMID) Toxicity 
Tables), as deemed by the Investigator. Note: Lab results within the testing facility’s normal 


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range will not be considered AEs when referenced to the DMID assessment/grading scale. If 
exclusionary lab criteria are met, values may be confirmed by repeat evaluation. 
5. Has not used tobacco- or nicotine-containing products (including smoking cessation 
products), for a minimum of 6 months before dosing.  
6. If female of non-childbearing potential, she has undergone one of the following sterilization 
procedures at least 6 months before dosing: 
• 
Hysteroscopic sterilization. 
• 
Bilateral tubal ligation or bilateral salpingectomy. 
• 
Hysterectomy; or 
• 
Bilateral oophorectomy. 
• 
Or is postmenopausal with amenorrhea for at least 1 year before the first dose with 
serum FSH levels consistent with postmenopausal status (i.e., greater than 40 
mIU/mL) at screening.  
7. If female of childbearing potential, must be using effective birth control methods, as defined 
below and is willing to continue practicing birth control methods and not planning to conceive 
throughout treatment and until 17 weeks after the last dose of TBAJ-876.  The following are 
allowed birth control methods for this study: 
• 
Double barrier method (e.g., diaphragm with spermicide; condoms with 
spermicide). 
• 
Intrauterine device. 
• 
Abstinence (and must agree to use a double barrier method if they become 
sexually active during the study).Vasectomized partner (at least 6 months before 
dosing). 
• 
Non-surgical permanent sterilization (e.g., Essure® procedure) at least 3 months 
before dosing. 
• 
Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive 
months before study dosing. 
8. If a non-vasectomized male (or male vasectomized less than 6 months prior to study start) he 
must agree to the following during study participation and for 90 days after the last follow-up 
visit (or until at least 90 days after the date of early withdrawal): 
• 
Use a condom with spermicide while engaging in sexual activity or be sexually 
abstinent; and  
• 
Not donate sperm during this time.  
In the event the sexual partner is surgically sterile or postmenopausal, use of a 
condom with spermicide is not necessary. None of the birth control restrictions listed 
above are required for vasectomized males whose procedure was performed more 
than 120 days before study start. 
9. Is willing to answer inclusion and exclusion criteria questionnaire at check-in. 
10. Is able to comply with the protocol and the assessments therein, including all restrictions. 
11. Is willing and able to remain in the study unit for the entire duration of the assigned 
confinement period and return for outpatient visits. 


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12. Is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe 
required. 
5.2 Exclusion Criteria 
Subjects will be excluded from the study if there is evidence of any of the following criteria at 
screening or check-in, as appropriate.  
1. History or presence of significant cardiovascular abnormalities, Heart Murmur, pulmonary, 
hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, 
neurological, or psychiatric disease as determined by the Investigator to be clinically relevant.  
2. Any musculoskeletal abnormality (severe tenderness with marked impairment of activity) or 
musculoskeletal toxicity (frank necrosis).  
3. History of any illness that, in the opinion of the Investigator, might confound the results of the 
study or poses an additional risk to the participant by their participation in the study. 
4. Surgery within the past 90 days prior to dosing or other previous surgery as determined by 
the Investigator to be clinically relevant.  
5. History or presence of alcoholism or drug abuse within the past 2 years as determined by the 
Investigator to be clinically relevant. 
6. Female subjects who are pregnant or lactating. 
7. Positive results for the urine drug/alcohol breath screen at screening or check-in. 
8. Positive urine cotinine at screening or check-in. 
9. Subjects with the following laboratory abnormalities at screening or Day -1: 
a. ALT or AST >1.0 times upper limit of normal (ULN) 
b. Creatinine grade 2 or greater (>1.5 times ULN) 
c. Total lipase or amylase >1.0 times ULN 
d. Total bilirubin grade 1 or greater (>1.0 times ULN) 
e. CPK >1.25 times ULN 
If exclusionary lab criteria are met, values may be confirmed by repeat evaluation.  
10. Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B Surface 
Antigen (HBsAg), or Hepatitis C antibodies (HCV). Note: Subjects with positive HCV 
antibody but negative polymerase reaction (PCR) can be allowed in the study. 
11. Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results within 6 days 
prior to Day 1. 
12. Seated or supine blood pressure is less than 90/40 mmHg or greater than 150/90 mmHg at 
screening, Day -1 (check-in), or pre-dose. Out of range vital signs may be repeated twice for 
confirmation.   
Out of range values will not be considered AEs if the repeat assessment is in range.  
13.  Heart rate is lower than 60 beats per minute (bpm) or higher than 100 bpm at screening, Day 
-1 (check-in), or pre-dose. Out of range vital signs may be repeated once for confirmation. Out 
of range values will not be considered AEs if the repeat assessment is in range.  
14. Any clinically significant electrocardiogram abnormality at Screening (as deemed by decision 
of the Investigator and the Sponsor’s Medical Monitor).  
NOTE: The following can be considered not clinically significant without consulting the 
Sponsor’s Medical Monitor:  


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a.  Right or left axis deviation  
b.  Incomplete right bundle branch block  
c.  Isolated left anterior fascicular block (left anterior hemiblock) in younger athletic subjects  
15. QTcF interval >450 ms for males or >470 ms for females at screening, Day -1, or Day 2 (pre-
dose), or history of prolonged QT syndrome. PR interval < 200 ms at screening, Day -1 or Day 
2 pre-dose. Out of range values may be repeated twice for confirmation. The average QTcF 
and PR intervals of the three ECG recordings will be used to determine qualification.  
16. Family history of Long-QT Syndrome or sudden death without a preceding diagnosis of a 
condition that could be causative of sudden death (such as known coronary artery disease, 
congestive heart failure or terminal cancer).  
17. Use of any prescription medication within 14 days prior to dosing.  
18. Use of any over the counter (OTC) medication, including herbal products and vitamins, within 
the 7 days prior to dosing, except acetaminophen. Up to 3 grams per day of acetaminophen 
is allowed at the discretion of the Investigator prior to dosing.  
19. Use of any drugs or substances known to be significant inhibitors of Cytochrome P450 (CYP) 
enzymes and/or significant inhibitors or substrates of P-glycoprotein (P-gp) and/or Organic 
anion transporting polypeptides (OATP) within 14 days prior to the first dose of study drug.  
20. Use of any drugs or substances known to be inducers of CYP enzymes and/or P-gp, including 
St. John’s Wort, within 30 days prior to the first dose of study drug.  
21. Participation in another clinical study within 30 days prior to dosing.  
22. Has been on a significantly abnormal diet during the 4 weeks preceding the first dose of study 
medication.  
23. Unwilling to remove any artificial nails (e.g., acrylic, gel) or fingernail polish and not use such 
products for the duration of the study.  
24. Is lactose intolerant 
25. Current diagnosis of bulimia or anorexia nervosa 
26. History or presence of allergic, or adverse response to midazolam, digoxin, dolutegravir, 
tenofovir, lamivudine or any related drugs. 
5.3 Restrictions 
Subjects must not donate blood from 56 days or plasma from 7 days prior to the first dose of study 
medication until the last follow-up visit (Day 32 phone call) or early withdrawal visit is completed. 
It is recommended that blood/plasma donations not be made for at least 30 days after the last 
follow-up visit or early withdrawal visit. 
Subjects must not use tobacco- or nicotine-containing products (including smoking cessation 
products) from 6 months prior to the first dose of study medication until the last follow-up visit or 
early withdrawal visit is completed. 
Subjects must not consume alcohol from 72 hours prior to the first dose of study medication until 
the last follow-up visit or early withdrawal visit is completed. However, allowance for an isolated 
single incidental consumption may be evaluated and approved by the study Investigator based 
on the potential for interaction with the study drug. 


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Subjects must not consume beverages or foods that contain grapefruit or Mandarin oranges from 
10 days before the first dose of study medication, or poppy seeds, broccoli, Brussels sprouts, 
pomegranate, star fruit, cherries, char-grilled meat, or caffeine/xanthine from 24 hours before the 
first dose of study medication, until the last follow-up visit, or early withdrawal visit is completed. 
Subjects will be instructed not to consume any of the above products; however, allowance for an 
isolated single incidental consumption may be evaluated and approved by the study Investigator 
based on the potential for interaction with the study drug. 
Subjects must not engage in strenuous exercise from 48 hours prior to the first dose of study 
medication until after discharge from the clinic. For follow-up visits, subjects must not engage in 
strenuous exercise during the 3 days prior to the visit. Any report of exercise will be documented 
and recoded as a protocol deviation. Subjects may continue in the study at the discretion of the 
study Investigator.  
5.4 Stopping Rules 
If any of the stopping rules are met, dosing must be stopped to allow review of the data by the 
Sponsor and the Investigator. 
Rules for stopping dosing in all patients include the following:  
• 
One subject experiences one or more drug-related serious adverse events (SAEs).   
• 
Two or more subjects experience Grade 3 or 4 (per DMID) myalgia in combination with 
increase of CPK (at least 3 times the upper limit of the normal range [ULN] confirmed at 
48 hours). 
• 
Two or more subjects have a QTcF ≥ 500 ms with an increase from baseline > 60 ms. 
• 
Two or more subjects experience confirmed Grade 3 or 4 AEs (per DMID) in any one of 
the following laboratory parameters: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), amylase, or lipase. 
5.5 Discontinuation from Treatment/Study 
The following may result in the discontinuation of study treatment: 
• 
Pregnancy 
• 
Withdrawal of informed consent 
• 
Investigator considers it for safety reasons in the best interest of the participant that he/she 
be discontinued 
• 
Adverse event resulting in death 
• 
Lost to follow-up 
• 
Termination of the study by the sponsor 
A subject may withdraw from the study at any time at his/her request (withdrawal of consent) or 
may be withdrawn at any time at the discretion of the Investigator for safety, behavioural, 
compliance or administrative issues.  All subjects withdrawn from study having received at least 
one dose of IMP will be requested to return for an early withdrawal visit and applicable safety 
Follow Up visits, as per Flow Chart (Section 1.2). 
Subjects who withdraw from the study after having received study drug can be replaced after 
agreement between the Sponsor and investigator. 


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5.6 Trial Duration 
Group 1 and Group 2 
The planned length of participation in the study for each subject is approximately 34 Days from 
Check-in on Day -1 through completion of the clinical procedures on Day 25 and a follow-up 
phone call on Day 32. 
6 
Treatment 
6.1 Administration of TBAJ-876 Oral Suspension  
Note: Detailed instructions for preparing and dispensing TBAJ-876 Oral Suspension will be 
provided in a separate pharmacy manual. Any instructions in the pharmacy manual shall 
supersede those presented in this protocol. 
TBAJ-876 Oral Suspension will be transferred and stored in Pyrex glass reagent bottles with a 
polypropylene (PP) screw cap without a liner. These bottles will be used for mixing, sampling, and 
storage prior to administration. 
The required doses of the drug product will be dispensed using commercially available oral 
syringes of suitable capacity. The suspension will be dispensed just prior to dosing and not stored 
in the oral syringes. 
Refer to Appendix 2: Description and Composition of Investigational Medicinal Product (IMP) for 
details. 
Each dose of TBAJ-876 Oral Suspension will be administered orally followed by approximately 
240 mL of room temperature water. A mouth check will be performed immediately after dose to 
ensure that the medication has been appropriately swallowed. 
Subjects will remain seated, except as otherwise required for study procedures or personal 
needs, for the first 4 hours after dosing. Should the need to move about occur during the first 4 
hours after dosing on these days, subjects may be escorted to such procedures or activities by 
research personnel as deemed medically necessary. Subjects will not be allowed to lie down, 
except as directed by clinical staff secondary to AEs, for the first 4 hours after dosing. 
6.2 Administration of the Interaction Products 
When the TBAJ-876 is administered with the interaction products the interaction product will be 
administered first followed by TBAJ-876. The time of interaction product dosing will be 
considered ‘0’ hour. The elapsed time from start to finish for administration of both 
medications should not exceed 5 minutes. The time of dosing for each of the medications 
must be recorded on the CRF.  
Each dose of the interaction products will be orally administered in accordance with individual 
package insert provided with the drug.  
The subjects will remain seated, except as otherwise required for study procedures or personal 
needs, for the first 4 hours after dosing. Should the need to move about occur during the first 4 


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Protocol Version: V1.0/ 20 May22 
 
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hours after each dose, subjects may be escorted to such procedures or activities by research 
personnel as deemed medically necessary. Subjects will not be allowed to lie down, except as 
directed by clinical staff secondary to AEs, for the first 4 hours after dosing. 
6.3 Fasting/Meals/Beverages 
Optional meals (lunch, snack, and dinner) may be served the day of check-in and Day -1.  
All subjects will then be required to fast for at least 10 hours before dosing on Days 1, 2, 20 and, 
in Group 1, 21. The subjects will fast for 4 hours after dosing.  
Subjects during the Fed period will receive the required FDA standard high-fat, high-calorie 
breakfast that has to begin 30 minutes before the scheduled administration of the dose and end 
(last bite taken) within 5-10 minutes before dosing. The subjects will fast for 4 hours thereafter. 
The following high-fat (approximately 50% of total caloric content of the meal), high-calorie 
(approximately 1000 calories) breakfast (details below) should be ingested within 30 minutes or 
less. 
2 eggs fried in butter 
2 strips of bacon  
2 slices of toast with butter 
4 ounces of hash brown potatoes 
8 ounces of whole milk 
 
This meal contains approximately 150 protein calories, 250 carbohydrate calories, and 500-600 
fat calories. An equivalent meal may be substituted with documentation of the menu and caloric 
contents. 
Standard meals will be provided at approximately 4 and 10 hours after drug administration and at 
appropriate times thereafter. 
Beverages 
Each dose of TBAJ-876 Oral Suspension and Interaction Product will be administered orally 
followed by approximately 240 mL of room temperature water.  
Except for the room temperature water provided with the study treatment, no water may be 
consumed for 1 hour prior to each dose through 1 hour after each dose. At other times, subjects 
will be encouraged to drink water ad libitum. 
6.4 Subject Compliance 
The date and time of each dose administered in the clinic will be recorded in the source 
documents. The dose of study treatment and study participant identification will be confirmed at 
the time of dosing by a member of the study site staff other than the person administering the 
study treatment. 
6.5 Method of Treatment Assignment 
Subjects will be randomized sequentially.  All subjects will receive active drug. 


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6.6 Handling, Storage and Accountability  
The investigator or designee must confirm appropriate temperature conditions as per details on 
IMP labelling, have been maintained during transit for all study treatment received and any 
discrepancies are reported and resolved before use of the study treatment. 
Only subjects enrolled in the study may receive study treatment and only authorized site staff may 
supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labelled storage conditions with access limited to the investigator and authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is responsible 
for study treatment accountability, reconciliation, and record maintenance (i.e., receipt, 
reconciliation, and final disposition records).  Upon completion or termination of the study, all 
unused and/or partially used IMPs must either be returned to Sponsor (or designated vendor) 
who will arrange for destruction or destroyed at site as agreed by Sponsor after final accountability 
has been confirmed. 
The Investigator/designee will immediately inform the Sponsor of any quality issues arising with 
respect to the study medication. The Sponsor will take whatever action is required should such a 
situation arise. 
Further guidance and information for the handling, storage, accountability, and final disposition of 
unused study treatment are provided in the Drug Preparation Protocol and/or Pharmacy Manual. 
7 
Study Procedures 
7.1 Screening  
The informed consent documents (ICDs) will be discussed with each potential participant, and 
each individual will sign an ICD for the study before any study-specific procedures being 
performed. 
Each potential study participant will have the following assessments by the Investigator or 
designee within 21 days before study start:   
• 
Demographic data, including sex, age, race, ethnicity, body weight (kg), height (cm), BMI 
(kg/m2), and smoking habits.  
• 
Medical history 
• 
Physical examination 
• 
Vital signs (blood pressure, pulse rate, respiration rate, temperature, and pulse oximetry) 
• 
12-lead safety ECG 
• 
Clinical laboratory tests (hematology, coagulation, chemistry, and urinalysis) 
• 
Serology tests for HIV, hepatitis B and C 
• 
Urine test for drugs of abuse and cotinine 
• 
Serum pregnancy (all female subjects) 
• 
FSH test (post-menopausal females)   
• 
Concomitant medication review 
 


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Protocol Name/Number: TBAJ-876-CL002 
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Only medically healthy subjects with clinically acceptable laboratory profiles and ECGs within the 
defined parameters who fulfil all other inclusion criteria and meet none of the exclusion criteria 
outlined in the previous sections will be enrolled in the study. 
Subjects will be assigned numbers in an ascending order, based on successful completion of the 
screening process. 
7.2 Check-in Procedures 
Subjects will check into the clinic on Day -1. 
At check-in, all subjects will be evaluated to confirm they continue to meet all the inclusion criteria 
(Section 5.1) and none of the exclusion criteria (Section 5.2).  
Subjects will undergo the following assessments during the confinement period prior to dosing: 
• 
Physical examinations 
• 
Weight 
• 
Vital signs (blood pressure, pulse rate, respiration rate, temperature, and pulse oximetry) 
• 
12-lead ECG 
• 
Clinical laboratory tests (hematology, coagulation, chemistry, and urinalysis) – myoglobin 
will be collected but results will not be required for dose qualification. 
• 
Urine drug, alcohol, and cotinine screens – results must be negative for the subject to 
continue study participation 
• 
Serum pregnancy test (all female subjects) – results must be negative for the subject to 
continue study participation 
• 
Concomitant medication review 
7.3 Subject Assignment 
Subjects will receive a 4-digit number on Day 1 before IMP drug administration. The assignment 
of a number and code for participant identification is based on the obligation for anonymity. 
7.4 Confinement 
Group 1 and Group 2: Subjects will be admitted to the research center on Day -1 and remain 
in the research center until completion of procedures on Day 25. 
7.5 Blood Sampling, Processing and Shipment 
Blood samples will be collected as detailed in the Appendix 1. 
Refer to the Schedule of Assessments & Procedures (Group 1: Section 1.2.1 or Group 2: 
Section 1.2.2) for specific blood collection time points. The PI, in conjunction with the Sponsor, 
may collect additional blood, if necessary, for repeat laboratory or safety evaluations including AE 
follow-up.  
Two aliquots of each blood sample will be prepared. One set aliquot of the plasma samples will 
be sent to the bioanalytical lab.  After receiving the first set of plasma samples (back-up samples) 
will also be sent to the bioanalytical lab. 


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Group 1 
A total of 144 mL (12 x 4 mL samples + 48 x 2 mL samples) will be collected from each 
participant for PK analysis. Approximately 141.1 mL of blood will be collected for the clinical 
laboratory evaluations and coagulation testing. The total volume of blood collected from each 
participant in Group 1 will not exceed approximately 285.1 mL (Table 5). 


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Table 5 
Total predicted Volume of Blood to be Collected for Testing: Group 1 
Reason for Collection 
Number of 
Samples 
Volume per 
Sample (mL) 
Total Volume 
(mL) 
Clinical labs at screening 
1 
19.5 
19.5 
Clinical labs during study 
(check-in and Days 2, 3, 7, 
20, 21, 22 and 25 or early 
withdrawal 
8
12.5 
100 
Coagulation 
8 
2.7 
21.6 
Pharmacokinetic analysis 
(TBAJ-876 Day 17) 
12 
4 
48 
Pharmacokinetic analysis 
(Midazolam Day 1 and Day 
20) 
22 
2 
44 
Pharmacokinetic analysis 
(Digoxin Day 2 and Day 21) 
26 
2 
52 
Total 
285.1 
Group 2 
A total of 172 mL (43 x 4 mL samples) will be collected from each participant for PK analysis. 
Approximately 100.7 mL of blood will be collected for the clinical laboratory evaluations 
and coagulation testing. The total volume of blood collected from each participant in Group 2 
will not exceed approximately 294.7 mL (Table 6). 


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Table 6 
Total predicted Volume of Blood to be Collected for Testing: Group 2 
Reason for Collection Group 2 
Number of 
Samples 
Volume per Sample 
(mL) 
Total Volume (mL) 
Clinical labs at screening 
1 
19.5 
19.5 
Clinical labs during study (check-in and 
Days 2, 7, 20, 21, 25 + early 
withdrawal 
6 
12.5 
75 
Coagulation 
6 
2.7 
16.2 
Pharmacokinetic analysis (TBAJ-876 
Day 17) 
12 
4 
48 
Pharmacokinetic analysis (TLD Day 1) 
17 
4 
68 
Pharmacokinetic analysis (TLD Day 
20) 
17 
4 
68 
Total 
294.7 
 Pharmacokinetic Sampling Time Windows 
Blood samples collected outside the time windows listed below will be considered deviations. 


