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

Phase 1

Completed

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

• Registration Number: NCT04493671
• Lead Sponsor: Global Alliance for TB Drug Development

Brief Summary

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

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 Timeline

• Study Start: 2020-06-08
• Study First Submitted: 2020-07-22
• Study First Submitted QC: 2020-07-27
• Study First Posted: 2020-07-30
• Primary Completion: 2022-06-16
• Study Completion: 2022-11-15
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-29
• Last Update Posted: 2025-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 137

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TBAJ-876 50mg SAD	TBAJ-876 suspension	Cohort 3 single dose of 50 mg TBAJ-876 (n=6) under fasted conditions
TBAJ-876 100mg fasted SAD	TBAJ-876 suspension	Cohort 4, single dose of 100 mg TBAJ-876 (n=9) under fasted conditions
TBAJ-876 10mg SAD	TBAJ-876 suspension	Cohort 1 single dose of 10 mg TBAJ-876 (n=6) under fasted conditions
TBAJ-876 100mg fed SAD	TBAJ-876 suspension	Cohort 4, dose of 100 mg TBAJ-876 (n=10) under fed conditions
TBAJ-876 200mg SAD	TBAJ-876 suspension	Cohort 5 single dose of 200 mg TBAJ-876 (n=6) under fasted conditions
TBAJ-876 400mg SAD	TBAJ-876 suspension	Cohort 6, single dose of 400 mg TBAJ-876) (n=6) under fasted conditions
TBAJ-876 800mg SAD	TBAJ-876 suspension	Cohort 7, Single dose of 800 mg TBAJ-876 (n=6) under fasted conditions
TBAJ-876 Placebo SAD	Placebo suspension	Single dose matching placebo for TBAJ-876 under fasted conditions (n=13)
TBAJ-876 25mg MAD	TBAJ-876 suspension	25 mg TBAJ-876 (n=9) for 14 days under fed conditions
TBAJ-876 75mg MAD	TBAJ-876 suspension	75 mg TBAJ-876) (n=9) for 14 days under fed conditions
TBAJ-876 200mg MAD	TBAJ-876 suspension	200 mg TBAJ-876 (n=9) for 14 days under fed conditions
TBAJ-876 Placebo MAD	Placebo suspension	Matching placebo for TBAJ-876 for 14 days under fed conditions (n=12)
TBAJ-876 1x100 mg rBA fasted	TBAJ-876 100 mg tablet	Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fasted conditions
TBAJ-876 1x100 mg rBA fed	TBAJ-876 100 mg tablet	Single dose TBAJ-876 of 100 mg (1 x 100 mg tablet) (n=10) under fed conditions
TBAJ-876 4x25 mg rBA fasted	TBAJ-876 25 mg tablet	Single dose TBAJ-876 of 100 mg (4 x 25 mg tablets) (n=10) under fasted conditions
TBAJ-876 25mg SAD	TBAJ-876 suspension	Cohort 2, Single dose of 25 mg TBAJ-876 (n=6) under fasted conditions

Primary Outcome Measures

Name	Time	Method
Number of Participants with Treatment-Related Adverse Events in Part 1, Single Ascending Dose	Day 1 to Day 28	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.
Number of Participants with Treatment-Related Adverse Events in Part 2, Multiple Ascending Dose	Day 1 to Day 133	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.
Number of Participants with Treatment-Related Adverse Events in Part 3, Relative Bioavailability Study	Day 1 to Day 21	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.

Secondary Outcome Measures

Name	Time	Method
AUCExtrap [Pharmacokinetic Analysis]	Days 1 - 28	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.
AUCinf [Pharmacokinetic Analysis]	Days 1 - 28	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.
AUClast [Pharmacokinetic Analysis]	Days 1 - 28	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.
AUCtau [Pharmacokinetic Analysis]	Days 1 - 28	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.
Cavg [Pharmacokinetic Analysis]	Days 1 - 28	PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Cavg is average concentration during the dosing interval.
Clast [Pharmacokinetic Analysis]	Days 1 - 28	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.
CL/F [Pharmacokinetic Analysis]	Days 1 - 28	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.
CLss/F [Pharmacokinetic Analysis]	Days 1 - 28	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.
Cmax [Pharmacokinetic Analysis]	Days 1 - 28	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.
RAUC [Pharmacokinetic Analysis]	Days 1 - 28	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.
RCmax [Pharmacokinetic Analysis]	Days 1 - 28	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.
Tlast [Pharmacokinetic Analysis]	Days 1 - 28	PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Tlast is time of the last quantifiable concentration.
Tmax [Pharmacokinetic Analysis]	Days 1 - 28	PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. Tmax is time of the maximum concentration.
T1/2 [Pharmacokinetic Analysis]	Days 1 - 28	PK parameters will be calculated from plasma concentrations of TBAJ-876 TBAJ-876, M2, and M3. T1/2 is the observed terminal half-life.
Vz/F [Pharmacokinetic Analysis]	Days 1 - 28	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.
λz [Pharmacokinetic Analysis]	Days 1 - 28	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.

Trial Locations

Locations (1)

Worldwide Clinical Trials; 🇺🇸 San Antonio, Texas, United States