TuberculosisPhase 1NCT03758612
A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults
A Phase 1 study testing TBI-223 oral suspension, TBI-223 enteric capsule and TBI-223 SR Tablet Prototype 1 in people with Tuberculosis and Tuberculosis, Pulmonary, run by Global Alliance for TB Drug Development at 1 site in United States.
Trial summary
Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) with a Food Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults. Read more about this study
- Who is it for?
- Ages 19 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Tuberculosis, Pulmonary
- What is being tested?
- TBI-223 oral suspension, TBI-223 enteric capsule and TBI-223 SR Tablet Prototype 1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2019to 15 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Division of Microbiology and Infectious Diseases 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.
- QTcF interval >450 msec for males or >470 msec for females at screening, Day -1, or Day 1 (predose), or history of prolonged QT syndrome. For the triplicate 12-lead ECGs taken at screening and on Day -1, the average QTcF interval of the three 12-lead ECG recordings were used to determine qualification.
- Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that was causative of sudden death (such as known coronary artery disease, congestive heart failure, or terminal cancer).
- History of any of the following:
Show all 13Show fewer
- Serotonin syndrome
- Seizures or seizure disorders, other than childhood febrile seizures
- Brain surgery
- History of head injury in the last 5 years
- Any serious disorder of the nervous system particularly one that lowered the seizure threshold.
- Lactose intolerant.
- History of sensitivity or contraindication to use of linezolid, tedizolid, or any study investigational products
Trial locations and contacts
1 site in 1 country.
United States1 site
Worldwide Clinical Trials (WCT)
San Antonio, Texas, 78217
About this study
Official title: A Phase 1, Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) With a Food Effect Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adult Participants.
Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) with a Food Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults.
Read the detailed description
This study was a partially-blinded, placebo-controlled, randomized SAD study conducted at one study center. The primary objective of the study was to evaluate the safety and tolerability of single doses of TBI-223 oral suspension, TBI-223 oral enteric capsules, and TBI-223 tablet formulations in healthy adult subjects. The secondary objectives of the study were to determine the PK of TBI-223 and its metabolite M2 after single doses of TBI-223 oral suspension, TBI-223 oral enteric capsules, and TBI-223 tablet formulations in healthy adult subjects, and to compare the rate and extent of absorption of a single dose of TBI-223 oral suspension and TBI-223 tablet formulations when administered in healthy adult subjects either after a high-calorie, high-fat meal or in the fasting state.
Safety was assessed throughout the study for all subjects. Safety assessments included physical examinations, vital signs, serial ECGs, cardiac monitoring, adverse events (AEs), and clinical laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Being tested
- TBI-223 oral suspension, TBI-223 enteric capsule, TBI-223 SR Tablet Prototype 1, TBI-223 SR Tablet Prototype 2, TBI-223 SR Tablet Prototype 3
- Keywords
- TB, Tuberculosis, TBI-223, Pulmonary Tuberculosis
- Medical subject headings
- Tuberculosis, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TBI-223 oral suspensionDrug
TBI-223 oral suspension, orally administered.
TBI-223 enteric capsuleDrug
TBI-223 enteric capsules filled with 150 mg of TBI-223 powder, orally administered.
TBI-223 SR Tablet Prototype 1Drug
TBI-223 600 mg sustained-release (SR) tablet Prototype 1, orally administered.
TBI-223 SR Tablet Prototype 2Drug
TBI-223 600 mg SR tablet Prototype 2, orally administered.
TBI-223 SR Tablet Prototype 3Drug
TBI-223 900 mg SR tablet Prototype 3, orally administered.
TBI-223 IR TabletDrug
TBI-223 1000 mg immediate release (IR) tablet, orally administered
Placebo suspensionDrug
Placebo for TBI-223 oral Suspension; orally administered.
| Study group | Role | What they receive |
|---|---|---|
| TBI-223 50 mg | Active comparator | Cohort 1, single dose of TBI-223 50 mg dosed under fasted conditions Receives: Drug: TBI-223 oral suspension |
| TBI-223 100 mg | Active comparator | Cohort 2, single dose of TBI-223 100 mg dosed under fasted conditions Receives: Drug: TBI-223 oral suspension |
| TBI-223 300 mg | Active comparator | Cohort 3a, Period 1 - gave a single dose of TBI-223 300 mg oral suspension dosed under fasted conditions.