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Table 7 
Acceptable Pharmacokinetic Sampling Time Windows 
Investigation 
and 
Examination 
Allowable Time Window 
 
Pre-dose 
0-24 hours 
>24 hours to 
Day 25 
Plasma sample 
collection for 
pharmacokinetic 
assessment 
Within 1 hour 
pre-dose 
 
+- 5 minutes 
+- 15 minutes 
7.6 Safety Monitoring and Procedures 
Refer to the Flow Chart in Section 1.2 for full details on the visit window periods. 
The following safety and tolerability variables will be collected at the time points described in the 
study flow chart and assessed for evaluation of the safety endpoints: 
 Adverse Events 
Subjects will be instructed to inform the study physician and/or research personnel of any Adverse 
Events (AE) that occur at any time during the study. Subjects will be monitored for AEs from the 
time of signing the ICD through the end-of-study visit.  
Refer to Section 8 for details regarding AE reporting. 
 Laboratory parameters 
Clinical laboratory evaluations will be performed at the times noted on the appropriate schedule 
of events (Section 1.2). A Clinical Laboratory Improvement Amendments (CLIA) certified 
laboratory will perform all clinical laboratory tests for this study. 
• 
Hematology: hemoglobin, hematocrit, , red blood cell (RBC) count, white blood cell count 
with differential, reticulocyte count, and platelet count. 
• 
Serum Chemistry: albumin, blood urea nitrogen (BUN), creatinine, creatine 
phosphokinase (CPK), direct, indirect, and total bilirubin, alkaline phosphatase (ALP), 
aspartate transaminase (AST), alanine transaminase (ALT), sodium (Na+), potassium 
(K+), chloride (Cl-), lactate dehydrogenase (LDH), calcium (Ca), uric acid, glucose, total 
protein, magnesium, and bicarbonate, lipase, and amylase. 
Note: If a subject experiences an increase in CPK Grade 2 (≥1.6 x ULN) the following 
tests should be performed: creatine phosphokinase of myocardial band (CPK-MB), 
trypsin like immunoreactivity, and cardiac troponin I. 
• 
Serology: hepatitis B surface antigen, hepatitis C antibody, and HIV 
• 
Coagulation: prothrombin time (PT2) and activated partial thromboplastin time (aPTT2). 
• 
Urinalysis - The following will be evaluated by an automated or manual urine “dipstick” 
method: pH, specific gravity, protein, glucose, ketones, bilirubin, creatinine, nitrite, sodium, 
urobilinogen, myoglobin, blood, leukocyte esterase, and urobilinogen. If protein, occult 
blood, nitrite, or leukocyte esterase values are out of range, a microscopic examination 


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will be performed. Myoglobin will be collected but results will not be required for dose 
qualification. 
• 
Urine Drug, Cotinine, and Alcohol Screens - Urine samples will be tested for drugs of 
abuse (amphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, opiates) 
cotinine, and alcohol. 
• 
Pregnancy test (all female subjects). 
• 
FSH (female subjects claiming post-menopausal status). 
 Vital Signs 
Vital signs (blood pressure, heart rate [pulse], temperature, respiration rate, and pulse oximetry) 
should be measured at screening, check-in, and Day -1. Vital sign measurements should be taken 
within 90 minutes prior to dosing and within 15 minutes of the defined time points in flowchart at 
study hours 0, 0.5, 1, 2, 6, and 12 on Days 1, 2, 6, 20, 21, and 24. Furthermore, vital signs 
should also be taken once daily on Day 7 through Day 20 (6 hours after Dosing) and Day 25 or 
early withdrawal (must be done within 15 minutes before review of medication and collection of 
adverse experiences)Both blood pressure and heart rate should be captured simultaneously. 
Blood pressure and heart rate should be measured after subjects are in supine position for at 
least 2 minutes and then again after standing for at least 1 minute (starting with 2 hours post 
dose), except when they are supine or semi-reclined because of study procedures and/or adverse 
events, or as deemed necessary by the Investigator. 
 Physical Examination 
Physical examinations including height and weight measurements and presence of heart murmur, 
will be conducted in the times noted on the appropriate events schedule (Section 1.2).  
 Electrocardiograms 
Group 1 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 3, 7, 20, 21, 22 and on Day 25 
or upon early withdrawal. The pre-dose ECG should be completed within 20 minutes prior to the 
pre-dose blood draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-
baseline QTcF >60 ms, after repeat testing, additional ECGs should be recorded until 
normalization or return to baseline. 
 
Group 2 
 
Single 12-lead safety ECGs will be printed and reviewed on-site by the Principal Investigator or 
designee. Single ECGs will be completed at screening, Day -1, 2, 7, 20, 21 and 25 or upon early 
withdrawal. The pre-dose ECG should be completed within 20 minutes prior to the pre-dose blood 
draw. If a participant experiences a post-dosing QTcF >500 ms or a change-from-baseline QTcF 
>60 ms, after repeat testing, additional ECGs should be recorded until normalization or return to 
baseline. 
 


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 Other Safety Measures 
Medical emergency personnel trained in advanced cardiac life support will be on site to monitor 
subjects during the confinement period in the research centre. Emergency medical equipment 
including but not limited to resuscitation equipment and pulse oximetry shall be maintained on 
site to administer appropriate medical care should it be required.  
Procedures will be completed as specified in this protocol unless contraindicated due to a reported 
AE. 
8 
Adverse Events 
Subjects will be monitored for any AEs from the signing of the consent form until the end-of-study 
visit. Adverse events for subjects who fail screening will be recorded in the source documents 
and maintained on site. The Investigator or a medically qualified designee will review each event. 
The Investigator or a Sub-Investigator will assess its relationship to the study drug. Each sign or 
symptom will be graded for severity, and the date and time of onset, cessation and resolution will 
be recorded. Treatment of any adverse reactions will be evaluated and managed by a physician, 
either at the study site or at a nearby hospital emergency room, as appropriate. All non-serious 
AEs will be reported on a regular basis or as specified by the Sponsor. 
8.1 Definitions 
 Adverse Event 
Any untoward medical occurrence in a clinical investigation participant, temporally associated with 
the use of a trial treatment whether or not considered related to trial treatment. An adverse event 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated with the use of a trial treatment, 
whether or not related to the trial treatment. 
 Serious Adverse Event 
Any untoward medical occurrence that at any dose: 
• 
Results in death 
• 
Is life threatening (any event in which the participant was at risk of death at the time of the 
event; it does not refer to an event, which hypothetically might have caused death if it were 
more severe) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization; In general, 
hospitalization signifies that the participant has been detained (usually involving at least 
an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfils any other serious criteria, the event is serious. When in doubt as 
to whether “hospitalization” occurred or was necessary, the AE should be considered 
serious. Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE 


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• 
Results in persistent or significant disability/incapacity; the term disability means a 
substantial disruption of a person’s ability to conduct normal life functions. This definition 
is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but do 
not constitute a substantial disruption 
• 
Is a congenital anomaly/birth defect; or 
• 
Is a medically important event. 
• 
Note:  Medical and scientific judgment should be exercised in deciding which is a medically 
important event that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or surgical 
intervention to prevent one of the outcomes listed above. Examples of such events are 
intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or the development of drug 
dependency or drug abuse.  A “suspected transmission of infectious agent by a medicinal 
product” is also considered a serious adverse event under the SAE criterion “Other 
medically important condition”.  
 
 Attribution/Causality 
An adverse reaction, the nature or severity of which is not consistent with the applicable product 
information (e.g., Investigator’s Brochure for an unapproved investigational product). 
• 
The investigator is obligated to assess the relationship between trial treatment and each 
occurrence of each AE/SAE. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to trial treatment administration 
will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure and/or Product Information, 
for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the Sponsor/designee. However, it is very 
important that the investigator always assess causality for every event before the initial 
transmission of the SAE data to the Sponsor/designee. 
• 
The investigator may change his/her opinion of causality considering follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
 


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Table 8 
Adverse Event Attribution/Causality Ratings 
Relatedness Rating 
Definition 
Not Related 
An adverse event, which is not related to the use of the drug. 
Unlikely 
An adverse event for which an alternative explanation is more 
likely, e.g., concomitant drug(s) or concomitant disease(s), and/or 
the relationship in time suggests that a causal relationship is 
unlikely. 
Possible 
An adverse event, which might be due to the use of the drug.  An 
alternative explanation, e.g., concomitant drug(s) or concomitant 
disease(s), is inconclusive.  The relationship in time is 
reasonable; therefore, the causal relationship cannot be 
excluded. 
Probable 
An adverse event, which might be due to the use of the drug.  
The relationship in time is suggestive, e.g., confirmed by 
dechallenge.  An alternative explanation is less likely, e.g., 
concomitant drug(s) or concomitant disease(s). 
Certain 
An adverse event, which is listed as a possible adverse reaction 
and cannot be reasonably explained by an alternative 
explanation, e.g., concomitant drug(s) or concomitant disease(s).   
 


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Table 9 
Definitions for Adverse Event Severity Gradings 
Grade 
Severity Rating 
Definition 
GRADE 1 
Mild 
Transient or mild discomfort (< 48 hours); no medical 
intervention/therapy required. 
GRADE 2 
Moderate 
Mild to moderate limitation in activity - some assistance 
may be needed; no or minimal medical 
intervention/therapy required. 
GRADE 3 
Severe 
Marked limitation in activity, some assistance usually 
required; medical intervention/therapy required, 
hospitalizations possible. 
GRADE 4 
Potentially Life-
Threatening 
Extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy 
required, hospitalization or hospice care probable. 
 
See Appendix 3 for full DMID Toxicity Scale. The above ratings should be used to estimate the 
grade for abnormalities NOT found elsewhere in the Toxicity Tables.  
Lab results within the testing facility’s normal range will not be considered AEs when referenced 
to the FDA assessment/grading scale (Appendix 3, A). 
 
8.2 Reporting 
 Adverse Event 
Adverse Events will be collected by the Investigator or qualified designee(s) from the time a 
subject signs the Informed Consent Form through the end-of-study. Any AE (serious or non-
serious) observed by the Investigator (or a suitably medically qualified designee) or reported by 
the subject will be recorded on the Adverse Event Case Report Form (CRF). The Investigator 
will review each AE and assess its relationship to drug treatment based on all available 
information at the time of the completion of the CRF. The following information will be recorded 
for each Adverse Event reported: 
• 
Diagnosis of the AE, if possible. In the case where an overall diagnosis cannot be made, 
each specific sign and/or symptom will be recorded as individual AEs 
• 
Date of onset 
• 
Stop date (with duration, if applicable) 
• 
Severity  
• 
Action taken with IMP 
• 
Other action taken 
• 
Outcome 
• 
Relationship to IMP 


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•
Occurrence
•
Seriousness
8.3 Serious Adverse Event Reporting 
The Investigator or designee will notify the appropriate Sponsor contact immediately after the 
SAE detection, observation, or report of occurrence (regardless of the relationship to test article). 
The Sponsor contact information for SAE reporting is provided below: 
TB Alliance Pharmacovigilance 
Email: AE_inbox@tballiance.org 
Questions related to SAE case processing may also be sent to the above-mentioned email 
address.  If there is ever an email failure upon trying to report an SAE, please call Dr. Lombardi 
at 1-917-601-0024 and he will notify the Safety team at TB Alliance. 
Medical questions relative to AEs or SAEs can be directed to: 
Antonio (Tony) Lombardi, MD 
Global Alliance for TB Drug Development 
40 Wall Street, 24th Floor 
New York, NY  10005, United States of America 
Mobile: +1 917.601.0024 
Email: Antonio.Lombardi-Consultant@tballiance.org 
These SAE reports must contain the following information: 
•
Study name/number
•
Study drug
•
Investigator details (name, phone, fax, e-mail)
•
Subject number
•
Subject demographics
•
Clinical event:
o
Description
o
Date of onset
o
Treatment (drug, dose, dosage form)
o
Adverse event relationship to study drug
o
Action taken regarding study drug in direct relationship to the AE
•
If the AE was fatal or life-threatening
•
If applicable, cause of death (whether or not the death was related to study drug)
•
If applicable, autopsy findings (if available)
Any new SAE that occurs within one month after the study period and is considered to be possibly 
related to the Investigational Product (IP) should be recorded and reported immediately to the 
Sponsor.  
The person responsible for the study shall take care that the study has been carried out in 
accordance with pharmacovigilance local regulations. 


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All serious event reporting will adhere to U.S. Code of Federal Regulations (21 CFR Part 312.32) 
for Investigational New Drugs (IND) and 21 CFR 314.80 for marketed drugs (15-day alerts). The 
Institutional Review Board (IRB) will be notified of the alert reports per FDA regulations. 
All AEs, including SAEs, will be followed to resolution when possible. All AEs and treatment 
administered will be recorded on the CRF. 
The Sponsor will be responsible for reporting and processing any SAEs to the FDA or other 
applicable regulatory agency. 
8.4 Follow-up of Adverse Events 
All AEs will be followed until: 
• 
Satisfactory clinical resolution or stabilization; or 
• 
End of the follow-up period; and 
• 
All queries on these AEs have been resolved 
Certain long-term AEs cannot be followed until resolution within the setting of this protocol. In 
these cases, follow-up will be the responsibility of the treating physician. However, this will have 
to be agreed upon with the Sponsor Medical Monitor. 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by Sponsor or representative to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation with 
other health care professionals.  Investigator should contact Sponsor/designee to discuss 
appropriate medical follow-up if consultation required.  
If a participant dies during participation in the trial or during a recognized follow-up period, the 
investigator will provide Sponsor/representative with a copy of any post-mortem findings including 
histopathology. 
New or updated information on an SAE will be recorded in the originally completed CRF and 
submitted to Sponsor within 24 hours of the information becoming known per SAE reporting 
guidelines. 
8.5 Post-Trial Serious Adverse Events 
Any new SAEs reported by the subject to the Investigator that occur up to 30 days after last 
contact and are determined by the Principal Investigator to be possible, probable, or very likely 
related to the use of the IMP, will be reported to the Sponsor, IRB and FDA on an expedited basis 
as required in accordance with local requirements and International Council for Harmonisation 
(ICH) guidelines for GCP. 
8.6 Clinical Laboratory Adverse Events 
Changes in the results of the Clinical Laboratory assessment results which the Investigator feels 
are clinically significant will be reported as AEs. It is the Investigators’ responsibility to review the 
results of all laboratory tests as they become available. This review must be documented by the 


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Investigators’ dated signature on the laboratory report. For each abnormal laboratory test result, 
the Investigator needs to ascertain and document if this is a clinically significant change from 
baseline for that individual participant. This determination, however, does not necessarily need to 
be made the first time an abnormal value is observed. The Investigator may repeat the laboratory 
test or request additional tests to verify the results of the original laboratory tests. All laboratory 
changes greater than or equal to Grade 2 must be reported as an AE regardless of clinical 
significance.  
8.7 Drug Interaction 
If the investigator becomes aware that the subject has experienced a drug interaction which has 
resulted in an AE, it will be recorded as an AE. 
8.8 Pregnancy 
The Investigator will immediately notify the Sponsor of any pregnancy that is discovered during 
the clinical trial. Pregnancy forms will be completed for all pregnancies reported during the study 
or in the 30 days after completion of the IMP. In addition, the Investigator will report to the Sponsor 
follow up information regarding the outcome of the pregnancy, including perinatal and neonatal 
outcome. Infants should be followed for 6 months.   
If pregnancy is suspected while the subject is receiving IMP, the IMP will be withheld immediately 
until the result of the pregnancy test is known. If pregnancy is confirmed, the IMP will be 
permanently discontinued in an appropriate manner and the subject withdrawn from the trial. 
Protocol-required procedures for trial discontinuation and follow up will be performed unless 
contraindicated by the pregnancy. 
If the Investigator becomes aware the female partner of a male subject becomes pregnant during 
the study or in the 30 days after the completion of IMP, consent will be requested from the female 
partner for collection of information on her pregnancy history and for information on the current 
pregnancy and birth. 
8.9 Monitoring and Safety for Specific Toxicities 
Monitoring for specific toxicities is based upon target organs as defined in preclinical toxicity 
studies Investigator’s Brochure.  
 
Considering the safety findings in the toxicology studies regarding observed myocardial, skeletal 
muscle and minimal and mild liver injury, extensive monitoring with emphasis on cardiovascular 
monitoring as well as monitoring to evaluate potential hepatocellular and skeletal muscle injury 
will be performed. 
 
AEs still ongoing at the end of treatment in the study will be followed until satisfactory clinical 
resolution or stabilization or until the follow-up period and until all queries on those AEs have been 
resolved.  Grade 3 and Grade 4 abnormalities and laboratory abnormalities considered clinically 
significant should be followed until satisfactory resolution or stabilization.  
 
Note: For Grade 3 or 4 laboratory toxicities, subjects should have a confirmatory measurement 
within 48 hours where possible.  The recommendations for managing subjects below assume 
the laboratory abnormalities of concern have been confirmed. 


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If any of the following events occurs, the investigator should contact the Sponsor Medical 
Monitor to review: 
• 
Grade 3 or 4 myalgia 
• 
QTcF ≥ 500 ms with an increase from baseline > 60 ms (based on the mean of the 
replicate ECGs collected from the initial 12 lead ECG recording) confirmed within 30 
minutes if subject is symptomatic, and as soon as possible for asymptomatic subjects. 
• 
Grade 3 or Grade 4 adverse events in any one of the following laboratory parameters: 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline 
Phosphatase, total amylase or lipase confirmed within 48 hours. 
9 
General Principles 
9.1 Basic Principles 
This research will be carried out in accordance with the protocol, the ICH, Guideline for Good 
Clinical Practice: Consolidated Guidance (E6), and applicable regulatory requirements(s) 
including clinical research guidelines established by the Basic Principles defined in the U.S. 
21 CFR Parts 50, 56, and 312 and the principles enunciated in the Declaration of Helsinki (revised 
version Fortaleza 2013). 
9.2 Institutional Review Board 
This protocol will be reviewed by an appropriate IRB and study enrolment will not commence until 
the Board has approved the protocol or a modification thereof. The Board is constituted and 
operates in accordance with the principles and requirements described in 21 CFR Part 56. 
9.3 Informed Consent 
Written informed consent will be obtained from each subject prior to performing any baseline 
study-specific evaluations. The ICD is prepared by the Investigator or designee, subject to review 
and approval by the Sponsor, and forwarded to a qualified IRB for final review and approval. The 
IRB-approved document must contain, at minimum, the eight basic elements of informed consent. 
Only the most recently IRB-approved ICD must be used to consent prospective study subjects. 
One copy of the signed and dated ICD will be given to the subject and the original retained by the 
Investigator/site. 
9.4 Indications for Subject Withdrawal 
Subjects will be free to withdraw at any time for any reason, or they may be withdrawn, if 
necessary, to protect their health and safety or the integrity of the study data.  
Subjects who discontinue may be replaced at the Principal Investigator and Sponsor’s discretion. 
Subjects who have a positive urine drug, alcohol, or cotinine screen result will be evaluated on a 
case-by-case basis and the Principal Investigator and Sponsor will decide whether the subject 
will continue in the study or will be withdrawn. 


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The final report will include reasons for withdrawals. In the event of an early termination, subjects 
will undergo the procedures described in Section 5.5. 
Subjects who experience emesis may be replaced if the emesis could potentially impact drug 
absorption and therefore the PK data. Cases of emesis will be evaluated by the Sponsor and 
Principal Investigator to determine if subject replacement is needed. 
9.5 Termination of Study 
The Principal Investigator reserves the right to terminate the study in the interest of subject safety 
and welfare. The Sponsor reserves the right to terminate the study at any time for administrative 
reasons. 
9.6 Documentation 
All documents pertaining to the study, including a copy of the approved protocol, copy of the ICD 
and Health Insurance Portability and Accountability Act (HIPAA) documents, completed CRFs 
(where applicable), drug accountability and retention records, and other study related documents 
will be retained in the permanent archives of the study site. These will be available for inspection 
at any time by the Sponsor or the FDA. Per 21 CFR 312, record retention for this study is required 
for a period of two years following the date on which this study agent is approved by the FDA for 
the marketing purposes that were the subject of this investigation; or, if no application is to be 
filed or if the application is not approved for such indication, until two years following the date on 
which the entire study is completed, terminated, or discontinued, and the FDA is notified. 
Subject records will be kept private except when ordered by law. The following individuals will 
have access to study subject records: Principal Investigator and designees, study Sponsor, 
monitors, and auditors, the FDA, other government offices, and the IRB. 
9.7 Trial Monitoring 
Sponsor personnel (or designees) will be responsible for monitoring the study to ensure 
compliance with the protocol and GCP. Compliance may be verified by one or more of the 
following methods: on-site visits, frequent communication with the Investigator, and/or review of 
CRFs and source documents. The Investigator agrees to permit such monitoring as well as audits 
or reviews by regulatory authorities and the IRB. 
9.8 Reimbursement, Indemnity, and Insurance 
Reimbursement, indemnity, and insurance shall be addressed in a separate agreement on 
terms agreed upon by the parties. 
10 Statistical Analysis 
Statistical analyses will be performed using appropriate software, e.g. Phoenix™ WinNonlin® 
(Version 8.1 or higher, Pharsight Corporation) and SAS® (Version 9.4 or higher, SAS Institute 
Inc.). Pharmacokinetic parameters will be summarized using descriptive statistics. 


