Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults

A Phase 1, Partially Blind, Placebo Controlled, Randomized, Combined Single Ascending Dose With a Food Effect Cohort, Multiple Ascending Dose, and Relative Bioavailability Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBAJ-876 in Healthy Adult Subjects

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

Study Overview

• Status: Completed
• Conditions: Tuberculosis; Tuberculosis, Pulmonary; Pulmonary Disease; Multi Drug Resistant Tuberculosis; Drug Sensitive Tuberculosis; Drug-resistant Tuberculosis; Mycobacterium Tuberculosis Infection
• Intervention / Treatment: Drug: TBAJ-876 suspension; Drug: Placebo suspension; Drug: TBAJ-876 100 mg tablet; Drug: TBAJ-876 25 mg tablet

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

All volunteers must satisfy the following criteria to be considered for study participation:

1. Is a healthy adult male or female, 19 to 50 years of age (inclusive) at the time of screening.
2. Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 kg.
3. Is medically healthy with no clinically significant screening results (e.g., laboratory profiles normal or up to Grade 1 per DMID Toxicity Tables), as deemed by the Investigator.
4. Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing.
5. If assigned to receive study drug under fed conditions, is willing and able to consume the entire high-calorie, high-fat breakfast meal in the timeframe required.

Key Exclusion Criteria:

1. History or presence of clinically significant cardiovascular (heart murmur), pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
2. Any presence of musculoskeletal toxicity (severe tenderness with marked impairment of activity, or frank necrosis).
3. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV at screening.
4. Current or history of prolonged QT syndrome15. 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).
5. If assigned to the fasted/fed cohort, is lactose intolerant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TBAJ-876 10mg SAD; Cohort 1 single dose of 10 mg TBAJ-876 (n=6) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 25mg SAD; Cohort 2, Single dose of 25 mg TBAJ-876 (n=6) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 50mg SAD; Cohort 3 single dose of 50 mg TBAJ-876 (n=6) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 100mg fasted SAD; Cohort 4, single dose of 100 mg TBAJ-876 (n=9) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 100mg fed SAD; Cohort 4, dose of 100 mg TBAJ-876 (n=10) under fed conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 200mg SAD; Cohort 5 single dose of 200 mg TBAJ-876 (n=6) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 400mg SAD; Cohort 6, single dose of 400 mg TBAJ-876) (n=6) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 800mg SAD; Cohort 7, Single dose of 800 mg TBAJ-876 (n=6) under fasted conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Placebo Comparator: TBAJ-876 Placebo SAD; Single dose matching placebo for TBAJ-876 under fasted conditions (n=13)	Drug: Placebo suspension; Placebo for TBAJ-876 oral Suspension; orally administered
Active Comparator: TBAJ-876 25mg MAD; 25 mg TBAJ-876 (n=9) for 14 days under fed conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 75mg MAD; 75 mg TBAJ-876) (n=9) for 14 days under fed conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Active Comparator: TBAJ-876 200mg MAD; 200 mg TBAJ-876 (n=9) for 14 days under fed conditions	Drug: TBAJ-876 suspension; TBAJ-876 oral suspension, orally administered
Placebo Comparator: TBAJ-876 Placebo MAD; Matching placebo for TBAJ-876 for 14 days under fed conditions (n=12)	Drug: Placebo suspension; Placebo for TBAJ-876 oral Suspension; orally administered
Active Comparator: TBAJ-876 1x100 mg rBA fasted; Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fasted conditions	Drug: TBAJ-876 100 mg tablet; TBAJ-876 100 mg tablets, orally administered
Active Comparator: TBAJ-876 1x100 mg rBA fed; Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fed conditions	Drug: TBAJ-876 100 mg tablet; TBAJ-876 100 mg tablets, orally administered
Active Comparator: TBAJ-876 4x25 mg rBA fasted; Single dose TBAJ-876 of 100 mg (4 x 25 mg tablets) (n=10) under fasted conditions	Drug: TBAJ-876 25 mg tablet; TBAJ-876 25 mg tablets, orally administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf [Pharmacokinetic Analysis]	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
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

Collaborators and Investigators

• Sponsor: Global Alliance for TB Drug Development
• Investigators: Study Chair: Antonio Lombardi, MD, Global Alliance for TB Drug Development

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): June 16, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 30, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: TBAJ-876; Diarylquinoline; DARQ
• Additional Relevant MeSH Terms: Latent Infection; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Latent Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant
• Other Study ID Numbers: TBAJ-876-CL-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No