Cohort 3b, Period 2 - participants in cohort 3a were invited after a washout period to return for an additional single dose of TBI-223 300 mg enteric capsule dosed under fasted conditions Receives: Drug: TBI-223 oral suspension; Drug: TBI-223 enteric capsule |
| TBI-223 600 mg | Active comparator | Cohort 4, single dose of TBI-223 600 mg dosed under fasted conditions Receives: Drug: TBI-223 oral suspension |
| TBI-223 1200 mg | Active comparator | Cohort 5, Period 1, single dose of TBI-223 1200 mg dosed under fasted conditions.
Cohort 5, Period 2, participants were invited to return after a washout period to continue in period 2 and receive a single dose of TBI-223 1200 mg dosed under fed conditions Receives: Drug: TBI-223 oral suspension |
| TBI-223 2000 mg | Active comparator | Cohort 6, single dose of TBI-223 2000 mg dosed under fasted conditions Receives: Drug: TBI-223 oral suspension |
| TBI-223 2600 mg | Active comparator | Cohort 7, single dose of TBI-223 2600 mg dosed under fasted conditions Receives: Drug: TBI-223 oral suspension |
| TBI-223 placebo | Placebo comparator | Period 1 Single dose matching placebo for TBI-223 under fasted conditions for cohorts 1 to 7
Period 2 Placebo participants in cohort 5 were invited to return after a washout period and were administered a single dose matching placebo for TBI-223 1200mg under fed conditions Receives: Drug: Placebo suspension |
| TBI-223 3x600 mg SR-1 tablet | Active comparator | Cohort 8, arm 1 - Single dose TBI-223 of 1800 mg (3 x 600 mg) sustained release (SR) tablet formulation 1 under fed conditions Receives: Drug: TBI-223 SR Tablet Prototype 1 |
| TBI-223 3x600 mg SR-2 tablet | Active comparator | Cohort 8, arm 2 - Single dose TBI-223 of 1800 mg (3 x 600 mg) sustained release (SR) tablet formulation 2 under fed conditions Receives: Drug: TBI-223 SR Tablet Prototype 2 |
| TBI-223 2x900 mg SR-3 tablet | Active comparator | Cohort 8, arm 3 - Single dose TBI-223 of 1800 mg (2 x 900 mg) sustained release (SR) tablet formulation 3 under fed conditions Receives: Drug: TBI-223 SR Tablet Prototype 3 |
| TBI-223 2x1000 mg IR tablet | Active comparator | Cohort 8, arm 4 - Single dose TBI-223 of 2000 mg (2 x 1000 mg) immediate release (IR) tablet under fasted conditions
Cohort 9 - Participants from cohort 8 arm 4 were invited to return and were administered a single dose TBI-223 of 2000 mg (2 x 1000 mg) immediate release (IR) tablet under fed conditions Receives: Drug: TBI-223 IR 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
A treatment-related adverse event (AE) is defined for this study as any AE classified as possibly, probably or certainly related to the study drug. Adverse events (AEs) for participants who received at least one dose of study treatment were collected from the signing of informed consent till the end of study visit. An Investigator reviewed each AE collected and assessed its relationship to drug treatment based on all available information at the time of the completion of the study.
Measured: Day 1 - Day 11
Secondary outcomes (10)
Area Under the Plasma Concentration-time- Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf)
AUC0-inf will be calculated from plasma concentrations of TBI-223 AND M2 and calculated as AUC0-inf = AUC0-t + Clast/λz, where λz is the apparent terminal elimination rate constant calculated by linear regression of the terminal linear portion of the log concentration versus time curve
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
AUC0-t
AUC0-t will be calculated from plasma concentrations of TBI-223. Area under the plasma concentration-time curve from time-zero to the time of the last quantifiable concentration (Clast), as calculated by the linear trapezoidal rule.