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All statistical reports must clearly indicate the group for the which the results are being 
summarised with a mention of the group in the report title. 
The safety and tolerability and Pharmacokinetic Statistical Analysis Plan (SAP) which will 
contain details of the analyses specified in this section, will be drafted, and signed off prior to 
data lock. The SAP will be written by TKL. 
10.1 Analysis Population 
Safety population will include data from all subjects who received at least one dose of IMP and/or 
1 dose of the interaction product. This population will be used to analyse the safety and tolerability 
endpoints. 
Pharmacokinetic (PK) population will include data from all subjects who received at least one 
dose of IMP and/or 1 dose of the interaction product and whose plasma concentration data is 
available. This population will be used for the presentation of plasma concentration results as well 
as PK analysis.  
10.2 Sample Size 
Sample sizes were determined with the objective of demonstrating no relevant impact of TBAJ-
876 on the probe substrates midazolam and digoxin or the components of the ARV combination 
TLD. Impact was measured by the geometric mean ratio (GMR), i.e., the ratio of the geometric 
mean AUC of the other drug with TBAJ-876 to the geometric mean AUC of the other drug without 
TBAJ-876, and similarly for Cmax. Absence of relevant impact would be concluded if a 90% 
confidence interval for the GMR falls within an acceptable target range. 
Per FDA’s Guidance for Industry “Clinical Drug Interaction Studies – Cytochrome P450 Enzyme- 
and Transporter-Mediated Drug Interactions”, the investigation of midazolam and digoxin is an 
Index Study, where the goal is to show no clinically significant interaction with a sensitive 
substrate. Therefore, the target range is the default no-effect range of 80% - 125%. 
The investigation of the ARVs is a Concomitant Use Study, where the target range is based on 
concentration-response or other available information about the substrate drug. DTG and TDF 
(active moiety TFV) are the two components of TLD where an interaction might be possible based 
on their involvement with CYP3A4 and/or P-gp. 
DTG is a CYP3A4 substrate, so induction of CYP3A4 may reduce DTG concentrations enough 
to impair efficacy. In the DTG label, the GMR for DTG was 0.65 when co-administered with 
fosamprenavir/ritonavir, and a doubling of the DTG dose was recommended. The GMR for DTG 
was 0.67 when co-administered with a multivitamin, and no change of the DTG dose was 
recommended. No dose adjustments were indicated due to interactions that increased DTG 
concentrations. Therefore, 67% seems to be a reasonable lower bound of the target range for 
DTG; a symmetric upper bound on the log scale would be 150%.  
TDF is a substrate for P-gp, so inhibition of TDF may increase TDF concentrations enough to 
compromise safety. In the TDF label, TFV increased 32% when TDF was co-administered with 
lopinavir/ritonavir, and monitoring for toxicity was recommended but no dose change. No dose 
adjustments were indicated due to interactions that decreased DTG concentrations. Therefore, 


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133% seems to be a reasonable upper bound of the target range for TFV; a symmetric lower 
bound on the log scale would be 75%.   
Sample sizes were determined assuming a two-period-fixed-sequence design, with the other drug 
given in Period 1 and the other drug plus TBAJ-876 in Period 2. Inference is then based on the 
within-subject differences log(AUCPeriod 2) – log(AUCPeriod 1) and similarly for Cmax. Given the target 
range and desired power, the necessary input for determining sample size is the standard 
deviation of such a difference, σAUC or σCmax.  
The desired power was taken to be 90%. Table 10 shows relevant standard deviations and implied 
sample sizes: 


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Table 10 Standard Deviations and Sample Sizes 
Drug 
Maximum of σAUC and σCmax. Sample Size for 90% Power 
Midazolam 
0.290 
20 
Digoxin 
0.325 
25 
Dolutegravir 
0.290 
8 
Tenofovir 
0.289 
13 
Source for midazolam and digoxin: 485516 (karger.com); standard 
deviations here are √2 x the values reported there. For dolutegravir and 
tenofovir, standard deviations were inferred from results reported in in the 
respective labels. 
For Group 1 of the study, the maximum of the required sample sizes for midazolam and digoxin 
was used, augmented by three additional subjects to allow for dropouts.  
Similarly for Group 2. 
10.3 Interim analysis 
No formal interim analyses are planned for this study. 
10.4 Demographics and Other Baseline Characteristics Analysis 
Demographics and other baseline characteristics will be summarized by safety population. 
Medical history and major protocol deviations will be listed. Any abnormal findings judged to be 
clinically significant will be documented as medical history or as a treatment-emergent adverse 
event, depending upon time of observation, as appropriate.  
Prior (prior to the start of treatment) medication use and concomitant (after the start of treatment) 
medication use will be summarized separately. If the end date of a prior medication occurs after 
treatment starts, then the medication will be reported in both the prior and concomitant tables and 
listings. These tables will present the number and percentage of subjects for each medication. 
10.5 Safety and Tolerability Analysis 
All safety analysis will be performed using the Safety analysis population and will be presented 
by group 
All safety and tolerability data collected in the study will be listed by participant. The continuous 
variables will be summarized using number of eligible subjects (N), mean, standard deviation, 
median, minimum, and maximum. Frequency counts and percentages will be reported for 
categorical data. 
Every cardiovascular safety incidence will be listed by timepoint with accompanying symptoms 
and with BP and HR measurements. 
Laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis) will be 
summarized using descriptive statistics. 


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ECG results will be classified as normal or abnormal and summarized using frequency counts by 
group and time point of collection. HR and blood pressure values and changes from pre-dose will 
be summarized using descriptive statistics for continuous variables. 
All adverse events will be coded using the latest version of Medical Dictionary for Regulatory 
Activities (MedDRA) at the time of finalisation of the Protocol and will be presented by Preferred 
Term within each MedDRA System Organ Class (SOC). Details related to pregnancy will only be 
listed.  
10.6 Pharmacokinetic analysis 
Plasma concentrations of TBAJ-876 and interaction products will be listed by participant and visit 
details as applicable by group. 
Summary statistics for analyte concentrations and the pharmacokinetic parameters, excluding 
Tmax, will be arithmetic mean, geometric mean, standard deviation (SD), geometric coefficient of 
variation (%CV), minimum (min), median, maximum (max) and number of subjects (n). Median, 
min, max, and n will be reported for Tmax.  The reports will be presented by group.  
Mean and individual concentrations (TBAJ-876, TBAJ-876 metabolites, and interaction products) 
will be plotted versus time. 
For pharmacokinetic and statistical calculations, all digits will be used for calculation. The final 
reportable results or data will be presented by rounding off to two decimal digits, (this applies to 
individual data and descriptive statistics but not to CV (%), which is rounded off to one decimal 
digit). 
Analysis for Group 1 will be conducted for induction potential of TBAJ-876 on the sensitive 
CYP3A4 substrate midazolam (M) and inhibition and induction potential of TBAJ-876 on the 
sensitive P-glycoprotein substrate Digoxin (D). 
TBAJ-876 will be considered a moderate inducer of either CYP3A4, if the GMR of midazolam 
AUC <0.50 when co-administered with TBAJ-876 versus alone, or P-glycoprotein, if the GMR of 
digoxin AUC <0.50 when co-administered with TBAJ-876 versus alone. TBAJ-876 will be 
considered a moderate inhibitor of P-glycoprotein if the GMR of digoxin AUC ≥2.0 when co-
administered with TBAJ-876 versus alone. These results will be used to decide whether to 
conduct of Group 2 of the study. 
Pharmacokinetic parameters for TBAJ-876 and interaction products will be calculated as 
defined in Table 11 below. 
Only subjects with measured concentrations adequate to determine PK parameters will be 
included in the PK parameter estimation. 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 66 of 84 
 
Table 11 Pharmacokinetic Parameters  
PK parameter 
Definition 
Cmax 
Maximum plasma concentration 
AUC0-24 
Area under the concentration curve from 0 to 24 h post-dose, calculated 
by trapezoidal integration (only for TBAJ-876 and its metabolites on Day 
17) 
SAUC 
Sum of AUC0-24 of TBAJ-876 and the M3 metabolite on Day 17. 
AUClast 
Area under the concentration curve from 0 to the last measurable 
concentration (only for interaction products) 
AUCinf 
Area under the concentration curve extrapolated to complete elimination 
(only for interaction products) 
Tmax 
Time of the maximum plasma concentration, given as the nominal time 
point 
Ctrough 
Trough concentrations (pre-dose or 24-hour) (only for TBAJ-876 and its 
metabolites on Day 17) 
Λz 
Elimination rate constant, calculated as the slope of log transformed 
concentration vs time during the elimination phase (only for interaction 
products) 
t½ 
Elimination half-life (only for interaction products) 
CL/F 
Apparent plasma drug clearance (only for interaction products) 
VZ/F 
Apparent volume of distribution (only for interaction products) 
 
To compare pharmacokinetic parameters of the interaction products with TBAJ-876 versus 
alone, analyses of variance (ANOVA) will be performed by the SAS Mixed Linear Models 
procedure. The model will include subject as a random effect and treatment (with TBAJ-876 
versus alone) as a fixed effect. Following log transformation, geometric least-squares mean 
values and 95% confidence intervals (CIs) will be tabulated for each pharmacokinetic 
parameter. GMRs and 95% CIs will be calculated for Cmax, AUCinf, and AUClast of interaction 
products, with TBAJ-876 versus alone.  
11 Facilities 
CLINICAL TRIAL SITE 
TKL Research, Inc. 
One Promenade Blvd. Suites 1101 & 1201 
Fair Lawn, New Jersey 07410 
Telephone: 201.587.0500 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
TMP-C-SOP01-B V1.0 30-JAN-2019 
CONFIDENTIAL 
Page 67 of 84
CLINICAL LABORATORIES 
Laboratory Corporation of America Holdings 
69 First Ave 
Raritan NJ 08869 
ANALYTICAL LABORATORIES 
TBAJ-876 Analysis 
Alliance Pharma, Inc 
Contact for Sample Shipment: Ruth Guan 
17 Lee Boulevard 
Malvern, PA 19355 
Phone: 610.296.3152 
Fax: 610.296.3153 
Email: rguan@alliancepharmaco.com 
samples@alliancepharmaco.com 
Web: www.alliancepharmaco.com 
Interaction Products Analysis 
Pyxant Labs 
Contact: Adam Winstrom 
4720 Forge Rd, Suite 108 
Colorado Springs, CO 80907 
Phone: 719.593.1165 ext. 42 
Fax: 719.593.1625 
Email: awinstrom@pyxant.com 
12 Drug Supplies 
Global Alliance for TB Drug Development will supply a sufficient quantity of the study drug, TBAJ-
876 tartrate for preparation of TBAJ-876 Oral Suspension. Study drug will be shipped to TKL 
Research, Inc. pursuant to site SOPs. Upon receipt of the study drug, the study drug will be 
inventoried and stored in an environmentally controlled and secure, limited access area. For oral 
suspension, the suspending vehicle Ora-Sweet® (or equivalent) and other supplies will be 
procured, inventoried, and stored appropriately by TKL Research, Inc. pursuant to site SOPs. 
The lot numbers of the study drug, vehicle, and other supplies along with the expiration dates 
(where available) will be recorded and copies of the Certificate of Analysis (where available) will 
be maintained on file. Records will be maintained of the receipt and dispensation of the drugs 
supplied. 
Samples will be collected from each batch of test product (TBAJ-876 Oral Suspension) and stored 
frozen until the clinical study report is issued. At the conclusion of the study, any unused study 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 68 of 84 
 
drug will be returned to the Sponsor or destroyed by the site pursuant to written authorization by 
the Sponsor and applicable federal and state regulations. 
TKL will procure the interaction products for Group 1: Midazolam syrup (2 mg) and Digoxin tablets 
(0.25 mg).  
For Group 2, the fixed dose combination of dolutegravir (50 mg) plus tenofovir disoproxil fumarate 
(300 mg) plus lamivudine (300 mg), may not be available in the United States.  TB Alliance will 
assist in procuring if needed.  
13 Administrative Issues 
The Investigator is referred to the Investigator Brochure, or information provided during the 
study initiation visit, information provided by the study monitor, and ICH Guidelines for Good 
Clinical Practice for information regarding the study drug, details, or general considerations to 
be followed during this study.   
14 References 
1.TBAJ-876 Investigator’s Brochure. Edition: Version 2.0, Dated 03 March 2021 
2. Package Insert: Sirturo. Janssen Therapeutics, September 2014. Available at: 
https:www.accessdata.fda.gov/drugsatfda_docs/label/2012/20484s000lbl.pdf 
3. Package Insert for Midazolam Hydrochloride Syrup 
4. Digoxin Package Circular 
5.  ACRIPTEGA (Fixed Dose Combination  Dolutegravir/Lamivudine/Tenofovir disoproxil 
fumarate) Clinical Professional information and Patient Information Leaflet   
6. Tenofovir, Lamivudine, and Dolutegravir (TLD) Transition: General Information for Clients, 
Counselors, and other Service Providers 
 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 69 of 84 
 
APPENDICES 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 70 of 84 
 
APPENDIX 1 PHARMACOKINETIC SAMPLE COLLECTION, PROCESSING, AND 
SHIPMENT INSTRUCTIONS 
Collection and Processing TBAJ-876 
A more detailed description of plasma sample preparation requirements may be provided by the 
analytical laboratory. If such a description is provided, the method of sample preparation 
provided by the laboratory shall supersede those provided in this protocol and appropriate 
documentation shall be placed in the Investigator Site File (ISF). 
Processing Instructions 
1 
Samples will be collected via direct venipuncture at the time points delineated in 
the appropriate Events Schedule (Section 1.2).  
2 
Blood will be drawn into pre-chilled 4 mL evacuated tubes containing K3-EDTA and 
immediately placed on wet ice and then processed to plasma within 60 minutes. 
3 
Samples will be centrifuged at 1500 g at approximately 4°C (± 10 degrees) for 
10 minutes. After centrifugation, two aliquots of plasma (the first containing at least 
0.5 mL and the second containing the remainder of the plasma) will be removed 
and placed in appropriately labeled 1 mL polypropylene vials. 
4 
The aliquots will be immediately placed on dry ice. Within 90 minutes of collection, 
the aliquots will be stored in a freezer set at -80°C ± 10°C and remain in the 
freezer until transferred for analysis. 
5 
Samples will be transferred at the agreed upon intervals. 
6 
The aliquots will be transferred on dry ice to the Alliance Pharma, Inc. bioanalytical 
laboratory for the determination of plasma concentrations of TBAJ-876 and its 
metabolites (M2 and M3) using a validated procedure at Alliance Pharma. 
7 
Blood sampling, plasma processing, and storage time will be documented in the 
study records. 
 
Labeling of aliquot tubes 
Labels will contain at least the following information: 
a) Study number 
b) Subject identification 
c) Period or dosing phase; sampling time (relative to dosing) 
d) Aliquot letter (a or b)  
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 71 of 84 
 
Shipment 
The samples will be transferred to the analytical laboratory after completion of the study or at 
mutually agreed upon time points during the clinical conduct of the study. The second set of 
samples will be shipped after the bioanalytical laboratory confirms receipt of the first set of 
samples. 
1. Samples will be packaged into cryoboxes and sorted by subject 
2. Before shipment, the samples will be appropriately packed in a cooler containing dry ice. 
Sufficient dry ice will be added to ensure that the samples will remain frozen for at least 
72 hours.  
3. The shipment will be accompanied by documentation containing the following information: 
name of the study drug product, protocol number, number of subjects, and number of 
samples included in the shipment. Expected samples that are not present will be identified. 
4. All frozen pharmacokinetic samples will be transferred with accompanying documentation to: 
Alliance Pharma, Inc. 
17 Lee Blvd 
Malvern, PA 19355 
Telephone:  610.296.3152 
Fax:  610.296.3153 
Contact name: Ruth Guan 
Contact E-mail: rguan@alliancepharmaco.com 
samples@alliancepharmaco.com  
 
Collection and Processing: Midazolam, Digoxin and TLD 
Plasma from whole blood Midazolam, Digoxin and TLD samples will be analyzed by Pyxant 
bioanalytical laboratory.  
A more detailed description of plasma sample preparation requirements may be provided by the 
analytical laboratory. If such a description is provided, the method of sample preparation 
provided by the laboratory shall supersede those provided in this protocol and appropriate 
documentation shall be placed in the Investigator Site File (ISF). 
 
 
 
 
 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 72 of 84 
 
Processing Instructions 
1 
Samples will be collected via direct venipuncture at the time points delineated in 
the appropriate Events Schedule (Section 13).  
2 
Blood will be drawn into pre-chilled evacuated tubes containing K2-EDTA and 
immediately placed on wet ice and then processed to plasma within 60 minutes. 
3 
Samples will be centrifuged at 1500 g at approximately 4°C (± 10 degrees) for 
10 minutes. After centrifugation, two aliquots of plasma will be removed and 
placed in appropriately labelled polypropylene vials. 
4 
The aliquots will be immediately placed on dry ice. Within 90 minutes of collection, 
the aliquots will be stored in a freezer set at -80°C ± 10°C and remain in the 
freezer until transferred for analysis. 
5 
Samples will be transferred at the agreed upon intervals. 
6 
The aliquots will be transferred on dry ice to the Pyxant bioanalytical laboratory for 
the determination of plasma concentrations of Midazolam and Digoxin using a 
validated procedure. 
7 
Blood sampling, plasma processing, and storage time will be documented in the 
study records. 
 
The samples will be transferred to the analytical laboratory after completion of the study or at 
mutually agreed upon time points during the clinical conduct of the study. The second set of 
samples will be shipped after the bioanalytical laboratory confirms receipt of the first set of 
samples. 
 
1. Samples will be packaged into cryoboxes and sorted by subject 
2. Before shipment, the samples will be appropriately packed in a cooler containing dry ice. 
Sufficient dry ice will be added to ensure that the samples will remain frozen for at least 
72 hours.  
3. The shipment will be accompanied by documentation containing the following information: 
name of the study drug product, protocol number, number of subjects, and number of 
samples included in the shipment. Expected samples that are not present will be identified. 
4. All frozen pharmacokinetic samples will be transferred with accompanying documentation to:  
Pyxant Labs Inc. 
4720 Forge Road 
Suite 108 Colorado Springs, CO 80907 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 73 of 84 
 
APPENDIX 2 DESCRIPTION AND COMPOSITION OF TEST PRODUCT  
TBAJ-876 Oral Suspension 
Description of the Dosage Form 
TBAJ-876 Oral Suspension is a compounded preparation at 5 mg/mL TBAJ-876 as tartrate, in 
ORA-Sweet® (or equivalent). The suspension is compounded at the clinical study site with 
TBAJ-876 tartrate and ORA-Sweet® (or equivalent), a commercially available flavored suspending 
vehicle.  
The required doses of the suspension drug product are dispensed using commercially available 
oral syringes of suitable capacity. 
Composition of the Drug Product 
The quantitative composition, function, and quality of each ingredient in the drug product 
(TBAJ-876 Oral Suspension, 5 mg/mL) is provided in the table below. 
 
Qualitative and Quantitative Composition of the TBAJ-876 Oral Suspension, 5 mg/mL 
Ingredient 
Function 
Quantity per Dose 
150 mg 
165 mg 
200 mg 
TBAJ-876 
free 
base 
(equivalent amount of TBAJ-
876 tartrate API1) 
Drug Substance 
150 mg (185.4 
mg) 
165 mg (203.9) 
200 mg (247.2 
mg) 
Ora-Sweet®,2 (or equivalent) 
Suspending 
vehicle 
q.s. to 30 mL 
q.s. to 33 mL 
q.s. to 40 mL 
Total Volume 
30 mL 
33mL 
40mL 
1TBAJ-876 equivalent calculated using the assay value of free base from the certificate of analysis. 
 
