Pulmonary DiseasePhase 1NCT04493671
Evaluate Safety, Tolerability, PK of TBAJ-876 in Healthy Adults
A Phase 1 study testing TBAJ-876 suspension, TBAJ-876 100 mg tablet and TBAJ-876 25 mg tablet in people with Pulmonary Disease and Tuberculosis, Pulmonary, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 19 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Tuberculosis, Pulmonary, Tuberculosis
- What is being tested?
- TBAJ-876 suspension, TBAJ-876 100 mg tablet and TBAJ-876 25 mg tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 137 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2020to 15 Nov 2022
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All volunteers must satisfy the following criteria to be considered for study participation:
- Is a healthy adult male or female, 19 to 50 years of age (inclusive) at the time of screening.
- Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 kg.
- 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.
- Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing.
- 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.
Who cannot join
- 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.
- Any presence of musculoskeletal toxicity (severe tenderness with marked impairment of activity, or frank necrosis).
- Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or HIV at screening.
- 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).
- If assigned to the fasted/fed cohort, is lactose intolerant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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).
- Conditions
- Pulmonary Disease, Tuberculosis, Pulmonary, Tuberculosis, Multi Drug Resistant Tuberculosis, Drug Sensitive Tuberculosis, Drug-resistant Tuberculosis
- Being tested
- TBAJ-876 suspension, Placebo suspension, TBAJ-876 100 mg tablet, TBAJ-876 25 mg tablet
- Keywords
- TBAJ-876, Diarylquinoline, DARQ
- Medical subject headings
- Lung Diseases, Tuberculosis, Pulmonary, Tuberculosis, Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TBAJ-876 suspensionDrug
TBAJ-876 oral suspension, orally administered
Placebo suspensionDrug
Placebo for TBAJ-876 oral Suspension; orally administered
TBAJ-876 100 mg tabletDrug
TBAJ-876 100 mg tablets, orally administered
TBAJ-876 25 mg tabletDrug
TBAJ-876 25 mg tablets, orally administered
| Study group | Role | What they receive |
|---|---|---|
| TBAJ-876 10mg SAD | Active comparator | Cohort 1 single dose of 10 mg TBAJ-876 (n=6) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 25mg SAD | Active comparator | Cohort 2, Single dose of 25 mg TBAJ-876 (n=6) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 50mg SAD | Active comparator | Cohort 3 single dose of 50 mg TBAJ-876 (n=6) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 100mg fasted SAD | Active comparator | Cohort 4, single dose of 100 mg TBAJ-876 (n=9) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 100mg fed SAD | Active comparator | Cohort 4, dose of 100 mg TBAJ-876 (n=10) under fed conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 200mg SAD | Active comparator | Cohort 5 single dose of 200 mg TBAJ-876 (n=6) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 400mg SAD | Active comparator | Cohort 6, single dose of 400 mg TBAJ-876) (n=6) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 800mg SAD | Active comparator | Cohort 7, Single dose of 800 mg TBAJ-876 (n=6) under fasted conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 Placebo SAD | Placebo comparator | Single dose matching placebo for TBAJ-876 under fasted conditions (n=13) Receives: Drug: Placebo suspension |
| TBAJ-876 25mg MAD | Active comparator | 25 mg TBAJ-876 (n=9) for 14 days under fed conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 75mg MAD | Active comparator | 75 mg TBAJ-876) (n=9) for 14 days under fed conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 200mg MAD | Active comparator | 200 mg TBAJ-876 (n=9) for 14 days under fed conditions Receives: Drug: TBAJ-876 suspension |
| TBAJ-876 Placebo MAD | Placebo comparator | Matching placebo for TBAJ-876 for 14 days under fed conditions (n=12) Receives: Drug: Placebo suspension |
| 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 Receives: Drug: TBAJ-876 100 mg tablet |
| 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 Receives: Drug: TBAJ-876 100 mg tablet |
| 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 Receives: Drug: TBAJ-876 25 mg tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Day 21
Secondary outcomes (16)
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.
Measured: Days 1 - 28
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Days 1 - 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2020
- Study start8 Jun 2020
- Primary completion16 Jun 2022
- Study completion15 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonio Lombardi, MD, Study chair, Global Alliance for TB Drug Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04493671
- Sponsor's protocol ID
- TBAJ-876-CL-001
- Status last verified
- May 2025
- First submitted
- 22 Jul 2020
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 39194204