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Maximum Plasma Concentration, Determined Directly From Individual Concentration-time- Data (Cmax)
Cmax will be calculated from plasma concentrations of TBI-223. Cmax is calculated as the maximum plasma concentration, determined directly from individual concentration-time- data
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Time of the Maximum Plasma Concentrations (Tmax)
Tmax will be calculated from plasma concentrations of TBI-223.
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
The Observed Terminal Elimination Half-life (t1/2)
T1/2 will be calculated from plasma concentrations of TBI-223 and calculated as T½ = ln(2)/λz
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 300 mg TBI-223 in Capsule to Oral Suspension Formulations
Geometric mean ratio of TBI-223 area under the (plasma concentration vs. time) curve and Cmax when administered as a Single 300 mg Dose of TBI-223 Capsule Formulation (Cohort 3 Repeat; Part 1; Test) and a Single 300 mg Dose of TBI-223 Oral Suspension (Cohort 3; Part 1; Reference).
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 1200 mg Oral Suspension Under Fasted to Fed Conditions
Geometric mean ratio of TBI-223 area under the (plasma concentration vs. time) curve and Cmax when administered as a Single 1200 mg Dose of TBI-223 Oral Suspension under Fed (Test) and Fasted (Reference) Conditions (Part 1; Cohort 5)
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 2000 mg of Immediate Release (IR) Tablets Under Fed to Fasted Conditions.
Geometric mean ratio of TBI-223 area under the (plasma concentration vs. time) curve and Cmax when administered as IR tablets, 2000 mg (2 x 1000 mg TBI-223 tablets) under Fed Conditions (Cohort 9; Test) and IR tablets, 2000 mg (2 x1000 mg TBI-223 tablets) under Fasted Conditions (Cohort 8; Reference)
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of TBI-223 1800 mg Sustained Release (SR) Tablets Under Fed Conditions to 2000 mg IR Tablets Under Fasted Conditions
Geometric mean ratio of TBI-223 area under the (plasma concentration vs. time) curve and Cmax when administered as SR (Prototypes 1, 2, and 3) under Fed Conditions (Cohort 8; Test) and IR, 2000 mg (2 x 1000 mg TBI-223 tablets) under Fasted Conditions (Cohort 8; Reference)
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 1800 mg SR Tablets (Prototypes 1, 2, 3,) to 2000 mg IR Tablets Under Fed Conditions
Geometric mean ratio of TBI-223 area under the (plasma concentration vs. time) curve and Cmax when administered as TBI-223 after 1800 mg SR tablets (Prototypes 1, 2, 3,) under Fed Conditions (Cohort 8; Test) and 2000 mg IR tablets (2 x 1000 mg TBI-223 tablets) under Fed Conditions (Cohort 8; Reference)
Measured: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2018
- Study start16 Jan 2019
- Primary completion15 Mar 2020
- Study completion15 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies 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
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jerry Nedelman, Study chair, Global Alliance for TB Drug Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03758612
- Sponsor's protocol ID
- TBI-223-CL-001
- Status last verified
- Oct 2024
- First submitted
- 20 Nov 2018
- Last updated
- 9 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lombardi A, Pappas F, Bruinenberg P, Nedelman J, Taneja R, Hickman D, Beumont M, Sun E. Pharmacokinetics, tolerability, and safety of TBI-223, a novel oxazolidinone, in healthy participants. Antimicrob Agents Chemother. 2025 Apr 2;69(4):e0154224. doi: 10.1128/aac.01542-24. Epub 2025 Mar 11.
PubMed 40067046
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) With a Food Effect Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adult Participants.
- ClinicalTrials.gov ID
- NCT03758612
- Acronym / sponsor ID
- TBI-223-CL-001
- Conditions
- Tuberculosis, Tuberculosis, Pulmonary
- Keywords
- TB, Tuberculosis, TBI-223, Pulmonary Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Global Alliance for TB Drug DevelopmentUniversity, hospital or other
- Study start
- 16 Jan 2019 (actual)
- Primary completion
- 15 Mar 2020 (actual)
- Study completion
- 15 Mar 2020 (actual)
- First posted
- 29 Nov 2018 (actual)
- Results
- Posted 9 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Partially-Blinded, Placebo-Controlled, Randomized, Single Ascending Dose (SAD) with a Food Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults.