 
 
2Purified water, sucrose, glycerin, sorbitol, and flavoring.  Buffered with citric acid and sodium phosphate. Preserved 
with methylparaben and potassium sorbate. 
 
Container and Closure System 
TBAJ-876 tartrate drug substance is shipped to the clinical study site in double low density 
polyethylene (LDPE) bags, with each bag individually twist-tied. The bags are then placed in an 
aluminum foil polybag with a silica gel pack in the foil bag, and heat-sealed.  
TBAJ-876 Oral Suspension is transferred and stored in Pyrex glass reagent bottles with a 
polypropylene (PP) screw cap without a liner. These bottles are used for mixing, sampling, and 
storage prior to administration. 
Interaction Products 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 74 of 84 
 
Midazolam hydrochloride, Digoxin, Dolutegravir, Tenofovir disoproxil fumarate, Lamivudine will 
be obtained by TKL pharmacy in original manufacturing packaging. Individual doses will be 
prepared by TKL pharmacy as per manufacturing instructions. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 75 of 84 
 
APPENDIX 3 DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASE TOXICITY 
TABLE 
Division of Microbiology and Infectious Disease (DMID) Toxicity Table 
Source:  U.S. National Institute of Allergy and Infectious Diseases, DMID, November 
2007 (Draft) 
ABBREVIATIONS:  Abbreviations utilized in the Table: 
ULN = Upper Limit of Normal 
LLN = Lower Limit of Normal 
Rx = Therapy 
Req = Required 
Mod = Moderate 
IV = Intravenous 
ADL = Activities of Daily Living 
Dec = Decreased 
 
ESTIMATING SEVERITY GRADE 
For abnormalities NOT found elsewhere in the Toxicity Tables use the scale below to 
estimate grade of severity: 
Grade 
Severity Rating 
Definition 
GRADE 
1 
Mild 
Transient or mild discomfort (< 48 hours); no medical 
intervention/therapy required. 
GRADE 
2 
Moderate 
Mild to moderate limitation in activity - some assistance 
may be needed; no or minimal medical intervention/therapy 
required. 
GRADE 
3 
Severe 
Marked limitation in activity, some assistance usually 
required; medical intervention/therapy required, 
hospitalizations possible. 
GRADE 
4 
Potentially Life-
threatening 
Extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, 
hospitalization or hospice care probable. 
 
SERIOUS OR LIFE-THREATENING AEs 
ANY clinical event deemed by the clinician to be serious or life-threatening should be 
considered a grade 4 event. Clinical events considered to be serious or life-threatening 
include, but are not limited to: seizures, coma, tetany, diabetic ketoacidosis, 
disseminated intravascular coagulation, diffuse petechiae, paralysis, acute psychosis, 
severe depression. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 76 of 84 
 
COMMENTS REGARDING THE USE OF THESE TABLES 
• Standardized and commonly used toxicity tables (Division of AIDS, NCI’s Common 
Toxicity Criteria (CTC), and World Health Organization (WHO)) have been adapted 
for use by the Division of Microbiology and Infectious Diseases (DMID) and modified 
to better meet the needs of Patients in DMID trials. 
• For parameters not included in the following Toxicity Tables, sites should refer to the 
“Guide For Estimating Severity Grade” located above. 
• Criteria are generally grouped by body system. 
• Some protocols may have additional protocol specific grading criteria, which will 
supersede the use of these tables for specified criteria. 
HEMATOLOGY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
9.5 - 10.5 gm/dL 
8.0  - 9.4gm/dL 
6.5 - 7.9 gm/dL 
< 6.5 gm/dL 
Absolute Neutrophil 
Count 
1000-1500/mm3 
750-999/mm3 
500-749/mm3 
<500/mm3 
Platelets 
75,000-
99,999/mm3 
50,000-
74,999/mm3 
20,000-
49,999/mm3 
<20,000/mm3 
WBCs 
11,000-13,000/ 
mm3 
13,000-15,000 
/mm3 
15,000-
30,000/mm3 
>30,000 or <1,000 
/mm3 
% Polymorphonuclear 
Leucocytes + Band 
Cells 
> 80% 
90 – 95% 
>95% 
---------- 
Abnormal Fibrinogen 
Low: 
100-200 mg/dL 
High: 
400-600 mg/dL 
Low: 
<100 mg/dL 
High: 
>600 mg/dL 
Low: 
< 50 mg/dL 
 
---------- 
Fibrinogen 
associated with 
gross bleeding or 
with disseminated 
coagulation 
Fibrin Split Product 
20-40 mcg/ml 
41-50 mcg/ml 
51-60 mcg/ml 
> 60 mcg/ml 
Prothrombin Time (PT) 
1.01 - 1.25 x ULN 
1.26-1.5 x ULN 
1.51 -3.0 x ULN 
>3 x ULN 
Activated Partial 
Thromboplastin (APPT) 
1.01 -1.66 x ULN 
1.67 - 2.33 x ULN 
2.34 - 3 x ULN 
> 3 x ULN 
Methemoglobin 
5.0 - 9.9 % 
10.0 - 14.9 % 
15.0 - 19.9% 
> 20.0 % 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 77 of 84 
 
CHEMISTRIES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hyponatremia 
130-135 mEq/L 
123-129 mEq/L 
116-122 mEq/L 
< 116 mEq/L or abnormal 
sodium with mental status 
changes or seizures 
Hypernatremia 
146-150 mEq/L 
151-157 mEq/L 
158-165 mEq/L 
> 165 mEq/L or abnormal 
sodium with mental status 
changes or seizures 
Hypokalemia 
3.0 - 3.4 mEq/L 
2.5 - 2.9 mEq/L 
2.0 - 2.4 mEq/L or 
intensive 
replacement 
therapy or 
hospitalization 
required 
< 2.0 mEq/L or abnormal 
potassium with paresis, 
ileus or life-threatening 
arrhythmia 
Hyperkalemia 
5.6 - 6.0 mEq/L 
6.1 - 6.5 mEq/L 
6.6 - 7.0 mEq/l 
> 7.0 mEq/L or abnormal 
potassium with life-
threatening arrhythmia 
Hypoglycemia 
55-64 mg/dL 
40-54 mg/dL 
30-39 mg/dL 
<30 mg/dL or abnormal 
glucose with mental status 
changes or coma 
Hyperglycemia 
(non-fasting and no 
prior diabetes) 
116 - 160 mg/dL 
161- 250 mg/dL 
251 - 500 mg/dL 
> 500 mg/dL or abnormal 
glucose with ketoacidosis or 
seizures 
Hypocalcemia 
(corrected for 
albumin) 
8.4 - 7.8 mg/dL 
7.7 - 7.0 mg/dL 
6.9 - 6.1 mg/dL 
< 6.1 mg/dL or abnormal 
calcium with life threatening 
arrhythmia or tetany 
Hypercalcemia 
(correct for albumin) 
10.6 - 11.5 mg/dL 
11.6 - 12.5 
mg/dL 
12.6 - 13.5 mg/dL 
> 13.5 mg/dL or abnormal 
calcium with life threatening 
arrhythmia 
Hypomagnesemia 
1.4 - 1.2 mEq/L 
1.1 - 0.9 mEq/L 
0.8 - 0.6 mEq/L 
< 0.6 mEq/L or abnormal 
magnesium with life-
threatening arrhythmia 
Hypophosphatemia 
2.0 - 2.4 mg/dL 
1.5 -1.9 mg/dL 
or replacement 
Rx required 
1.0 -1.4 mg/dL 
intensive therapy 
or hospitalization 
required 
< 1.0 mg/dL or abnormal 
phosphate with life-
threatening arrhythmia 
Hyperbilirubinemia 
(when accompanied 
by any increase in 
other liver function 
test) 
1.1 - <1.25 x ULN 
1.25 - <1.5 x 
ULN 
1.5 – 1.75 x ULN 
> 1.75 x ULN 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 78 of 84 
 
CHEMISTRIES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hyperbilirubinemia 
(when other liver 
function are in the  
normal range) 
1.1 - <1.5 x ULN 
1.5 - <2.0 x 
ULN 
2.0 – 3.0 x ULN 
> 3.0 x ULN 
BUN 
1.25 - 2.5 x ULN 
2.6 - 5 x ULN 
5.1 - 10 x ULN 
> 10 x ULN 
Hyperuricemia (uric 
acid) 
7.5 – 10.0 mg/dL 
10.1 – 12.0 
mg/dL 
12.1 – 15.0 mg/dL 
>15.0 mg/dL 
Creatinine 
1.1 - 1.5 x ULN 
1.6 - 3.0 x ULN 
3.1 - 6 x ULN 
> 6 x ULN or dialysis 
required 
 
ENZYMES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
AST (SGOT) 
1.1 - <2.0 x ULN 
2.0 – <3.0 x ULN 
3.0 – 8.0 x ULN 
> 8 x ULN 
ALT (SGPT) 
1.1 - <2.0 x ULN 
2.0 – <3.0 x ULN 
3.0 – 8.0 x ULN 
> 8 x ULN 
GGT 
1.1 - <2.0 x ULN 
2.0 – <3.0 x ULN 
3.0 – 8.0 x ULN 
> 8 x ULN 
Alkaline Phosphatase 
1.1 - <2.0 x ULN 
2.0 – <3.0 x ULN 
3.0 – 8.0 x ULN 
> 8 x ULN 
Amylase 
1.1 - 1.5 x ULN 
1.6 - 2.0 x ULN 
2.1 - 5.0 x ULN 
> 5.1 x ULN 
Lipase  
1.1 - 1.5 x ULN 
1.6 - 2.0 x ULN 
2.1 - 5.0 x ULN 
> 5.1 x ULN 
 
URINALYSIS 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Proteinuria 
1+ or 200 mg - 1 
gm loss/day 
2-3+ or 1- 2 gm 
loss/day 
4+ or 2-3.5 gm 
loss/day 
nephrotic 
syndrome or > 3.5 
gm loss/day 
Hematuria* 
microscopic only 
<10 rbc/hpf 
gross, no clots >10 
rbc/hpf 
gross, with or 
without clots, OR 
red blood cell 
casts 
obstructive or 
required 
transfusion 
*Assessment does not apply if a subject is on menses. 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 79 of 84 
 
CARDIOVASCULAR 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cardiac Rhythm 
 
asymptomatic, 
transient signs, no 
Rx required 
recurrent/persistent; 
symptomatic Rx 
required 
unstable 
dysrythmia; 
hospitalization 
and treatment 
required 
Hypertension 
transient increase 
> 20 mm/Hg; no 
treatment1 
recurrent, chronic 
increase > 
20mm/Hg. 
/treatment required 
acute treatment 
required; outpatient 
treatment or 
hospitalization 
possible 
end organ 
damage or 
hospitalization 
required 
Hypotension 
transient 
orthostatic 
hypotension with 
heart rate 
increased by <20 
beat/min or 
decreased by <10 
mm Hg systolic 
BP, No treatment 
required1 
symptoms due to 
orthostatic 
hypotension or BP 
decreased by <20 
mm Hg systolic; 
correctable with 
oral fluid treatment 
requires IV fluids; no 
hospitalization 
required 
mean arterial 
pressure <60mm/ 
Hg or end organ 
damage or shock;   
requires 
hospitalization 
and vasopressor 
treatment 
Pericarditis 
minimal effusion 
mild/moderate 
asymptomatic 
effusion, no 
treatment 
symptomatic 
effusion; pain; EKG 
changes 
tamponade; 
pericardiocentesis 
or surgery 
required 
Hemorrhage, Blood 
Loss 
microscopic/occult 
mild, no transfusion 
gross blood loss; 1-2 
units transfused 
massive blood 
loss; > 3 units 
transfused 
 
RESPIRATORY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cough 
Transient - no 
treatment 
persistent cough; 
treatment responsive 
Paroxysmal cough; 
uncontrolled with 
treatment 
-------------------- 
Bronchospasm, 
Acute 
transient; no 
treatment; 70% - 
80% FEV1 of peak 
flow 
requires treatment; 
normalizes with 
bronchodilator; FEV1 
50% - 70% (of peak 
flow) 
no normalization with 
bronchodilator;FEV1 
25% - 50% of peak 
flow; or  retractions 
present 
cyanosis: FEV1 < 
25% of peak flow 
or intubation 
necessary 
Dyspnea 
dyspnea on exertion 
dyspnea with normal 
activity 
dyspnea at rest 
dyspnea requiring 
Oxygen therapy 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 80 of 84 
 
GASTROINTESTINAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Nausea 
mild or transient; 
maintains 
reasonable intake 
moderate 
discomfort; intake 
decreased 
significantly; some 
activity limited 
no significant 
intake; requires IV 
fluids 
hospitalization 
required; 
Vomiting 
1 episode in 24 
hours 
2-5 episodes in 24 
hours 
>6 episodes in 24 
hours or needing 
IV fluids 
physiologic 
consequences 
requiring 
hospitalization or 
requiring 
parenteral nutrition 
Constipation 
requiring stool 
softener or dietary 
modification 
requiring laxatives 
obstipation 
requiring manual 
evacuation or 
enema 
obstruction or toxic 
megacolon 
Diarrhea 
mild or transient; 
3-4 loose 
stools/day or mild 
diarrhea last < 1 
week 
moderate or 
persistent; 5-7 
loose stools/day or 
diarrhea lasting >1 
week 
>7 loose 
stools/day or 
bloody diarrhea; or 
orthostatic 
hypotension or 
electrolyte 
imbalance or >2L 
IV fluids required  
hypotensive shock 
or physiologic 
consequences 
requiring 
hospitalization   
Oral 
Discomfort/Dysphagia 
mild discomfort; no 
difficulty 
swallowing 
some limits on 
eating/drinking 
eating/talking very 
limited; unable to 
swallow solid 
foods 
unable to drink 
fluids; requires IV 
fluids 
 
NEUROLOGICAL 
 
Grade 1  
Grade 2  
Grade 3  
Grade 4  
Neuro-Cerebellar 
slight 
incoordination 
dysdiadochokinesis 
intention tremor, 
dysmetria, slurred 
speech; nystagmus 
locomotor ataxia 
incapacitated 
Psychiatric 
mild anxiety or 
depression 
moderate anxiety or 
depression; therapy 
required; change in 
normal routine 
severe mood 
changes requiring  
therapy; or suicidal 
ideation;  or 
aggressive 
ideation 
acute psychosis 
requiring 
hospitalization;  or 
suicidal 
gesture/attempt or 
hallucinations 
Muscle Strength 
Subjective 
weakness no 
objective 
symptoms/ signs 
mild objective 
signs/symptoms no 
decrease in 
function 
objective 
weakness function 
limited 
paralysis 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 81 of 84 
 
NEUROLOGICAL 
 
Grade 1  
Grade 2  
Grade 3  
Grade 4  
Paresthesia (burning, 
tingling, etc.) 
mild discomfort; no 
treatment  required 
moderate 
discomfort; non-
narcotic analgesia 
required 
severe discomfort; 
or narcotic 
analgesia required 
with symptomatic 
improvement 
incapacitating; or 
not responsive to 
narcotic analgesia 
Neuro-sensory 
mild impairment in 
sensation 
(decreased 
sensation, e.g., 
vibratory, pinprick, 
hot/cold in great 
toes) in focal area 
or symmetrical 
distribution; or 
change in taste, 
smell, vision and/or 
hearing 
moderate 
impairment (mod 
decreased 
sensation, e.g., 
vibratory, pinprick, 
hot/cold to ankles) 
and/or joint position 
or mild impairment 
that is not 
symmetrical 
severe impairment 
(decreased or loss 
of sensation to 
knees or wrists) or 
loss of sensation 
of at least mod 
degree in multiple 
different body 
areas (i.e., upper 
and lower 
extremities) 
sensory loss 
involves limbs and 
trunk; paralysis;  or 
seizures 
 
 
 
MUSCULOSKELETAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Arthralgia (joint pain) 
mild pain not 
interfering with 
function 
moderate pain, 
analgesics and/or 
pain interfering with 
function but not with 
activities of daily 
living 
severe pain; pain 
and/or analgesics 
interfering with 
activities of daily 
living 
disabling pain 
Arthritis 
mild pain with 
inflammation, 
erythema or joint 
swelling – but not 
interfering with 
function 
moderate pain with 
inflammation, 
erythema or joint 
swelling – 
interfering with 
function, but not 
with activities of 
daily living 
severe pain with 
inflammation, 
erythema or joint 
swelling –and 
interfering with 
activities of daily 
living 
permanent 
and/or disabling 
joint destruction 
Myalgia 
myalgia with no 
limitation of activity 
muscle tenderness 
(at other than 
injection site) or 
with moderate 
impairment of 
activity 
severe muscle 
tenderness with 
marked impairment 
of activity 
frank 
myonecrosis 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 82 of 84 
 
SKIN 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Mucocutaneous 
erythema; pruritus 
diffuse, maculo 
papular rash, dry 
desquamation 
vesiculation or moist 
desquamation or 
ulceration 
exfoliative 
dermatitis, mucous 
membrane 
involvement or 
erythema, 
multiforme or 
suspected Stevens-
Johnson or  
necrosis requiring 
surgery 
Induration 
< 15mm  
15-30 mm 
>30mm 
 
Erythema 
< 15mm  
15-30 mm 
>30mm 
 
Edema 
< 15mm  
15-30 mm 
>30mm 
 
Rash at Injection 
Site 
< 15mm  
15-30 mm 
>30mm 
 
Pruritus 
slight itching at 
injection site 
moderate itching at 
injection extremity 
itching over entire 
body 
 
 
 
SYSTEMIC 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Allergic Reaction 
pruritus without rash 
localized urticaria 
generalized 
urticaria; 
angioedema 
anaphylaxis 
Headache 
mild, no treatment 
required 
transient, moderate; 
treatment required 
severe; responds to 
initial narcotic 
therapy 
intractable; requires 
repeated narcotic 
therapy 
Fever: oral 
37.7 - 38.5 C or 
100.0 - 101.5 F 
38.6 - 39.5 C or 
101.6 - 102.9 F 
39.6 - 40.5 C or 103 
- 105 F 
> 40 C or > 105 F 
Fatigue 
normal activity 
reduced < 48 hours 
 normal activity 
decreased 25- 50% 
> 48 hours 
normal activity 
decreased > 50% 
can’t work 
unable to care for 
self 
 
 
 


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 83 of 84 
 
 
A. Tables for Laboratory Abnormalities  
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate.  
Serum *  
Mild (Grade 1)  Moderate 
(Grade 2)  
Severe (Grade 
3)  
Potentially Life 
Threatening  
(Grade 4)**  
Sodium – Hyponatremia mEq/L  
132 – 134  
130 – 131  
125 – 129  
< 125   
Sodium – Hypernatremia mEq/L  
144 – 145   
146 – 147   
148 – 150   
> 150   
Potassium – Hyperkalemia mEq/L  5.1 – 5.2   
5.3 – 5.4  
5.5 – 5.6  
> 5.6   
Potassium – Hypokalemia mEq/L  
3.5 – 3.6  
3.3 – 3.4  
3.1 – 3.2  
< 3.1   
Glucose – Hypoglycemia mg/dL  
65 – 69  
55 – 64  
45 – 54  
< 45   
Glucose – Hyperglycemia  
Fasting – mg/dL  
Random – mg/dL  
  
100 – 110  
110 – 125  
  
111 – 125  
126 – 200  
  
>125  
>200  
Insulin requirements or 
hyperosmolar coma  
Blood Urea Nitrogen BUN mg/dL  
23 – 26  
27 – 31  
> 31  
Requires dialysis  
Creatinine – mg/dL  
1.5 – 1.7  
1.8 – 2.0  
2.1 – 2.5  
> 2.5 or requires 
dialysis  
Calcium – hypocalcemia mg/dL  
8.0 – 8.4  
7.5 – 7.9  
7.0 – 7.4  
< 7.0   
Calcium – hypercalcemia mg/dL  
10.5 – 11.0  
11.1 – 11.5  
11.6 – 12.0  
> 12.0   
Magnesium – hypomagnesemia 
mg/dL  
1.3 – 1.5  
1.1 – 1.2  
0.9 – 1.0  
< 0.9   
Phosphorous – 
hypophosphatemia mg/dL  
2.3 – 2.5  
2.0 – 2.2  
1.6 – 1.9  
< 1.6   
CPK – mg/dL  
1.25 – 1.5 x 
ULN***  
1.6 – 3.0 x ULN  
3.1 –10 x ULN  
> 10 x ULN  
Albumin – Hypoalbuminemia g/dL  2.8 – 3.1  
2.5 – 2.7  
< 2.5   
--  
Total Protein – Hypoproteinemia 
g/dL  
5.5 – 6.0  
5.0 – 5.4  
< 5.0   
--  
Alkaline phosphate – 
increase by factor  
1.1 – 2.0 x 
ULN  
2.1 – 3.0 x ULN  
3.1 – 10 x ULN  
> 10 x ULN  
Liver Function Tests –ALT, AST 
increase by factor  
1.1 – 2.5 x 
ULN  
2.6 – 5.0 x ULN  
5.1 – 10 x ULN  
> 10 x ULN  
Bilirubin – when accompanied by 
any increase in Liver Function 
Test increase by factor  
1.1 – 1.25 x 
ULN  
1.26 – 1.5 x 
ULN  
1.51 – 1.75 x 
ULN  
> 1.75 x ULN  
Bilirubin – when Liver Function 
Test is normal; increase by factor  
1.1 – 1.5 x 
ULN  
1.6 – 2.0 x ULN  
2.0 – 3.0 x ULN  
> 3.0 x ULN  
Cholesterol  
201 – 210  
211 – 225  
> 226  
---  
Pancreatic enzymes – amylase, 
lipase  
1.1 – 1.5 x 
ULN  
1.6 – 2.0 x ULN  
2.1 – 5.0 x ULN  
> 5.0 x ULN  
*   The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters.  Institutional normal reference ranges should be provided to demonstrate that they are appropriate.  
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of the 
laboratory abnormalities as Potentially Life Threatening (Grade 4).  For example. a low sodium value that falls within a 
grade 3 parameter (125-129 mE/L) should be recorded as a grade 4 hyponatremia event if the participant had a new 
seizure associated with the low sodium value.  
***ULN” is the upper limit of the normal range.  


