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A Phase 1, Partially Blind, Placebo Controlled, Randomized, Combined Single Ascending Dose (SAD) with a Food Effect Cohort (Part 1), Multiple Ascending Dose (MAD) (Part 2), and Relative Bioavailability (rBA) (Part 3) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBAJ-876 in Healthy Adult Subjects
This study is a three-part, partially blinded, placebo controlled, combined single ascending dose with food-effect, multiple ascending dose study, and a single dose relative bioavailability study conducted at one study center in the United States.
Safety will be assessed throughout the study for all subjects. Safety assessments will include physical examinations, vital signs, serial ECGs, cardiac monitoring, adverse events (AEs), and clinical laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TBAJ-876 10mg SAD | Active Comparator | Cohort 1 single dose of 10 mg TBAJ-876 (n=6) under fasted conditions |
|
| TBAJ-876 25mg SAD | Active Comparator | Cohort 2, Single dose of 25 mg TBAJ-876 (n=6) under fasted conditions |
|
| TBAJ-876 50mg SAD | Active Comparator | Cohort 3 single dose of 50 mg TBAJ-876 (n=6) under fasted conditions |
|
| TBAJ-876 100mg fasted SAD | Active Comparator | Cohort 4, single dose of 100 mg TBAJ-876 (n=9) under fasted conditions |
|
| TBAJ-876 100mg fed SAD | Active Comparator | Cohort 4, dose of 100 mg TBAJ-876 (n=10) under fed conditions |
|
| TBAJ-876 200mg SAD | Active Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TBAJ-876 suspension | Drug | TBAJ-876 oral suspension, orally administered |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-Related Adverse Events in Part 1, Single Ascending Dose | Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug. | Day 1 to Day 28 |
| Number of Participants with Treatment-Related Adverse Events in Part 2, Multiple Ascending Dose | Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug. | Day 1 to Day 133 |
| Number of Participants with Treatment-Related Adverse Events in Part 3, Relative Bioavailability Study | Subjects will be monitored for any adverse events from the signing of the consent form until the end-of-study visit. The Investigator or a Sub-Investigator will assess its relationship to the study drug. | Day 1 to Day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| AUCExtrap [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUCExtrap is the percentage of AUCinf based on extrapolation. | Days 1 - 28 |
| AUCinf [Pharmacokinetic Analysis] |
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Key Inclusion Criteria:
All volunteers must satisfy the following criteria to be considered for study participation:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Antonio Lombardi, MD | Global Alliance for TB Drug Development | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Worldwide Clinical Trials | San Antonio | Texas | 78217 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39194204 | Result | Lombardi A, Pappas F, Nedelman J, Hickman D, Jaw-Tsai S, Olugbosi M, Bruinenberg P, Beumont M, Sun E. Pharmacokinetics and safety of TBAJ-876, a novel antimycobacterial diarylquinoline, in healthy subjects. Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0061324. doi: 10.1128/aac.00613-24. Epub 2024 Aug 28. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 3, 2021 | Nov 29, 2023 |
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Cohort 5 single dose of 200 mg TBAJ-876 (n=6) under fasted conditions
|
| TBAJ-876 400mg SAD | Active Comparator | Cohort 6, single dose of 400 mg TBAJ-876) (n=6) under fasted conditions |
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| TBAJ-876 800mg SAD | Active Comparator | Cohort 7, Single dose of 800 mg TBAJ-876 (n=6) under fasted conditions |
|
| TBAJ-876 Placebo SAD | Placebo Comparator | Single dose matching placebo for TBAJ-876 under fasted conditions (n=13) |
|
| TBAJ-876 25mg MAD | Active Comparator | 25 mg TBAJ-876 (n=9) for 14 days under fed conditions |
|
| TBAJ-876 75mg MAD | Active Comparator | 75 mg TBAJ-876) (n=9) for 14 days under fed conditions |
|
| TBAJ-876 200mg MAD | Active Comparator | 200 mg TBAJ-876 (n=9) for 14 days under fed conditions |
|
| TBAJ-876 Placebo MAD | Placebo Comparator | Matching placebo for TBAJ-876 for 14 days under fed conditions (n=12) |
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| TBAJ-876 1x100 mg rBA fasted | Active Comparator | Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fasted conditions |
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| TBAJ-876 1x100 mg rBA fed | Active Comparator | Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fed conditions |
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| TBAJ-876 4x25 mg rBA fasted | Active Comparator | Single dose TBAJ-876 of 100 mg (4 x 25 mg tablets) (n=10) under fasted conditions |
|
| Placebo suspension | Drug | Placebo for TBAJ-876 oral Suspension; orally administered |
|
| TBAJ-876 100 mg tablet | Drug | TBAJ-876 100 mg tablets, orally administered |
|
| TBAJ-876 25 mg tablet | Drug | TBAJ-876 25 mg tablets, orally administered |
|
PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUCinf is area under the concentration-time curve from time-zero extrapolated to infinity.
| Days 1 - 28 |
| AUClast [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUClast area under the concentration-time curve from time-zero to the time of the last quantifiable concentration; calculated using the linear trapezoidal rule. | Days 1 - 28 |
| AUCtau [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. AUCtau is area under the concentration-time curve during the dosing interval; calculated using the linear trapezoidal rule. | Days 1 - 28 |
| Cavg [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Cavg is average concentration during the dosing interval. | Days 1 - 28 |
| Clast [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Clast is the last quantifiable concentration determined directly from individual concentration-time data. | Days 1 - 28 |
| CL/F [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. CL/F is apparent total clearance after single administration. | Days 1 - 28 |
| CLss/F [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. CLss/F is apparent total clearance after multiple administration. | Days 1 - 28 |
| Cmax [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Cmax is maximum concentration, determined directly from individual concentration-time data. | Days 1 - 28 |
| RAUC [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. RAUC is accumulation factor during multiple dosing, based on AUCtau. | Days 1 - 28 |
| RCmax [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. RCmax is accumulation factor during multiple dosing, based on Cmax. | Days 1 - 28 |
| Tlast [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Tlast is time of the last quantifiable concentration. | Days 1 - 28 |
| Tmax [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Tmax is time of the maximum concentration. | Days 1 - 28 |
| T1/2 [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. T1/2 is the observed terminal half-life. | Days 1 - 28 |
| Vz/F [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Vz/F is apparent volume of distribution in the terminal phase. | Days 1 - 28 |
| λz [Pharmacokinetic Analysis] | PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. λz is the observed terminal rate constant; estimated by linear regression through at least 3 data points in the terminal phase of the log concentration-time profile. | Days 1 - 28 |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 25, 2022 | Nov 29, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D014397 | Tuberculosis, Pulmonary |
| D014376 | Tuberculosis |
| D018088 | Tuberculosis, Multidrug-Resistant |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
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| ID | Term |
|---|---|
| C000711567 | TBAJ-876 |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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