Detailed description
This study was a partially-blinded, placebo-controlled, randomized SAD study conducted at one study center. The primary objective of the study was to evaluate the safety and tolerability of single doses of TBI-223 oral suspension, TBI-223 oral enteric capsules, and TBI-223 tablet formulations in healthy adult subjects. The secondary objectives of the study were to determine the PK of TBI-223 and its metabolite M2 after single doses of TBI-223 oral suspension, TBI-223 oral enteric capsules, and TBI-223 tablet formulations in healthy adult subjects, and to compare the rate and extent of absorption of a single dose of TBI-223 oral suspension and TBI-223 tablet formulations when administered in healthy adult subjects either after a high-calorie, high-fat meal or in the fasting state.
Safety was assessed throughout the study for all subjects. Safety assessments included physical examinations, vital signs, serial ECGs, cardiac monitoring, adverse events (AEs), and clinical laboratory tests (including hematology, serum chemistry, coagulation, and urinalysis).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| TBI-223 50 mg | Active comparator | Drug: TBI-223 oral suspensionCohort 1, single dose of TBI-223 50 mg dosed under fasted conditions |
| TBI-223 100 mg | Active comparator | Drug: TBI-223 oral suspensionCohort 2, single dose of TBI-223 100 mg dosed under fasted conditions |
| TBI-223 300 mg | Active comparator | Drug: TBI-223 oral suspension, Drug: TBI-223 enteric capsuleCohort 3a, Period 1 - gave a single dose of TBI-223 300 mg oral suspension dosed under fasted conditions. Cohort 3b, Period 2 - participants in cohort 3a were invited after a washout period to return for an additional single dose of TBI-223 300 mg enteric capsule dosed under fasted conditions |
| TBI-223 600 mg | Active comparator | Drug: TBI-223 oral suspensionCohort 4, single dose of TBI-223 600 mg dosed under fasted conditions |
| TBI-223 1200 mg | Active comparator | Drug: TBI-223 oral suspensionCohort 5, Period 1, single dose of TBI-223 1200 mg dosed under fasted conditions. Cohort 5, Period 2, participants were invited to return after a washout period to continue in period 2 and receive a single dose of TBI-223 1200 mg dosed under fed conditions |
| TBI-223 2000 mg | Active comparator | Drug: TBI-223 oral suspensionCohort 6, single dose of TBI-223 2000 mg dosed under fasted conditions |
| TBI-223 2600 mg | Active comparator | Drug: TBI-223 oral suspensionCohort 7, single dose of TBI-223 2600 mg dosed under fasted conditions |
| TBI-223 placebo | Placebo comparator | Drug: Placebo suspensionPeriod 1 Single dose matching placebo for TBI-223 under fasted conditions for cohorts 1 to 7 Period 2 Placebo participants in cohort 5 were invited to return after a washout period and were administered a single dose matching placebo for TBI-223 1200mg under fed conditions |
| TBI-223 3x600 mg SR-1 tablet | Active comparator | Drug: TBI-223 SR Tablet Prototype 1Cohort 8, arm 1 - Single dose TBI-223 of 1800 mg (3 x 600 mg) sustained release (SR) tablet formulation 1 under fed conditions |
| TBI-223 3x600 mg SR-2 tablet | Active comparator | Drug: TBI-223 SR Tablet Prototype 2Cohort 8, arm 2 - Single dose TBI-223 of 1800 mg (3 x 600 mg) sustained release (SR) tablet formulation 2 under fed conditions |
| TBI-223 2x900 mg SR-3 tablet | Active comparator | Drug: TBI-223 SR Tablet Prototype 3Cohort 8, arm 3 - Single dose TBI-223 of 1800 mg (2 x 900 mg) sustained release (SR) tablet formulation 3 under fed conditions |
| TBI-223 2x1000 mg IR tablet | Active comparator | Drug: TBI-223 IR TabletCohort 8, arm 4 - Single dose TBI-223 of 2000 mg (2 x 1000 mg) immediate release (IR) tablet under fasted conditions Cohort 9 - Participants from cohort 8 arm 4 were invited to return and were administered a single dose TBI-223 of 2000 mg (2 x 1000 mg) immediate release (IR) tablet under fed conditions |
Who may qualify
- Ages
- 19 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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 Division of Microbiology and Infectious Diseases 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.