TB Alliance 
Protocol Name/Number: TBAJ-876-CL002 
Protocol Version: V1.0/ 20 May22 
 
TMP-C-SOP01-B V1.0 30-JAN-2019 
 
CONFIDENTIAL 
Page 84 of 84 
 
Hematology *  
Mild (Grade 1)  
Moderate  
Grade 2)  
Severe  
(Grade 3)  
Potentially Life  
Threatening  
(Grade 4)  
Hemoglobin (Female) - gm/dL  
11.0 - 12.0  
9.5 - 10.9  
8.0 - 9.4  
< 8.0  
Hemoglobin (Female) change 
from baseline value -  gm/dL  
Any decrease - 1.5  1.6 - 2.0  
2.1 - 5.0  
> 5.0  
Hemoglobin (Male) - gm/dL  
12.5 – 13.5  
10.5 - 12.4  
8.5 - 10.4  
< 8.5  
Hemoglobin (Male) change 
from baseline value – gm/dL  
Any decrease - 1.5  1.6 - 2.0  
2.1 - 5.0  
> 5.0  
WBC Increase - cell/mm3 
10,800 - 15,000  
15,001 - 20,000   
20,001 - 25, 000  
> 25,000  
WBC Decrease - cell/mm3 
2,500 - 3,500  
1,500 - 2,499  
1,000 - 1,499  
< 1,000  
Lymphocytes Decrease - 
cell/mm3 
750 - 1,000  
500 - 749  
250 - 499  
< 250  
Neutrophils Decrease - 
cell/mm3 
1,500 - 2,000  
1,000 - 1,499  
500 - 999  
< 500  
Eosinophils - cell/mm3 
650 - 1500  
1501 - 5000  
> 5000  
Hypereosinophilic 
syndrome  
Platelets Decreased - cell/mm3 
125,000 - 140,000  
100,000 - 124,000  
25,000 - 99,000  
< 25,000  
PT – increase by factor 
(prothrombin time)  
1.0 - 1.10 x ULN**  
1.11 - 1.20 x ULN  
1.21 - 1.25 x ULN  > 1.25 ULN  
PTT – increase by factor  
(partial thromboplastin time)  
1.0 - 1.2 x ULN  
1.21 - 1.4 x ULN  
1.41 - 1.5 x ULN  
> 1.5 x ULN  
Fibrinogen increase - mg/dL  
400 - 500   
501 - 600   
> 600   
--  
Fibrinogen decrease - mg/dL  
150 - 200  
125 - 149  
100 - 124  
< 100 or 
associated with 
gross bleeding or 
disseminated 
intravascular 
coagulation (DIC)  
*  
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters.  Institutional normal reference ranges should be provided to demonstrate that they are appropriate.  
**    “ULN” is the upper limit of the normal range.  
 
Urine *  
Mild (Grade 1)  Moderate 
(Grade 2)  
Severe (Grade 3)  
Potentially Life Threatening  
(Grade 4)  
Protein  
Trace  
1+  
2+  
Hospitalization or dialysis  
Glucose  
Trace  
1+  
2+  
Hospitalization for 
hyperglycemia  
Blood (microscopic) - red 
blood cells per high 
power field (RBC/hpf) 
1 - 10  
11 – 50  
> 50 and/or gross 
blood  
Hospitalization or packed red 
blood cells (PRBC) 
transfusion  
*  
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters.  Institutional normal reference ranges should be provided to demonstrate that they are appropriate.  

SAP_001.pdf: 
Table of Contents
Table of Contents ....................................................................................................................................................................
List of Abbreviations and Definitions of Terms ........................................................................................................................
1.  INTRODUCTION ................................................................................................................................................................
2. STUDY OBJECTIVES .........................................................................................................................................................
3. STUDY DESIGN .................................................................................................................................................................
4. HARDWARE AND SOFTWARE .........................................................................................................................................
5. STATISTICAL DATA REVIEW ............................................................................................................................................
6. DATABASE CLOSURE .......................................................................................................................................................
7. SAMPLE SIZE DETERMINATION ......................................................................................................................................
8. HANDLING OF MISSING DATA .........................................................................................................................................
9. ANALYSIS POPULATIONS ................................................................................................................................................
10. STATISTICAL EVALUATION ............................................................................................................................................
10.1 Subject Disposition .....................................................................................................................................................
10.2 Demographic and Other Covariates ...........................................................................................................................
10.3 Pharmacokinetics Evaluations ...................................................................................................................................
10.4 Safety Evaluations .....................................................................................................................................................
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES ...............................................................................
12. HEADINGS ......................................................................................................................................................................
13. ARCHIVING AND RETENTION OF DOCUMENTS ........................................................................................................
15. OUTLINE OF PROPOSED TABLES, FIGURES AND LISTINGS ...................................................................................
3
4
5
5
5
7
8
8
8
8
8
9
9
9
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TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
Table of Contents 
Table of Contents ...........................................................................................................................2 
List of Abbreviations and Definitions of Terms ..........................................................................3 
1. 
INTRODUCTION ..................................................................................................................4 
2. 
STUDY OBJECTIVES ..........................................................................................................4 
3. 
STUDY DESIGN ....................................................................................................................4 
4. 
HARDWARE AND SOFTWARE ........................................................................................6 
5. 
STATISTICAL DATA REVIEW .........................................................................................7 
6. 
DATABASE CLOSURE .......................................................................................................7 
7. 
SAMPLE SIZE DETERMINATION ...................................................................................7 
8. 
HANDLING OF MISSING DATA ......................................................................................7 
9. 
ANALYSIS POPULATIONS ...............................................................................................7 
10. STATISTICAL EVALUATION ...........................................................................................8 
10.1 Subject Disposition ........................................................................................................8 
10.2 Demographic and Other Covariates ...............................................................................8 
10.3 Pharmacokinetics Evaluations .......................................................................................8 
10.4 Safety Evaluations .......................................................................................................10 
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES .........................11 
12. HEADINGS ..........................................................................................................................11 
13. ARCHIVING AND RETENTION OF DOCUMENTS ....................................................12 
 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
List of Abbreviations and Definitions of Terms 
Abbreviation 
 
Definition 
ADaM 
 
Analysis Data Model 
AE 
 
Adverse Event 
ANOVA 
 
Analysis of variance 
AUC 
 
Area under the curve 
CI 
 
Confidence interval 
CRF 
 
Case Report Form 
DMP 
 
Data Management Plan 
ECG 
 
Electrocardiogram 
ET 
 
Early termination 
GMR 
 
Ratio of geometric means 
ODS 
 
Output Delivery System 
PK 
 
Pharmacokinetics 
PT 
 
Preferred Term 
RTF 
 
Rich-Text Format 
SAE 
 
Serious Adverse Event 
SAP 
 
Statistical Analysis Plan 
SDTM 
 
Study Data Tabulation Model 
SOC 
 
System Organ Class 
SOP 
 
Standard Operating Procedure 
TEAE 
 
Treatment-emergent adverse event 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the study protocol dated 20 May 2022. This 
document specifies, in advance of data collection, a comprehensive description of the 
analysis methods planned to achieve the study objectives specified in the study protocol. Two 
sequential study phases are planned, with the performance of the second phase conditional on 
the outcome of the first. The present document will show the planned data presentations, 
summaries, and analyses for the initial phase of the study. A similar document will be 
prepared separately in the event that the study enters its second phase. 
2. STUDY OBJECTIVES 
The primary objective of the study is to evaluate the induction potential of TBAJ-876 on 
CYP3A4 and P-glycoprotein and the inhibition potential of TBAJ-876 on P-glycoprotein in 
healthy adult subjects. 
The secondary objective of the study is to evaluate the effects of multiple-dose 
administrations of TBAJ-876 on the safety and tolerability of midazolam and digoxin. An 
extension of the study is planned conditionally on the outcomes of the initial phase, the 
objective of which will be to evaluate the effects of multiple-dose administration of TBAJ-
876 on the safety and tolerability of an antiretroviral regimen. 
3. STUDY DESIGN 
This is a phase 1, open-label, single-center, drug-drug interaction study. Two sequential 
study phases are planned. The performance of the second phase is conditional on the 
outcome of the first. The planned enrollment to the first phase of the study is 28 healthy 
males and females between 18 and 55 years of age. This phase of the study will last 34 days 
for each subject, from Check-in on Day í1 through completion of the clinical procedures on 
Day 25 and a follow-up phone call on Day 32. 
Subjects will be screened for eligibility to participate in the study up to 21 days prior to 
admission to the study center on Day í1. Eligible subjects will be admitted to the study 
center on Day í1 and will be confined there under observation until they are discharged on 
Day 25. Following discharge, subjects will receive a follow-up phone call on Day 32. 
 
 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
All subjects will receive treatment with single daily doses according to the following 
schedule: 
Day 1 
Midazolam oral syrup, 2 mg 
Fasted 
Day 2 
Digoxin tablet, 0.25 mg 
Fasted 
Day 6 – 13 
TBAJ-876 oral suspension, 200 mg 
Fed 
Day 14 – 19 
TBAJ-876 oral suspension, 165 mg 
Fed 
Day 20 
Midazolam oral syrup, 2 mg; TBAJ-876 oral suspension, 200 
mg 
Fasted 
Day 21 
Digoxin tablet, 0.25 mg; TBAJ-876 oral suspension, 200 mg 
Fasted 
Day 22 – 24 
TBAJ-876 oral suspension, 150 mg 
Fed 
The following safety assessments will be performed at scheduled time points throughout the 
study: 
Physical examinations 
Screening and Days í1, 2, 3, 4, 5, and 25, or early 
withdrawal. 
Vital signs (blood pressure, heart 
rate [pulse], temperature, and 
respiration rate, pulse oximetry) 
Screening and Days í1 
Pre-dose and 0.5, 1, 2, 6, and 12 hours post-dose on 
Days 1, 2, 6, 20, and 21 
6 hours post-dose on Days 7 through 19 
Days 24 and 25, or early withdrawal. 
Electrocardiogram (ECG) 
Once at Screening and Days í1, 3, 7, 20, 22, and 25, 
or upon early withdrawal; also on Days 2 and 21, pre-
dose and 0.5, 1, 2, 6, and 12 hours post-dose. 
Adverse events (AEs) 
Ongoing collection throughout the study period. 
Clinical laboratory tests 
(hematology, serum chemistry, 
coagulation, and urinalysis) 
Screening and Days í1, 2, 3, 7, 20, 21, 22, and 25, or 
upon early withdrawal. 
 
 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
Blood samples will be taken according to the following schedule for determination of plasma 
concentrations of the corresponding analytes: 
Day 1 
Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 
12, 24 hours 
Midazolam and its metabolite 
1-hydroxymidazolam 
Day 2 
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 
24, 48, 72, 96 hours 
Digoxin 
Day 17 
Pre-dose, 0.5, 3, 4, 5, 6, 7, 8, 12, 
16, 20, 24 hours 
TBAJ-876 and its metabolites M2 and 
M3 
Day 20 
Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 
12, 24 hours 
Midazolam and its metabolite 
1-hydroxymidazolam 
Day 21 
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 
24, 48, 72, 96 hours 
Digoxin 
4. HARDWARE AND SOFTWARE 
Statistical analysis will be performed following TKL standard operating procedures (SOPs) 
and on the TKL computer network. All statistical analyses will be performed using SAS 
Version 9.4 or higher with program code prepared specifically for the project by qualified 
TKL statisticians and SAS programmers. 
The SAS programs will generate rich-text-formatted (RTF) output with the “RTF” extension 
using the SAS Output Delivery System (ODS). The summary tables and listings will be 
formatted using the Times New Roman font. The RTF output is included in report documents 
prepared with Microsoft Word and converted to PDF format without typographical change. 
Study data tabulation model (SDTM) data sets and required analysis data model (ADaM) 
data sets will be created and taken as input to validated SAS programs to generate the report-
ready tables, listings, and figures. Each output display will show the names of the data sets 
and SAS program used to produce it. Upon completion of the study report, the data sets will 
be provided to the sponsor as SAS XPT transport files with define.xml files including details 
of all derivations and imputations used.  


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
5. STATISTICAL DATA REVIEW  
Data verification activities to be performed prior to delivery of the SAS data sets to the 
project statistician are described in the approved Data Management Plan (DMP). After 
completion of the data verification activities, the SAS data sets will be reviewed by the 
project statistician along with documentation of any unresolved queries and data conventions 
applied that are not fully explained in the data or in the DMP. The project statistician will 
perform completeness and self-consistency checks of the study data. These checks will be 
selected to ensure the self-consistency of dates and events in the subject record, the 
consistency of all reported data values with expected ranges, and, if not within range, the 
presence in the subject record of explanatory comments or other corroborative data. Overall, 
each subject’s record in the study database must convey a full but concise description of the 
subject’s experience with respect to protocol-specific events. Questions will be issued to the 
Data Manager and resolved before closure of the database. 
6. DATABASE CLOSURE 
After completion of all data review procedures, validation of the project database (ie, all 
those activities and operations designed and performed to ensure that the database is a 
complete and accurate representation of protocol-specific events), and approval of the data 
review document by the study sponsor, the clinical database will be closed (ie, “locked”). 
Any change to the clinical database after this time will require written authorization, with 
explanation, by the Sponsor and the Biostatistician, in conformance with TKL SOPs. 
7. SAMPLE SIZE DETERMINATION 
The study sample size for this Phase 1 study is based on statistical power calculations as 
detailed in the study protocol, section 10.2. 
8. HANDLING OF MISSING DATA  
In this study, there will be no imputations of missing data points. All data will be reported 
and analyzed as observed values only. 
9. ANALYSIS POPULATIONS 
The analysis populations will be determined according to available data. Relevant data for all 
subjects enrolled to the study will be reported. The Safety population for analysis of adverse 
events, clinical laboratory test results, and other safety-related variables will include all 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
subjects who received treatment with any one of the study drugs. The Pharmacokinetics (PK) 
population for analysis of plasma concentration data and pharmacokinetic parameters will 
include all subjects presenting data sufficient to calculate the analysis parameter. In case a 
subject cannot be included in a particular analysis, the rationale for the omission of that 
subject will be fully explained in the study report. 
10. STATISTICAL EVALUATION 
10.1 
Subject Disposition 
Subject disposition will be summarized by showing the number of subjects screened, and the 
number and percent of screen failures and enrolled subjects; the number and percent of 
subjects completed and discontinued, along with the primary reason for discontinuation. By-
subject listings will include date of informed consent, date of screening, date-time of 
enrollment, date of last visit, date of last contact, and reason for discontinuation. Individual 
subject data for any protocol deviations will also be presented in a by-subject listing. 
10.2 
Demographic and Other Covariates 
Subject age, height, weight, and BMI will be summarized for the Safety population as mean, 
standard deviation, median, minimum, and maximum. Sex, race, and ethnicity will be 
summarized as number and percent of subjects in each category. Subject listings will include 
age, sex, race, ethnicity, weight, height, and body mass index. 
Prior (prior to the start of treatment) medication use and concomitant (after the start of 
treatment) medication use will be summarized separately. If the end date of a prior 
medication occurs after treatment starts, then the medication will be reported in both the prior 
and concomitant tables and listings. These tables will present the number and percentage of 
subjects for each medication. Medication terms will be coded and classified according to the 
WHO Drug Dictionary, Version B3 (March 2022). 
Data listings will also be provided to show medical history, childbearing potential and 
pregnancy test results, and general investigator comments. 
10.3 
Pharmacokinetics Evaluations 
Plasma concentrations will be summarized at each time point for each measured analyte as 
mean, standard deviation, median, coefficient of variation, standard error of the mean, 
minimum and maximum. Individual subject data will be plotted against time post-dose on 
linear and log-linear axes. Day 1 and Day 20 midazolam concentrations, and Day 2 and 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
Day 21 digoxin concentrations, will be overlayed on a single set of axes to permit visual 
comparison. Similar displays will be constructed for the mean concentrations of each analyte 
over time post-dose. 
The following pharmacokinetics parameters will be determined for each subject and study 
day for midazolam, 1-hydroxymidazolam, and digoxin: 
x AUC0-last, the area under the curve of plasma concentration vs time post-dose, 
approximated trapezoidally, from 0 to the time of last measurable concentration; 
x Cmax, the maximum observed concentration; 
x tmax, the time post-dose of the maximum observed concentration. 
The individual subject plots of each analyte concentration vs time will be inspected visually 
to identify log-linear terminal segments corresponding to an exponential elimination phase. If 
at least 3 observations are presented along what appears to be a terminal elimination phase, 
then the elimination rate constant will be estimated using a linear regression fit to the plot of 
log concentration vs time during this phase. The value of the elimination rate constant, kel, is 
the absolute magnitude of the estimated slope. 
Using the following SAS code, 
proc 
reg 
outest=KOUT;  
model 
LOGCONC 
= 
TIME;  
quit; 
 
the value of kel is computed as ABS(TIME) in the dataset KOUT, and the value of the 
elimination half-life, t1/2, is LOG(2)/KEL. 
When kel and t1/2 are estimated, the following additional parameters will be computed: 
x AUC0-inf, the area under the curve of plasma concentration vs time post-dose, 
extrapolated to infinite time, calculated as AUC0-last + Clast/kel; 
x CL/F, total apparent drug clearance rate, defined as oral dose / AUC0-inf; (Note that 
when oral dose is provided in units of mg, the AUC must be converted to units of 
mg.hr/L.) 
x VZ/F, apparent volume of distribution, defined as CL/F divided by kel. 
In addition to mean, standard deviation, median, minimum, and maximum, the AUC 
parameters and Cmax will be summarized by treatment group as geometric mean and 
coefficient of variation (ie, 100*SQRT( EXP(VAR) - 1 ) with VAR= the variance of the log-


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
transformed values).   Elimination rate constant, half-life, and tmax will be summarized as 
median, minimum, and maximum. Drug clearance and volume of distribution will be 
summarized as mean, standard deviation, minimum, and maximum. 
To compare pharmacokinetic parameters of the interaction products with TBAJ-876 versus 
alone, analyses of variance (ANOVA) will be performed using SAS PROC MIXED. The 
model will include subject as a random effect and treatment (with TBAJ-876 versus alone) as 
a fixed effect. Geometric least-squares mean values and 95% confidence intervals (CIs) will 
be tabulated for AUC0-inf and Cmax. The ratio of geometric means (GMR) will be computed 
comparing co-administration with TBAJ-876 versus alone, along with the 90% 2-sided CI. 
The test drug TBAJ-876 will be considered a moderate inducer of CYP3A4 if the estimated 
GMR of midazolam AUC0-inf is less than 0.50. It will be considered a moderate inducer of 
P-glycoprotein if the estimated GMR of digoxin AUC0-inf is less than 0.50. If the estimated 
GMR of digoxin AUC0-inf is 2.0 or greater, then TBAJ-876 will be considered a moderate 
inhibitor of P-glycoprotein. These results will be used to decide whether to conduct the 
second phase of the study. 
The following pharmacokinetics parameters will be determined for each subject for TBAJ-
876 and its metabolites M2 and M3 on Day 17: 
x AUC0-24, the area under the curve of plasma concentration vs time post-dose, 
approximated trapezoidally, from 0 to 24 hours post-dose; 
x Cmax, the maximum observed concentration; 
x tmax, the time post-dose of the maximum observed concentration. 
x Ctrough, the observed pre-dose concentration. 
The sum of AUC0-24 for TBAJ-876 and its M3 metabolite will also be summarized. In 
addition to mean, standard deviation, median, minimum, and maximum, the AUC parameters 
and Cmax will be summarized by treatment group as geometric mean and coefficient of 
variation (ie, 100*SQRT( EXP(VAR) - 1 ) with VAR= the variance of the log-transformed 
values).   The summary of tmax will be as median, minimum, and maximum. Trough 
concentration will be summarized as mean, standard deviation, minimum, and maximum. 
10.4 
Safety Evaluations 
All safety analysis will be performed using the Safety analysis population and will be presented by 
group Adverse event terms will be coded using the MedDRA version 25 (2022) dictionary. 
All AEs will be presented in a by-subject listing, detailing the verbatim term given by the 
investigator, the preferred term (PT), system organ class (SOC), onset date and time, end date 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
and time, severity, outcome, relationship to study drug, action taken with study drug, other 
action taken, seriousness and criteria for seriousness. 
All safety and tolerability data collected in the study will be listed by participant. The 
continuous variables will be summarized using number of eligible subjects (N), mean, 
standard deviation, median, minimum, and maximum. Frequency counts and percentages will 
be reported for categorical data.  
A treatment emergent adverse event is defined as an AE beginning on or after Day 1 of the 
study.  The number of events and the number and percent of subjects experiencing adverse 
events will be presented for all treatment-emergent adverse events (TEAE), all treatment-
related TEAEs, all severe TEAEs (Grades 3 and 4), and all TEAEs leading to study 
discontinuation. Number and percent of subjects with TEAEs will also be shown by SOC and 
PT. 
Vital signs, ECG measurements, and clinical laboratory test results (including hematology, 
serum chemistry, coagulation, and urinalysis) will be summarized at each time point as mean, 
standard deviation, median, minimum, and maximum. The investigator’s assessments of 
ECG as normal or abnormal will be summarized as number and percentage of subjects. Also, 
the presence of heart murmur at each time point will be summarized as number and 
percentage of subjects. Every cardiovascular safety incident will be listed by timepoint with 
accompanying symptoms and with BP and HR measurements. 
The results of all safety-related data, including physical examinations findings, vital signs, 
ECG assessments, and clinical laboratory test results, will be presented in by-subject listings. 
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES 
All exceptions to the planned analyses as described herein will be clearly indicated and 
explained in the study report. 
12. HEADINGS 
Each page of the analysis will show the sponsor’s name, the investigational product, and the 
protocol number. Report tables will be embedded in the MS Word report document from 
SAS program output without change. The footer of each table will show the name of the SAS 
program module which generated it, the names of all data sets providing input data in the 
program and the date and time the table was generated. 
 
 


TB Alliance 
Protocol No. TBAJ-876-CL002                                                               14 December 2022 
TKL No. P1980322 
 
 
13. ARCHIVING AND RETENTION OF DOCUMENTS 
After finalization of the analysis, the following will be archived at TKL Research, Inc. and/or 
with the study sponsor: 
x SAP and any amendments 
x DMP and Database Specification 
x All SAS code used in the project for statistical analysis, report tables generation, and 
analysis data set creation 
x Tables, listings and figures as included in the clinical study report 
x SDTM and ADaM datasets 
x Relevant correspondence 
x Any other pertinent study document (ie, study protocol, investigator’s brochure, 
correspondence, study report, etc.). 
 


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TKL No. P1980322 
 
 
15. OUTLINE OF PROPOSED TABLES, FIGURES AND LISTINGS  
 
Summary Tables 
14.1.1 
Summary of Subject Disposition 
14.1.2 
Summary of Subject Demographics and Baseline Variables 
14.1.3 
Summary of Prior Medications 
14.1.4 
Summary of Concomitant Medications 
14.2.1.1 
Summary of Plasma Midazolam Concentrations (ng/mL) 
14.2.1.2 
Summary of Plasma Digoxin Concentrations (ng/mL) 
14.2.1.3 
Summary of Day 17 Plasma TBAJ-876 Concentrations (ng/mL) 
14.2.2 
Summary of Drug-Drug Interaction 
14.2.3.1 
Summary of Midazolam Pharmacokinetic Parameters 
14.2.3.2 
Summary of Digoxin Pharmacokinetic Parameters 
14.2.3.3 
Summary of Day 17 TBAJ-876 Pharmacokinetic Parameters 
14.3.1 
Summary of Treatment-Emergent Adverse Events 
14.3.2 
Summary of Physical Examinations Findings 
14.3.3 
Summary of Vital Signs 
14.3.4 
Summary of ECG Findings 
14.3.5.1 
Summary of Clinical Laboratory Test Results, Hematology and Coagulation 
14.3.5.2 
Summary of Clinical Laboratory Test Results, Differential Blood Count 
14.3.5.3 
Summary of Clinical Laboratory Test Results, Electrolytes and Renal Function 
14.3.5.4 
Summary of Clinical Laboratory Test Results, Liver Function 
14.3.5.5 
Summary of Clinical Laboratory Test Results, Other Serum Chemistry 
14.3.5.6 
Summary of Clinical Laboratory Test Results, Urinalysis, Part 1 
14.3.5.7 
Summary of Clinical Laboratory Test Results, Urinalysis, Part 2 
 


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TKL No. P1980322 
 
 
Figures 
14.2.1 
Mean Plasma Midazolam Concentration vs Time Post-dose 
14.2.2 
Mean Plasma 1-Hydroxymidazolam Concentration vs Time Post-dose 
14.2.3 
Mean Plasma Digoxin Concentration vs Time Post-dose 
14.2.4 
Mean Day 17 Plasma TBAJ-876 Concentration vs Time Post-dose 
14.2.5 
Mean Day 17 Plasma M2 Concentration vs Time Post-dose 
14.2.6 
Mean Day 17 Plasma M3 Concentration vs Time Post-dose 
14.3.1.1 
Individual Subjects Plasma Midazolam Concentration vs Time Post-dose, Linear Scale 
14.3.1.2 
Individual Subjects Plasma Midazolam Concentration vs Time Post-dose, Log-linear Scale 
14.3.2.1 
Individual Subjects Plasma 1-Hydroxymidazolam  Concentration vs Time Post-dose, Linear Scale 
14.3.2.2 
Individual Subjects Plasma 1-Hydroxymidazolam  Concentration vs Time Post-dose, Log-linear Scale 
14.3.3.1 
Individual Subjects Plasma Digoxin Concentration vs Time Post-dose, Linear Scale 
14.3.3.2 
Individual Subjects Plasma Digoxin Concentration vs Time Post-dose, Log-linear Scale 
14.3.4 
Individual Subjects  Day 17 Plasma TBAJ-876  Concentration vs Time Post-dose 
14.3.5 
Individual Subjects  Day 17 Plasma M2 Concentration vs Time Post-dose 
14.3.6 
Individual Subjects  Day 17 Plasma M3 Concentration vs Time Post-dose 
Listings 
16.1.7 
Subject Enrollment 
16.2.1.1 
Screen Failures 
16.2.1.2 
Subject Disposition 
16.2.2 
Protocol Deviations 
16.2.4.1 
Demographics and Baseline Characteristics 
16.2.4.2 
Prior and Concomitant Medication 
16.2.4.3 
Medical History 


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Protocol No. TBAJ-876-CL002 
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TKL No. P1980322 
 
 
16.2.5.1 
Plasma Midazolam Concentrations 
16.2.5.2 
Plasma 1-Hydroxymidazolam Concentrations 
16.2.5.3 
Plasma Digoxin Concentrations 
16.2.5.4 
Plasma TBAJ-876 Concentrations 
16.2.5.5 
Plasma M2 Concentrations 
16.2.5.6 
Plasma M3 Concentrations 
16.2.6.1 
Midazolam Pharmacokinetic Parameters 
16.2.6.2 
1-Hydroxymidazolam Pharmacokinetic Parameters 
16.2.6.3 
Digoxin Pharmacokinetic Parameters 
16.2.6.4 
TBAJ-876 Dosing 
16.2.6.5 
TBAJ-876 Day 17 Pharmacokinetic Parameters 
16.2.7.1 
Adverse Events 
16.2.7.2 
Serious Adverse Events and Adverse Events Leading to Study Discontinuation 
16.2.7.3 
Cardiovascular Adverse Events 
16.2.8.1 
Physical Examinations 
16.2.8.2 
Vital Signs Measurements 
16.2.8.3 
Electrocardiogram (ECG) Results 
16.2.8.4.1 
Clinical Laboratory Test Results, Hematology and Coagulation 
16.2.8.4.2 
Clinical Laboratory Test Results, Differential Blood Count 
16.2.8.4.3 
Clinical Laboratory Test Results, Electrolytes and Renal Function 
16.2.8.4.4 
Clinical Laboratory Test Results, Liver Function 
16.2.8.4.5 
Clinical Laboratory Test Results, Other Serum Chemistry 
16.2.8.4.6 
Clinical Laboratory Test Results, Urinalysis, Part 1 
16.2.8.4.7 
Clinical Laboratory Test Results, Urinalysis, Part 2 
16.2.8.4.8 
Laboratory Values Outside of Normal Range 
16.2.8.5 
Childbearing Potential and Serum Pregnancy Test Results 
16.2.9 
General Comments 


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 TB Alliance 
Page  1 of 1 
Protocol Number: TBAJ-876-CL002 
Table 14.1.1: Summary of Subject Disposition 
 
 
 
 
 
 
 
 
 
 
Number of Subjects Screened 
xx 
 
 
 
n (%) Enrolled 
xx (xx.x) 
 
 
 
n (%) Screen Failure 
xx (xx.x) 
 
 
 
 
 
 
Number Enrolled 
xx 
 
 
n (%) Completed Study 
xx (xx.x) 
 
 
n (%) Discontinued Study 
xx (xx.x) 
 
 
 
n (%) Adverse Event/Serious Adverse Event 
xx (xx.x) 
 
 
 
n (%) Important Protocol Deviation (eg, non-compliance) 
xx (xx.x) 
 
 
 
n (%) Investigator Judgment 
xx (xx.x) 
 
 
 
n (%) Lost to Follow-up 
xx (xx.x) 
 
 
        n (%) xxxxxxxxxxxx 
xx (xx.x) 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
[Programming Note: List reasons for discontinuation in descending order of frequency. Omit rows with zero counts.] 
 
 


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Protocol No. TBAJ-876-CL002 
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TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 2 
Protocol Number: TBAJ-876-CL002 
Table 14.1.2: Summary of Subject Demographics and Baseline Variables 
Safety population (N=xx) 
 
Parameter 
Statistic 
 
 
 
 
 
 
 
 
Age 
Mean (SD) 
xxx (xx.x) 
 
 
 
Median 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
 
 
 
 
 
 
 
Sex 
n (%) Male 
x (xx.x) 
 
 
 
n (%) Female 
x (xx.x) 
 
 
 
 
 
 
 
Race 
n (%) White 
x (xx.x) 
 
 
 
n (%) Black or African American 
x (xx.x) 
 
 
 
n (%) Asian 
x (xx.x) 
 
 
 
n (%) American Indian or Alaska Native 
x (xx.x) 
 
 
 
n (%) Native Hawaiian or Other Pacific Islander 
x (xx.x) 
 
 
 
 
 
 
 
Ethnicity 
n (%) Hispanic or Latino 
x (xx.x) 
 
 
 
n (%) Not Hispanic or Latino 
x (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects could select more than one race and are counted in each race selected. SD=Standard deviation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
[Programming Note: Omit rows with zero counts.] 
 
 


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Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
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Protocol Number: TBAJ-876-CL002 
Table 14.1.2: Summary of Subject Demographics and Baseline Variables 
Safety population (N=xx) 
 
Parameter 
Statistic 
 
 
 
 
 
 
 
 
Height (cm) 
Mean (SD) 
xxx (xx.x) 
 
 
 
Median 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
 
 
 
 
 
 
 
Weight (kg) 
Mean (SD) 
xx.x (xx.x) 
 
 
 
Median 
xx.x 
 
 
 
Minimum, maximum 
xx.x, xx.x 
 
 
 
 
 
 
 
BMI (kg/m^2) 
Mean (SD) 
xx.x (xx.x) 
 
 
 
Median 
xx.x 
 
 
 
Minimum, maximum 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


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14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of Y 
Protocol Number: TBAJ-876-CL002 
Table 14.1.3: Summary of Prior Medications 
Safety population (N=xx) 
 
 
 
 
 
 
 
 
 
Number (%) of Subjects with Any Prior Medication 
xx (xx.x) 
 
 
 
 
 
 
[ATC2] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 1] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 2] 
xx (xx.x) 
 
 
 
 
 
 
[ATC2] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 1] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 2] 
xx (xx.x) 
 
 
 
 
 
 
[ATC2] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 1] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 2] 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Medications that were continued into the study period are summarized as both prior and concomitant. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
[Programming Note: List ATC2 classes and preferred names in descending order of frequency] 
 
 


TB Alliance 
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Protocol No. TBAJ-876-CL002 
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TKL No. P1980322 
 
 
TB Alliance 
Page  X of Y 
Protocol Number: TBAJ-876-CL002 
Table 14.1.4: Summary of Concomitant Medications 
Safety population (N=xx) 
 
 
 
 
 
 
 
 
 
Number (%) of Subjects with Any Concomitant Medication 
xx (xx.x) 
 
 
 
 
 
 
[ATC2] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 1] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 2] 
xx (xx.x) 
 
 
 
 
 
 
[ATC2] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 1] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 2] 
xx (xx.x) 
 
 
 
 
 
 
[ATC2] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 1] 
xx (xx.x) 
 
 
 
[WHO Preferred Name 2] 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Medications that were continued into the study period are summarized as both prior and concomitant. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
[Programming Note: List ATC2 classes and preferred names in descending order of frequency] 
 
 


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14 December 2022 
TKL No. P1980322 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Table 14.2.1.1: Summary of Plasma Midazolam Concentrations (ng/mL) 
PK Population 
 
Time Point 
Statistic 
Midazolam 
1-Hydroxymidazolam 
 
Alone 
With TBAJ-876 
Alone 
With TBAJ-876 
 
 
 
 
 
 
 
 
 
[Pre-dose, 15 mins, 30 mins, 1 hr, 2 hrs, 
3 hrs, 4 hrs, 6 hrs, 8 hrs, 12 hrs, 24 hrs] 
n 
xx 
xx 
xx 
x 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


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Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Table 14.2.1.2: Summary of Plasma Digoxin Concentrations (ng/mL) 
PK Population 
 
Time Point 
Statistic 
Digoxin 
 
Alone 
With TBAJ-876 
 
 
 
 
 
 
 
[Pre-dose, 30 mins, 1 hr, 2 hrs, 3 hrs, 
4 hrs, 6 hrs, 8 hrs, 12 hrs, 24 hrs, 48 hrs, 
72 hrs, 96 hrs] 
n 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


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Protocol No. TBAJ-876-CL002 
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TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Table 14.2.1.3: Summary of Day 17 Plasma TBAJ-876 Concentrations (ng/mL) 
PK Population 
 
Time Point 
Statistic 
TBAJ-876 
M2 
M3 
 
 
 
 
 
 
 
 
 
[Pre-dose, 30 mins, 3 hrs, 4 hrs, 5 hrs, 
6 hrs, 7 hrs, 8 hrs, 12 hrs, 16 hrs, 20 hrs, 
24 hrs] 
n 
xx 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


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Protocol No. TBAJ-876-CL002 
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TKL No. P1980322 
 
 
TB Alliance 
Page  1 of 1 
Protocol Number: TBAJ-876-CL002 
Table 14.2.2: Summary of Drug-Drug Interaction 
PK Population  
 
 
Midazolam 
Digoxin 
 
 
 
 
 
 
 
 
 
 
 
 
 
AUC0-inf (ng.hr/mL) 
N=xx 
N=xx 
 
 
 
Least-squares geometric mean (with TBAJ-876 [T]) 
xxx 
xxx 
 
 
 
Least-squares geometric mean (alone [R]) 
xxx 
xxx 
 
 
 
Ratio of geometric means (T/R) 
x.xxx 
x.xxx 
 
 
 
90% 2-sided confidence interval 
[x.xxx, x.xxx] 
[x.xxx, x.xxx] 
 
 
 
 
 
 
 
 
Cmax (ng/mL) 
N=xx 
N=xx 
 
 
 
Least-squares geometric mean (with TBAJ-876 [T]) 
xxx 
xxx 
 
 
 
Least-squares geometric mean (alone [R]) 
xxx 
xxx 
 
 
 
Ratio of geometric means (T/R) 
x.xxx 
x.xxx 
 
 
 
90% 2-sided confidence interval 
[x.xxx, x.xxx] 
[x.xxx, x.xxx] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: All estimates are of least squares means using the mixed linear model analysis of variance with random effects of subject and fixed effects of treatment. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


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TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 2 
Protocol Number: TBAJ-876-CL002 
Table 14.2.3.1: Summary of Midazolam Pharmacokinetic Parameters 
PK Population 
 
Parameter 
Statistic 
Midazolam 
1-Hydroxymidazolam 
 
Alone 
With TBAJ-876 
Alone 
With TBAJ-876 
 
 
 
 
 
 
 
 
 
AUC0-last (ng.hr/mL) 
n 
xx 
xx 
xx 
x 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
AUC0-inf (ng.hr/mL) 
n 
xx 
xx 
xx 
x 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
Cmax (ng/mL) 
n 
xx 
xx 
xx 
x 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


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Protocol No. TBAJ-876-CL002 
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TKL No. P1980322 
 
 
TB Alliance 
Page 2 of 2 
Protocol Number: TBAJ-876-CL002 
Table 14.2.3.1: Summary of Midazolam Pharmacokinetic Parameters 
PK Population 
 
Parameter 
Statistic 
Midazolam 
1-Hydroxymidazolam 
 
Alone 
With TBAJ-876 
Alone 
With TBAJ-876 
 
 
 
 
 
 
 
 
 
Tmax (hr) 
n 
xx 
xx 
xx 
x 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
kel (/hr) 
n 
xx 
xx 
xx 
x 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
t1/2 (hr) 
n 
xx 
xx 
xx 
x 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
CL/F (L/hr) 
n 
xx 
xx 
xx 
x 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
VZ/F (L) 
n 
xx 
xx 
xx 
x 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 15 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 2 
Protocol Number: TBAJ-876-CL002 
Table 14.2.3.2: Summary of Digoxin Pharmacokinetic Parameters 
PK Population 
 
Parameter 
Statistic 
Digoxin 
 
Alone 
With TBAJ-876 
 
 
 
 
 
 
 
AUC0-last (ng.hr/mL) 
n 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
AUC0-inf (ng.hr/mL) 
n 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
Cmax (ng/mL) 
n 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
 
 
 
Geometric mean 
xxx 
xxx 
 
 
 
CV (%) 
xx.x 
xx.x 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 16 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page 2 of 2 
Protocol Number: TBAJ-876-CL002 
Table 14.2.3.2: Summary of Digoxin Pharmacokinetic Parameters 
PK Population 
 
Parameter 
Statistic 
Digoxin 
 
Alone 
With TBAJ-876 
 
 
 
 
 
 
 
Tmax (hr) 
n 
xx 
xx 
 
 
 
Median 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
kel (/hr) 
n 
xx 
xx 
 
 
 
Median 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
t1/2 (hr) 
n 
xx 
xx 
 
 
 
Median 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
CL/F (L/hr) 
n 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
VZ/F (L) 
n 
xx 
xx 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
Median 
xxx 
xxx 
 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
SD=Standard deviation, CV=Coefficient of variation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 17 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 1 
Protocol Number: TBAJ-876-CL002 
Table 14.2.3.3: Summary of Day 17 TBAJ-876 Pharmacokinetic Parameters 
PK Population 
 
Parameter 
 
TBAJ-876 
M2 
M3 
Sum of TBAJ-876  
and M3 
 
 
 
 
 
 
 
 
AUC0-24 (ng.hr/mL) 
n 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
Geometric mean 
xxx 
xxx 
xxx 
xxx 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
Cmax (ng/mL) 
n 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
Geometric mean 
xxx 
xxx 
xxx 
xxx 
 
 
CV (%) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
tmax (hr) 
n 
xx 
xx 
xx 
xx 
 
 
Median 
xxx 
xxx 
xxx 
xxx 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
Ctrough (ng/mL) 
n 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx 
xxx 
xxx 
xxx 
 
 
Minimum, maximum 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
SD=Standard deviation. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 18 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Table 14.3.1: Summary of Treatment-Emergent Adverse Events 
Safety Population (N=xx) 
 
 
 
 
 
 
 
 
 
 
 
All TEAEs 
Number of events 
xx 
 
 
 
n (%) of subjects 
xx (xx.x) 
 
 
 
 
 
 
 
Treatment-related TEAEs 
Number of events 
xx 
 
 
 
n (%) of subjects 
xx (xx.x) 
 
 
 
 
 
 
 
Severe TEAEs 
Number of events 
xx 
 
 
 
n (%) of subjects 
xx (xx.x) 
 
 
 
 
 
 
 
TEAEs leading to study discontinuation 
Number of events 
xx 
 
 
 
n (%) of subjects 
xx (xx.x) 
 
 
 
 
 
 
 
[SOC1] 
n (%) of subjects 
xx (xx.x) 
 
 
 
[PT1] 
 
xx (xx.x) 
 
 
 
[PT2] 
 
xx (xx.x) 
 
 
 
[PT3] 
 
xx (xx.x) 
 
 
 
 
 
 
 
[SOC2] 
 
xx (xx.x) 
 
 
 
[PT1] 
 
xx (xx.x) 
 
 
 
[PT2] 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TEAE=Treatment-emergent adverse event (with onset on or after Day 1). 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 19 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
[Note: Show 0 without percentage as shown.] 
 