Key exclusion criteria (13 listed)
- 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.
- QTcF interval >450 msec for males or >470 msec for females at screening, Day -1, or Day 1 (predose), or history of prolonged QT syndrome. For the triplicate 12-lead ECGs taken at screening and on Day -1, the average QTcF interval of the three 12-lead ECG recordings were used to determine qualification.
- Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that was causative of sudden death (such as known coronary artery disease, congestive heart failure, or terminal cancer).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TBI-223 oral suspensionTBI-223 oral suspension, orally administered. | Drug | TBI-223 100 mg, TBI-223 1200 mg, TBI-223 2000 mg, TBI-223 2600 mg, TBI-223 300 mg, TBI-223 50 mg, TBI-223 600 mg |
| TBI-223 enteric capsuleTBI-223 enteric capsules filled with 150 mg of TBI-223 powder, orally administered. | Drug | TBI-223 300 mg |
| TBI-223 SR Tablet Prototype 1TBI-223 600 mg sustained-release (SR) tablet Prototype 1, orally administered. | Drug | TBI-223 3x600 mg SR-1 tablet |
| TBI-223 SR Tablet Prototype 2TBI-223 600 mg SR tablet Prototype 2, orally administered. | Drug | TBI-223 3x600 mg SR-2 tablet |
| TBI-223 SR Tablet Prototype 3TBI-223 900 mg SR tablet Prototype 3, orally administered. | Drug | TBI-223 2x900 mg SR-3 tablet |
| TBI-223 IR TabletTBI-223 1000 mg immediate release (IR) tablet, orally administered | Drug | TBI-223 2x1000 mg IR tablet |
| Placebo suspensionPlacebo for TBI-223 oral Suspension; orally administered. | Drug | TBI-223 placebo |
Primary outcome
Number of Participants With Treatment-related Adverse Events
Time frame: Day 1 - Day 11
A treatment-related adverse event (AE) is defined for this study as any AE classified as possibly, probably or certainly related to the study drug. Adverse events (AEs) for participants who received at least one dose of study treatment were collected from the signing of informed consent till the end of study visit. An Investigator reviewed each AE collected and assessed its relationship to drug treatment based on all available information at the time of the completion of the study.
10 secondary outcomes
Area Under the Plasma Concentration-time- Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf)
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
AUC0-t
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Maximum Plasma Concentration, Determined Directly From Individual Concentration-time- Data (Cmax)
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Time of the Maximum Plasma Concentrations (Tmax)
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
The Observed Terminal Elimination Half-life (t1/2)
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 300 mg TBI-223 in Capsule to Oral Suspension Formulations
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 1200 mg Oral Suspension Under Fasted to Fed Conditions
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 2000 mg of Immediate Release (IR) Tablets Under Fed to Fasted Conditions.
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of TBI-223 1800 mg Sustained Release (SR) Tablets Under Fed Conditions to 2000 mg IR Tablets Under Fasted Conditions
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Geometric Mean Ratio and 90% Confidence Interval (CI) of Cmax, AUC0-t and AUC 0-inf of 1800 mg SR Tablets (Prototypes 1, 2, 3,) to 2000 mg IR Tablets Under Fed Conditions
Time frame: predose (0 hour) and at 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24, 30, 36, 42, 48, and 72 hours after administration of the investigational product
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40067046Lombardi A, Pappas F, Bruinenberg P, Nedelman J, Taneja R, Hickman D, Beumont M, Sun E. Pharmacokinetics, tolerability, and safety of TBI-223, a novel oxazolidinone, in healthy participants. Antimicrob Agents Chemother. 2025 Apr 2;69(4):e0154224. doi: 10.1128/aac.01542-24. Epub 2025 Mar 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jerry Nedelman study chair
Global Alliance for TB Drug Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TBI-223 oral suspension, TBI-223 enteric capsule and TBI-223 SR Tablet Prototype 1 in people with Tuberculosis and Tuberculosis, Pulmonary, run by Global Alliance for TB Drug Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Adverse Events (time frame: Day 1 - Day 11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03758612, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.