 
TB Alliance 
Page  1 of 1 
Protocol Number: TBAJ-876-CL002 
Table 14.3.2: Summary of Physical Examinations Findings 
Safety Population 
 
 
n(%) Abnormal 
Presence of 
Heart 
Murmur 
Time Point 
N 
HEENT 
Neck 
Heart 
Resp 
Abd 
MS 
Neur 
Skin 
Other 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
xx 
x (xx.x) 
0 
0 
0 
0 
x (xx.x) 
0 
0 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
xx 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
xx 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
Day 3 
xx 
0 
x (xx.x) 
0 
0 
0 
0 
0 
0 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
Day 4 
xx 
0 
0 
0 
0 
0 
0 
0 
0 
0 
x (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
Day 5 
xx 
0 
0 
0 
0 
0 
0 
0 
x (xx.x) 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
Day 25/ET 
xx 
0 
0 
0 
0 
0 
0 
0 
0 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Resp=Respiratory, Abd=Abdomen, MS=Musculoskeletal, Neur=Neurological status. 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 20 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Table 14.3.3: Summary of Vital Signs 
Safety Population 
Time Point 
 
Supine 
Systolic BP 
(mmHg) 
Supine 
Diastolic BP 
(mmHg) 
Supine Heart 
Rate 
(bpm) 
Temp 
(C) 
Resp Rate 
(bpm) 
Pulse 
Oximetry (%) 
Supine 
Systolic BP 
(mmHg) 
Supine 
Diastolic BP 
(mmHg) 
Supine Heart 
Rate 
(bpm) 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
xx.x 
xxx 
xxx 
xxx 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
xx.x 
xxx 
xxx 
xxx 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
Day 1, Pre-dose 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
xx.x 
xxx 
xxx 
xxx 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xxx, xxx 
xxx, xxx 
xxx, xxx 
 
 
 
 
 
 
 
 
 
 
 
Day 1, 0.5 hrs 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
xx.x 
xxx 
xxx 
xxx 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xxx, xxx 
xxx, xxx 
xxx, xxx 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 21 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Table 14.3.4.1: Summary of ECG Findings 
Safety Population 
Time Point 
 
HR 
(bpm) 
PR 
(msec) 
QRS 
(msec) 
QT 
(msec) 
QTcF 
(msec) 
 
Investigator’s Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
 
Normal, n(%) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
 
Abnormal, n(%) 
xx (xx.x) 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
 
Normal, n(%) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
 
Abnormal, n(%) 
xx (xx.x) 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2, Pre-dose 
n 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
 
Normal, n(%) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
 
Abnormal, n(%) 
xx (xx.x) 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2, 0.5 hrs 
n 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
 
Normal, n(%) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
xxx 
xx.x 
xx.x 
 
Abnormal, n(%) 
xx (xx.x) 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
xxx, xxx 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 22 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
Global Alliance for TB Drug Development    
Page  X of  Y 
Protocol Number: TBI-876-CL-002 
Table 14.3.4.2: Summary of 12-Lead ECG Numeric Results 
Absolute Values and Change from Baseline by Treatment and Time Point 
Safety Population 
 
Group 1 
(N=XX) 
Group 2 
(N=XX) 
Overall 
(N=XX) 
[Tests Name (Units)] 
 
 
 
Baseline  
 
 
 
N 
XX 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX 
XX 
XX 
Minimum, Maximum 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
Day 1 Post-Dose [2] 
 
 
 
N 
XX 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX 
XX 
XX 
Minimum, Maximum 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
     Change from Baseline 
 
 
 
N 
XX 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (XX.X) 
Median 
XX 
XX 
XX 
Minimum, Maximum 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
<Continue for all other applicable study days> 
Note: Baseline is the last available measurement prior to the first dose of the study drug on Day 1. 
 
Generated on` XX/XX/XX:XXXX  by XXX / Uses: XXXX / Reference: Data Listing XXXX 
 
[Programming note: Summarize all ECG tests with continuous results, including ventricular rate, PR, QRS, QT, QTcF intervals. Page break 
between ECG tests.] 
 


TB Alliance 
Page 23 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
Global Alliance for TB Drug Development    
Page  X of  Y 
Protocol Number: TBI-876-CL-002 
Table 14.3.4.3: Summary of 12-Lead ECG Categorical Analysis 
QTcF 
Safety Population 
 
Group 1 
(N=XX) 
Group 2 
(N=XX) 
Overall 
(N=XX) 
QTcF (msec) 
 
 
 
Absolute Values [1] 
 
 
 
> 450 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
> 480 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
> 500 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Change from baseline [2] 
 
 
 
> 30 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
> 60 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Note: Baseline is the last available measurement prior to the first dose of the study drug on Day 1. 
 
[1] Subjects with QTcF absolute values > (450, 480 and 500 msec) at any post dosing time point are included. 
[2] Subjects with QTcF change from baseline values > (30 and 60 msec) at any post dosing time point are included. 
<Programming Note: Additional QTcF value categories may be added to aid data interpretation. 
 
Generated on  XX/XX/XX:XXXX  by XXX / Uses: XXXX / Reference: Data Listing XXXX 
 
 
 


TB Alliance 
Page 24 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
TB Alliance 
Page  1 of  3 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.1: Summary of Clinical Laboratory Test Results, Hematology and Coagulation 
Safety Population 
 
Time Point 
 
HCT 
(ratio) 
HGB 
(g/L) 
RBC 
(10^12/L) 
WBC 
(10^9/L) 
PLAT 
(10^9/L) 
RETI 
(ratio) 
aPTT2 
(sec) 
PT2 
(sec) 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.x (x.x) 
xxx (xx.x) 
.xxx (.xxx) 
xx (xx.x) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
x.xx, x.xx 
x.x, x.x 
xxx, xxx 
.xxx, .xxx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.x (x.x) 
xxx (xx.x) 
.xxx (.xxx) 
xx (xx.x) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
x.xx, x.xx 
x.x, x.x 
xxx, xxx 
.xxx, .xxx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.x (x.x) 
xxx (xx.x) 
.xxx (.xxx) 
xx (xx.x) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
 
Min, Max 
xxx, xxx 
xxx, xxx 
x.xx, x.xx 
x.x, x.x 
xxx, xxx 
.xxx, .xxx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Day 3 
Mean (SD) 
xxx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.x (x.x) 
xxx (xx.x) 
.xxx (.xxx) 
xx (xx.x) 
xx (xx.x) 
 
 
Median 
xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
etc 
Min, Max 
xxx, xxx 
xxx, xxx 
x.xx, x.xx 
x.x, x.x 
xxx, xxx 
.xxx, .xxx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
HCT = Hematocrit; HGB = Hemoglobin; RBC = Erythrocytes; WBC=Leukocytes; PLAT = Platelets, RETI=Reticulocytes, aPTT2=Activated partial thromboplastin time, 
PT2=Prothrombin time. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 25 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  1 of  3 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.2: Summary of Clinical Laboratory Test Results, Differential Blood Count 
Safety Population 
 
Time Point 
 
NEUT 
LYM 
MONO 
EOS 
BASO 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
 
Min, Max 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
 
Min, Max 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
 
Min, Max 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Day 3 
Mean (SD) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
etc 
Min, Max 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
NEUT = Neutrophils; LYM = Lymphocytes; MONO = Monocytes; EOS = Eosinophils; BASO = Basophils 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 26 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  1 of  3 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.3: Summary of Clinical Laboratory Test Results, Electrolytes and Renal Function 
Safety Population 
 
Time Point 
 
SODIUM 
(mmol/L) 
K 
(mmol/L) 
CL  
(mmol/L) 
BICARB 
(mmol/L) 
CA 
(mmol/L) 
MG 
(mmol/L) 
UREAN 
(mmol/L) 
CREAT 
(umol/L) 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
x.x (x.x) 
xxx (xx.x) 
xx (xx.x) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
xx (xx.x) 
 
 
Median 
xxx 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
 
Min, Max 
xxx, xxx 
x.x, x.x 
xxx, xxx 
xx, xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
x.x (x.x) 
xxx (xx.x) 
xx (xx.x) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
xx (xx.x) 
 
 
Median 
xxx 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
 
Min, Max 
xxx, xxx 
x.x, x.x 
xxx, xxx 
xx, xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xxx (xx.x) 
x.x (x.x) 
xxx (xx.x) 
xx (xx.x) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
xx (xx.x) 
 
 
Median 
xxx 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
 
Min, Max 
xxx, xxx 
x.x, x.x 
xxx, xxx 
xx, xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Day 3 
Mean (SD) 
xxx (xx.x) 
x.x (x.x) 
xxx (xx.x) 
xx (xx.x) 
x.x (x.x) 
x.xx (x.xx) 
x.x (x.x) 
xx (xx.x) 
 
 
Median 
xxx 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
etc 
Min, Max 
xxx, xxx 
x.x, x.x 
xxx, xxx 
xx, xx 
x.x, x.x 
x.xx, x.xx 
x.x, x.x 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
K=Potassium, CL=Chloride, BICARB=Bicarbonate, CA=Calcium, MG=Magnesium, UREAN=Urea nitrogen, CREAT=Creatinine 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
[Programming Note: For out of range results, use bold font and superscript L or H] 
 
 


TB Alliance 
Page 27 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  1 of  3 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.4: Summary of Clinical Laboratory Test Results, Liver Function 
Safety Population 
 
Time Point 
 
ALT 
(ukat/L) 
AST 
(ukat/L) 
ALP 
(ukat/L) 
TBILI 
(umol/L) 
DBILI 
(umol/L) 
IBILI 
(umol/L) 
LDH 
(ukat/L) 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
 
Min, Max 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
 
Min, Max 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
 
Min, Max 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Day 3 
Mean (SD) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.xx (x.xx) 
 
 
Median 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
etc 
Min, Max 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
x.x, x.x 
x.x, x.x 
x.x, x.x 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
ALT=Alanine transaminase, AST=Aspartate transaminase, ALP=Alkaline phosphatase, TBILI=Total bilirubin, DBILI=Direct bilirubin, IBILI=Indirect bilirubin, LDH=Lactate 
dehydrogenase. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 28 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  1 of  3 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.5: Summary of Clinical Laboratory Test Results, Other Serum Chemistry 
Safety Population 
 
Time Point 
 
TPROT 
(g/L) 
GLUC 
(mmol/L) 
ALB 
(g/L) 
URAC 
(umol/L) 
CPK 
(ukat/L) 
AMY 
(ukat/L) 
LIP 
(ukat/L) 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xx (xx.x) 
xxx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
 
 
Median 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
 
Min, Max 
xx, xx 
xxx, xxx 
xx, xx 
xxx, xxx 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xx (xx.x) 
xxx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
 
 
Median 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
 
Min, Max 
xx, xx 
xxx, xxx 
xx, xx 
xxx, xxx 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
Mean (SD) 
xx (xx.x) 
xxx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
 
 
Median 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
 
Min, Max 
xx, xx 
xxx, xxx 
xx, xx 
xxx, xxx 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
n 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
Day 3 
Mean (SD) 
xx (xx.x) 
xxx (xx.x) 
xx (xx.x) 
xxx (xx.x) 
x.xx (x.xx) 
x.xx (x.xx) 
x.xx (x.xx) 
 
 
Median 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
etc 
Min, Max 
xx, xx 
xxx, xxx 
xx, xx 
xxx, xxx 
x.xx, x.xx 
x.xx, x.xx 
x.xx, x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TPROT=Total protein, GLUC=Glucose, ALB=Albumin, URAC=Uric acid, CPK=Creatinine phosphokinase, AMY=Amylase, LIP=Lipase 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 29 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  1 of  2 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.6: Summary of Clinical Laboratory Test Results, Urinalysis, Part 1 
Safety Population 
 
Time Point 
 
pH 
SpG (g/mL) 
GLUC 
KET 
BILI 
CREAT 
SOD 
 
 
 
 
 
 
 
 
 
 
 
Screening 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Day -1 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Day 3 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Day 7 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
Day 20 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SpG=Specific gravity, GLUC=Glucose, KET=Ketones, BILI=Bilirubin, CREAT=Creatinine, SOD=Sodium. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
[Programming Note: For out of range results, use bold font and superscript A.] 
 
 


TB Alliance 
Page 30 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  1 of  2 
Protocol Number: TBAJ-876-CL002 
Table 14.3.5.7: Summary of Clinical Laboratory Test Results, Urinalysis, Part 2 
Safety Population 
 
Time Point 
 
PROT 
OCC 
NIT 
LEUK 
Microscopic Examination (if 
indicated) 
 
 
 
 
 
 
 
 
 
Screening 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Day -1 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Day 2 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Day 3 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Day 7 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Day 20 
n(%) Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
n (%) Abnormal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROT=Protein, OCC=Occult blood, NIT=Nitrite, LEUK=Leukocyte esterase. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 31 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 1 
Protocol Number: TBAJ-876-CL002 
 
Figure 14.2.1: Mean Plasma Midazolam Concentration vs Time Post-dose 
PK Population 
 
 
 
Note: Concentrations BLOQ are included as 0. 
 
Generated on ... by ... / Uses: ADPC / Reference: Table 14.2.1.2.1. 
Note: Use similar formats for all analytes and for individual subject plots. 
Plasma Concentration (ng/mL)
0
10
20
30
40
50
60
70
80
90
100
Time Post-dose (h)
0
2
4
6
8
10
12
14
16
18
20
22
24
Day 1 (alone)
Day 20 (with TBAJ-876)


TB Alliance 
Page 32 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 1 
Protocol Number: TBAJ-876-CL002 
 
Figure 14.2.3: Mean Plasma Digoxin Concentration vs Time Post-dose 
PK Population 
 
 
 
Note: Concentrations BLOQ are included as 0. 
 
Generated on ... by ... / Uses: ADPC / Reference: Table 14.2.1.2.1. 
 
Plasma Concentration (ng/mL)
0
10
20
30
40
50
60
70
80
90
100
Time Post-dose (h)
0
8
16
24
32
40
48
56
64
72
80
88
96
Day 2 (alone)
Day 21 (with TBAJ-876)


TB Alliance 
Page 33 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page 1 of 1 
Protocol Number: TBAJ-876-CL002 
 
Figure 14.2.4: Mean Day 17 Plasma TBAJ-876 Concentration vs Time Post-dose 
PK Population 
 
 
 
Note: Concentrations BLOQ are included as 0. 
 
Generated on ... by ... / Uses: ADPC / Reference: Table 14.2.1.2.1. 
 
Plasma Concentration (ng/mL)
0
10
20
30
40
50
60
70
80
90
100
Time Post-dose (h)
0
2
4
6
8
10
12
14
16
18
20
22
24


TB Alliance 
Page 34 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
[Programming Note: List all enrolled subjects in order of their date-time of enrollment.] 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.1.7: Subject Enrollment 
All Enrolled Subjects 
Subject 
Date of Informed Consent 
Satisfy All I/E Criteria? 
Date-Time of Enrollment 
Enrollment Number 
Group 
 
 
 
 
 
 
xxx 
xxxx-xx-xx 
xxx 
xxxx-xx-xxTxx:xx 
xxx 
1 
xxx 
xxxx-xx-xx 
xxx 
xxxx-xx-xxTxx:xx 
xxx 
1 
xxx 
xxxx-xx-xx 
xxx 
xxxx-xx-xxTxx:xx 
xxx 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX XX:XX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 35 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
[Programming Note: In Reason for Screen Failure, include list of inclusion criteria not met along with Primary Reason for Screen 
Failure and Comments (IECOMM).] 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.1.1: Screen Failures 
Subject 
Date of 
Informed 
Consent 
Date of 
Screening 
 
Sex 
Race 
Ethnicity 
Reason for Screen Failure 
 
 
 
 
 
 
 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx 
xxxx-xx-xx 
xxxxxxx 
xxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXXXXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 36 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
[Programming Note: Study completion status will include reason for discontinuation (DSDECOD and DSCMTS)] 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.1.2: Subject Disposition 
All Enrolled Subjects 
Subject 
Screening Date 
Date Enrolled 
Date of Last Visit 
Date of Last Contact 
Completion Status 
 
 
 
 
 
 
xxx 
xxxx-xx-xx (-xx) 
xxxx-xx-xx (1) 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx (-xx) 
xxxx-xx-xx (1) 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx (-xx) 
xxxx-xx-xx (1) 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx (-xx) 
xxxx-xx-xx (1) 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx (-xx) 
xxxx-xx-xx (1) 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxx 
xxx 
xxxx-xx-xx (-xx) 
xxxx-xx-xx (1) 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 37 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.2: Protocol Deviations 
All Enrolled Subjects 
Subject 
Category 
Date (Day) 
Protocol Deviation 
Protocol Deviation Type 
Action Taken 
 
 
 
 
 
 
xxx 
Major 
xxxx-xx-xx (x) 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
Major 
xxxx-xx-xx (x) 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
xxx 
Major 
xxxx-xx-xx (xx) 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 38 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
 
Listing 16.2.4.1: Demographics and Baseline Characteristics 
All Enrolled Subjects 
Subject 
Age 
Gender 
Race 
Ethnicity 
Weight (kg) 
Height (cm) 
BMI (kg/m2) 
Screening 
Day -1 
 
 
 
 
 
 
 
 
 
xxx 
xx 
Male 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xx.x 
xx.x 
xxx.x 
xx.x 
xxx 
xx 
Female 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xx.x 
xx.x 
xxx.x 
xx.x 
xxx 
xx 
Male 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xx.x 
xx.x 
xxx.x 
xx.x 
xxx 
xx 
Female 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xx.x 
xx.x 
xxx.x 
xx.x 
xxx 
xx 
Female 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xx.x 
xx.x 
xxx.x 
xx.x 
xxx 
xx 
Male 
xxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xx.x 
xx.x 
xxx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: BMI = Body Mass Index 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 39 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
 
Listing 16.2.4.2: Prior and Concomitant Medication 
Safety Population 
Subject 
Prior or 
Concomitant? 
WHO Preferred Term (Verbatim Term) /  
ATC Classification 
Indication / 
Dose Unit / Frequency / Route 
Start Date (Day)-Stop Date (Day)  
 
 
 
 
 
xxx 
Concomitant 
xxxxxxxxxxxxxx (xxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxx / 
xxxxx xxxx / xxxxxxxxxxxx / xxxxxxxxxxxxxx 
xxxx-xx-xx (xx) - 
xxxx-xx-xx (xx) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is shown only if it is on or after Day 1, or within 30 days prior to Day 1. 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 
 
[Programming Note: List medications in ascending order of start date for each subject.] 
 
 
 


TB Alliance 
Page 40 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.4.3: Medical History  
Safety Population 
Subject 
Diagnosis 
Start Date (Day)  
End Date (Day)  
Medication Taken Currently? 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxx 
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xx (xx) 
Ongoing 
xxx 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xx (xx) 
xxxx-xx-xx (xx) 
xxx 
 
 
 
 
 
Note: Study day is shown only if it is within 30 days prior to Day 1. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX/ Uses: XXXX 


TB Alliance 
Page 41 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.5.1: Plasma Midazolam Concentrations 
PK Population 
Subject 
Day 
Date-time of 
Dosing 
 
Pre-
dose 
15 
mins 
30 
mins 
1 hr 
2 hrs 
3 hrs 
4 hrs 
6 hrs 
8 hrs 
12 hrs 
24 hrs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 42 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.5.2: Plasma 1-Hydroxymidazolam Concentrations 
PK Population 
Subject 
Day 
Date-time of 
Dosing 
 
Pre-
dose 
15 
mins 
30 
mins 
1 hr 
2 hrs 
3 hrs 
4 hrs 
6 hrs 
8 hrs 
12 hrs 
24 hrs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 43 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.5.3: Plasma Digoxin Concentrations 
PK Population 
Subj 
Day 
Date-time of 
Dosing 
 
Pre-
dose 
30 
mins 
1 hr 
2 hrs 
3 hrs 
4 hrs 
6 hrs 
8 hrs 
12 
hrs 
24 
hrs 
48 
hrs 
72 
hrs 
96 
hrs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
2 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
21 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
2 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
21 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 44 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.5.4: Plasma TBAJ-876 Concentrations 
PK Population 
Subject 
Day 
Date-time of 
Dosing 
 
Pre-
dose 
30 
mins 
3 hrs 
4 hrs 
5 hrs 
6 hrs 
7 hrs 
8 hrs 
12 hrs 
16 hrs 
20 hrs 
24 
hrs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 45 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.5.5: Plasma M2 Concentrations 
PK Population 
Subject 
Day 
Date-time of 
Dosing 
 
Pre-
dose 
30 
mins 
3 hrs 
4 hrs 
5 hrs 
6 hrs 
7 hrs 
8 hrs 
12 hrs 
16 hrs 
20 hrs 
24 
hrs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 46 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.5.6: Plasma M3 Concentrations 
PK Population 
Subject 
Day 
Date-time of 
Dosing 
 
Pre-
dose 
30 
mins 
3 hrs 
4 hrs 
5 hrs 
6 hrs 
7 hrs 
8 hrs 
12 hrs 
16 hrs 
20 hrs 
24 
hrs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
17 
xxxx-xx-xxTxx:xx 
Sample Time 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
Concentration (ng/mL) 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 47 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.6.1: Midazolam Pharmacokinetic Parameters 
PK Population 
Subj 
Day 
Date-time of Dosing 
AUC0-last 
(ng.hr/mL) 
AUC0-inf 
(ng.hr/mL) 
Cmax 
(ng/mL) 
tmax 
(hr) 
kel 
(/hr) 
t1/2 
(hr) 
CL/F 
(L/hr) 
VZ/F 
(L) 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
20 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
20 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
20 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 48 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.6.2: 1-Hydroxymidazolam Pharmacokinetic Parameters 
PK Population 
Subj 
Day 
Date-time of Dosing 
AUC0-last 
(ng.hr/mL) 
AUC0-inf 
(ng.hr/mL) 
Cmax 
(ng/mL) 
tmax 
(hr) 
kel 
(/hr) 
t1/2 
(hr) 
CL/F 
(L/hr) 
VZ/F 
(L) 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
20 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
20 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
xxx 
1 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
20 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 49 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.6.3: Digoxin Pharmacokinetic Parameters 
PK Population 
Subj 
Day 
Date-time of Dosing 
AUC0-last 
(ng.hr/mL) 
AUC0-inf 
(ng.hr/mL) 
Cmax 
(ng/mL) 
tmax 
(hr) 
kel 
(/hr) 
t1/2 
(hr) 
CL/F 
(L/hr) 
VZ/F 
(L) 
 
 
 
 
 
 
 
 
 
 
 
xxx 
2 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
21 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
xxx 
2 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
21 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
xxx 
2 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
21 
xxxx-xx-xxTxx:xx 
xxxx 
xxxx 
xx.x 
x.xx 
x.xxxx 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 50 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.6.4: TBAJ-876 Dosing 
All Enrolled Subjects 
 
Time of Dosing (Day) 
Subj 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
22 
23 
24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xxx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
xx:xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 51 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.6.5: TBAJ-876 Day 17 Pharmacokinetic Parameters 
PK Population 
 
TBAJ-876 
M2 
M3 
Subj 
AUC0-24 
(ng.hr/mL) 
Cmax 
(ng/mL) 
tmax 
(hr) 
Ctrough 
(ng/mL) 
AUC0-24 
(ng.hr/mL) 
Cmax 
(ng/mL) 
tmax 
(hr) 
Ctrough 
(ng/mL) 
AUC0-24 
(ng.hr/mL) 
Cmax 
(ng/mL) 
tmax 
(hr) 
Ctrough 
(ng/mL) 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxx 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
xxxx 
xx.x 
x.xx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 52 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
 
Listing 16.2.7.1: Adverse Events 
Safety Population 
Subject 
MedDRA Preferred Term  
(Verbatim Term) /  
MedDRA SOC Term 
Start Date-Time (Day) - 
Stop Date-Time (Day) / 
Date-Time (Day) Reported 
TEAE? / 
Severity / 
Outcome / 
Relationship to Study Drug 
(Regimen*)  
Action Taken with Study Product / 
Other Action Taken /  
Serious? (Criteria Met) 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
xxxx-xx-xxTxx:xx (xx) / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx (xxxxxx) 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
Ongoing / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx (xxxxxx) 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
xxxx-xx-xxTxx:xx (xx) / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx (xxxxxx) 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
 
 
 
 
 
TEAE= Treatment-emergent adverse event (onset on or after Day 1); SOC=System organ class 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
*Note: For Relationship to Study Drug Regimen, show “Not related” if data show “Not related” for all study products. Otherwise, 
list degree of relationship and attributed regimen (TBAJ-876, midazolam, digoxin, TBAJ-876 plus midazolam, etc). 
 
 


TB Alliance 
Page 53 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
 
Listing 16.2.7.2: Serious Adverse Events and Adverse Events Leading to Study Discontinuation 
Safety Population 
Subject 
MedDRA Preferred Term  
(Verbatim Term) /  
MedDRA SOC Term 
Start Date-Time (Day) - 
Stop Date-Time (Day) / 
Date-Time (Day) Reported 
TEAE? / 
Severity / 
Outcome / 
Relationship to Study Drug 
Regimen 
Action Taken with Study Product / 
Other Action Taken /  
Serious? (Criteria Met) 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
xxxx-xx-xxTxx:xx (xx) / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
Ongoing / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) / 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
xxxx-xx-xxTxx:xx (xx) / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
 
 
 
 
 
TEAE= Treatment-emergent adverse event (onset on or after Day 1); SOC=System organ class 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
Note: For Relationship to Study Drug Regimen, show “Not related” if data show “Not related” for all study products. Otherwise, list 
degree of relationship and attributed regimen (TBAJ-876, midazolam, digoxin, TBAJ-876 plus midazolam, etc). 
 
 
 


TB Alliance 
Page 54 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
 
Listing 16.2.7.3: Cardiovascular Adverse Events 
Safety Population 
Subject 
MedDRA Preferred Term  
(Verbatim Term) /  
MedDRA SOC Term 
Start Date-Time (Day) - 
Stop Date-Time (Day) / 
Date-Time (Day) Reported 
TEAE? / 
Severity / 
Outcome / 
Relationship to Study 
Drug Regimen 
Action Taken with Study 
Product / 
Other Action Taken /  
Serious? (Criteria Met) 
Vital Signs Taken Closest to 
Cardiovascular Event:  
Systolic BP (mmHg)/Diastolic 
BP (mmHg) (Heart Rate 
(bpm)) 
 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) 
/ xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
xxxx-xx-xxTxx:xx (xx) / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
xxx/xx (xx) 
 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) 
/ xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
Ongoing / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
xxx/xx (xx) 
 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
(xxxxxxxxxxxxxxxxxxxxxxxxxxxx) 
/ xxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (xx) –  
xxxx-xx-xxTxx:xx (xx) / 
xxxx-xx-xxTxx:xx (xx) 
xxx / 
xxxxxxxx / 
xxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxx / 
xxxxxxxxxxxxxxxxxxxxxxx / 
xx 
xxx/xx (xx) 
 
 
 
 
 
TEAE= Treatment-emergent adverse event (onset on or after Day 1); SOC=System organ class 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
Note: For Relationship to Study Drug Regimen, show “Not related” if data show “Not related” for all study products. Otherwise, list 
degree of relationship and attributed regimen (TBAJ-876, midazolam, digoxin, TBAJ-876 plus midazolam, etc). 
 
 
 


TB Alliance 
Page 55 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.1: Physical Examinations 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
Body System 
Findings 
Presence of Heart Murmur 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-x) 
All systems 
Normal 
xxx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
All systems 
Normal 
xxx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
All systems 
Normal 
xxx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
 
 
 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xxx 
 
Day 4 
xxxx-xx-xxTxx:xx (x) 
All systems 
Normal 
xxx 
 
Day 5 
xxxx-xx-xxTxx:xx (x) 
All systems 
Normal 
xxx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (x) 
All systems 
Normal 
xxx 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-x) 
All systems 
Normal 
xxx 
 
etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Full physical examination includes HEENT, neck, heart, respiratory, abdomen, musculoskeletal, neurological status, skin, and other. Body systems were normal if not 
otherwise shown. 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 56 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.2: Vital Signs Measurements 
Safety Population  
Subj 
Time Point 
Date-Time (Day) 
Supine 
Systolic 
BP 
(mmHg) 
Supine 
Diastolic 
BP 
(mmHg) 
Supine 
Heart 
Rate 
(bpm) 
Temp 
(C) 
Resp Rate 
(bpm) 
Pulse 
Oximetry 
(%) 
Supine 
Systolic 
BP 
(mmHg) 
Supine 
Diastolic 
BP 
(mmHg) 
Supine 
Heart 
Rate 
(bpm) 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 1 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 6 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
Note: On Days 7 through 19, vital signs are taken 6 hours after dosing. Supine measurements are taken after at least 2 minutes in supine position, and standing measurements are 
taken after at least 1 minute standing. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 


TB Alliance 
Page 57 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.2: Vital Signs Measurements 
Safety Population 
Subj 
Time Point 
Date-Time (Day) 
Supine 
Systolic 
BP 
(mmHg) 
Supine 
Diastolic 
BP 
(mmHg) 
Supine 
Heart 
Rate 
(bpm) 
Temp 
(C) 
Resp Rate 
(bpm) 
Pulse 
Oximetry 
(%) 
Supine 
Systolic 
BP 
(mmHg) 
Supine 
Diastolic 
BP 
(mmHg) 
Supine 
Heart 
Rate 
(bpm) 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Day 6 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 8 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 9 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 10 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 11 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 12 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 13 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 14 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 15 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 16 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 17 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 18 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 19 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 20 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
Note: On Days 7 through 19, vital signs are taken 6 hours after dosing. Supine measurements are taken after at least 2 minutes in supine position, and standing measurements are 
taken after at least 1 minute standing. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 


TB Alliance 
Page 58 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.2: Vital Signs Measurements 
Safety Population 
Subj 
Time Point 
Date-Time (Day) 
Supine 
Systolic 
BP 
(mmHg) 
Supine 
Diastolic 
BP 
(mmHg) 
Supine 
Heart 
Rate 
(bpm) 
Temp 
(C) 
Resp Rate 
(bpm) 
Pulse 
Oximetry 
(%) 
Supine 
Systolic 
BP 
(mmHg) 
Supine 
Diastolic 
BP 
(mmHg) 
Supine 
Heart 
Rate 
(bpm) 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Day 20 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 21 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 24 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xx.x 
xx 
xx.x 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: On Days 7 through 19, vital signs are taken 6 hours after dosing. Supine measurements are taken after at least 2 minutes in supine position, and standing measurements are 
taken after at least 1 minute standing. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


TB Alliance 
Page 59 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.3: Electrocardiogram (ECG) Results 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
HR 
(bpm) 
PR 
(msec) 
QRS 
(msec) 
QT 
(msec) 
QTcF 
(msec) 
Investigator’s Assessment / Comments 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
Day 2 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
Day 7 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
Day 20 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
Day 21 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
Pre-dose 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
0.5 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
1 hr 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
2 hrs 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
6 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
12 hrs 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
Day 22 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
xxx 
xxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
HR=Heart rate, PR=PR interval, QRS=QRS duration, QT=QT interval, QTcF=Corrected QT interval; ET=Early termination. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
Note: Blank line after every subject. Repeat subject number at the top of each page. 
 


TB Alliance 
Page 60 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.1: Clinical Laboratory Test Results, Hematology and Coagulation 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
HCT 
(ratio) 
HGB 
(g/L) 
RBC 
(10^12/L) 
WBC 
(10^9/L) 
PLAT 
(10^9/L) 
RETI 
(ratio) 
aPTT2 
(sec) 
PT2 
(sec) 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
.xxx L 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
.xxx L 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
.xxx L 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
.xxx L 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
.xxx 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
.xxx L 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
.xxx L 
xxx 
x.xx 
x.x 
xxx 
.xxx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, ET=Early Termination. 
HCT = Hematocrit; HGB = Hemoglobin; RBC = Erythrocytes; WBC=Leukocytes; PLAT = Platelets, RETI=Reticulocytes, aPTT2=Activated partial thromboplastin time, 
PT2=Prothrombin time. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
[Programming Note: For out of range results, use bold font and superscript L or H as shown in the example] 
 
 


TB Alliance 
Page 61 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.2: Clinical Laboratory Test Results, Differential Blood Count 
Safety Population 
Subject Time Point 
Date-Time (Day) 
NEUT 
LYM 
MONO 
EOS 
BASO 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
(10^9/L) 
(Ratio) 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-xx) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
x.x 
x.xx 
x.x 
x.xx 
x.x L 
x.xx L 
x.x 
x.xx 
x.x 
x.xx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
x.x 
x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 H = High; L = Low; ET=Early Termination. 
NEUT = Neutrophils; LYM = Lymphocytes; MONO = Monocytes; EOS = Eosinophils; BASO = Basophils 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
[Programming Note: For out of range results, use bold font and superscript L or H as shown in the example] 
 
 


TB Alliance 
Page 62 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.3: Clinical Laboratory Test Results, Electrolytes and Renal Function 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
SODIUM 
(mmol/L) 
K 
(mmol/L) 
CL  
(mmol/L) 
BICARB 
(mmol/L) 
CA 
(mmol/L) 
MG 
(mmol/L) 
UREAN 
(mmol/L) 
CREAT 
(umol/L) 
 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-xx) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
xxx.x 
x.x 
xxx 
xx 
x.x 
x.xx 
x.x 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, ET=Early Termination. 
K=Potassium, CL=Chloride, BICARB=Bicarbonate, CA=Calcium, MG=Magnesium, UREAN=Urea nitrogen, CREAT=Creatinine 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
[Programming Note: For out of range results, use bold font and superscript L or H] 
 
 


TB Alliance 
Page 63 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.4: Clinical Laboratory Test Results, Liver Function 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
ALT 
(ukat/L) 
AST 
(ukat/L) 
ALP 
(ukat/L) 
TBILI 
(umol/L) 
DBILI 
(umol/L) 
IBILI 
(umol/L) 
LDH 
(ukat/L) 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-xx) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
x.xx 
x.xx 
x.xx 
x.x 
x.x 
x.x 
x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, ET=Early Termination. 
ALT=Alanine transaminase, AST=Aspartate transaminase, ALP=Alkaline phosphatase, TBILI=Total bilirubin, DBILI=Direct bilirubin, IBILI=Indirect bilirubin, LDH=Lactate 
dehydrogenase. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
[Programming Note: For out of range results, use bold font and superscript L or H] 
 
 


TB Alliance 
Page 64 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.5: Clinical Laboratory Test Results, Other Serum Chemistry 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
TPROT 
(g/L) 
GLUC 
(mmol/L) 
ALB 
(g/L) 
URAC 
(umol/L) 
CPK 
(ukat/L) 
AMY 
(ukat/L) 
LIP 
(ukat/L) 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-xx) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
xx 
xxx 
xx 
xxx 
x.xx 
x.xx 
x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H=High, L=Low, ET=Early Termination. 
TPROT=Total protein, GLUC=Glucose, ALB=Albumin, URAC=Uric acid, CPK=Creatinine phosphokinase, AMY=Amylase, LIP=Lipase 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
[Programming Note: For out of range results, use bold font and superscript L or H] 
 
 


TB Alliance 
Page 65 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.6: Clinical Laboratory Test Results, Urinalysis, Part 1 
Safety Population 
Subject 
Time 
Point 
Date-Time (Day) 
pH 
SpG (g/mL) 
GLUC 
KET 
BILI 
CREAT 
SOD 
 
 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-xx) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
x.x 
x.xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A=Abnormal, ET=Early Termination. 
SpG=Specific gravity, GLUC=Glucose, KET=Ketones, BILI=Bilirubin, CREAT=Creatinine, SOD=Sodium. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
[Programming Note: For out of range results, use bold font and superscript A.] 
 
 


TB Alliance 
Page 66 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.7: Clinical Laboratory Test Results, Urinalysis, Part 2 
Safety Population 
Subject 
Time Point 
Date-Time (Day) 
PROT 
OCC 
NIT 
LEUK 
Microscopic Examination (if indicated) 
 
 
 
 
 
 
 
 
xxx 
Screening 
xxxx-xx-xxTxx:xx (-xx) 
xxx 
xxx 
xxx 
xxx 
 
 
Day -1 
xxxx-xx-xxTxx:xx (-x) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 2 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 3 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 20 
xxxx-xx-xxTxx:xx (xx) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 21 
xxxx-xx-xxTxx:xx (xx) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 22 
xxxx-xx-xxTxx:xx (xx) 
xxx 
xxx 
xxx 
xxx 
 
 
Day 25/ET 
xxxx-xx-xxTxx:xx (xx) 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A=Abnormal, ET=Early Termination. 
PROT=Protein, OCC=Occult blood, NIT=Nitrite, LEUK=Leukocyte esterase. 
 
Generated on XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


TB Alliance 
Page 67 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
[Programming Note: Use SDTM terms for parameter and unit.] 
 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.4.8: Laboratory Values Outside of Normal Range 
Safety Population  
Subject 
Time Point 
Date-Time (Day) 
Panel 
Parameter (Unit) 
Reference Range 
Result 
Abnormality 
 
 
 
 
 
 
 
 
xxx 
Day -1 
xxxx-xx-xxTxx:xx (x) 
Chemistry 
xxxxxx (xx) 
xxxx, xxxx 
xx.xx 
Low 
 
Day 7 
xxxx-xx-xxTxx:xx (x) 
Chemistry 
xxxxxx (xx) 
xxxx, xxxx 
xx.xx 
Low 
 
 
 
 
 
 
 
 
xxx 
Day 22 
xxxx-xx-xxTxx:xx (-x) 
Hematology 
xxxxxx (xx) 
xxxx, xxxx 
xx.xx 
High 
 
 
 
 
 
 
 
 
 
 
Generated on XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 68 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
 
Note: Include serum FSH test result as shown for those subjects who present data. 
  
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.8.5: Childbearing Potential and Serum Pregnancy Test Results 
Safety Population 
Subject Childbearing Potential 
Screening 
Check-in (Day -1) 
Day 25 / Early Termination 
Date-Time 
Result 
Date-Time 
Result 
Date-Time 
Result 
 
 
 
 
 
 
 
 
xxx 
xxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxx 
xxxxxxxxxxxxxxxxxxxxx (FSH= 
xxx) 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxx 
xxxxxxxxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
xxxx-xx-xxTxx:xx (-x) 
xxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


TB Alliance 
Page 69 of 69 
Protocol No. TBAJ-876-CL002 
14 December 2022 
TKL No. P1980322 
 
 
TB Alliance 
Page  X of  Y 
Protocol Number: TBAJ-876-CL002 
Listing 16.2.9: General Comments 
Safety Population 
Subject 
Comment Reference 
Comment 
 
 
 
xxx 
xxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: CO