A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults
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.
1 other identifier
interventional
86
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 20, 2018
CompletedFirst Posted
Study publicly available on registry
November 29, 2018
CompletedStudy Start
First participant enrolled
January 16, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 15, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 15, 2020
CompletedResults Posted
Study results publicly available
December 9, 2024
CompletedDecember 9, 2024
October 1, 2024
1.2 years
November 20, 2018
December 22, 2023
October 22, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Day 1 - Day 11
Secondary Outcomes (10)
Area Under the Plasma Concentration-time- Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf)
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
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)
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)
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)
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
- +5 more secondary outcomes
Study Arms (12)
TBI-223 50 mg
ACTIVE COMPARATORCohort 1, single dose of TBI-223 50 mg dosed under fasted conditions
TBI-223 100 mg
ACTIVE COMPARATORCohort 2, single dose of TBI-223 100 mg dosed under fasted conditions
TBI-223 300 mg
ACTIVE COMPARATORCohort 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 COMPARATORCohort 4, single dose of TBI-223 600 mg dosed under fasted conditions
TBI-223 1200 mg
ACTIVE COMPARATORCohort 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 COMPARATORCohort 6, single dose of TBI-223 2000 mg dosed under fasted conditions
TBI-223 2600 mg
ACTIVE COMPARATORCohort 7, single dose of TBI-223 2600 mg dosed under fasted conditions
TBI-223 placebo
PLACEBO COMPARATORPeriod 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 COMPARATORCohort 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 COMPARATORCohort 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 COMPARATORCohort 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 COMPARATORCohort 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
Interventions
TBI-223 oral suspension, orally administered.
TBI-223 enteric capsules filled with 150 mg of TBI-223 powder, orally administered.
TBI-223 600 mg sustained-release (SR) tablet Prototype 1, orally administered.
TBI-223 600 mg SR tablet Prototype 2, orally administered.
TBI-223 900 mg SR tablet Prototype 3, orally administered.
TBI-223 1000 mg immediate release (IR) tablet, orally administered
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Worldwide Clinical Trials (WCT)
San Antonio, Texas, 78217, United States
Related Publications (1)
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.
PMID: 40067046DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Majda Benhayoun
- Organization
- TB Alliance
Study Officials
- STUDY CHAIR
Jerry Nedelman
Global Alliance for TB Drug Development
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- This study is partially blinded. The repeat cohort (3b) using a different dosage formulation in Part 1 and subjects in Part 2 will be non-randomized and unblinded.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2018
First Posted
November 29, 2018
Study Start
January 16, 2019
Primary Completion
March 15, 2020
Study Completion
March 15, 2020
Last Updated
December 9, 2024
Results First Posted
December 9, 2024
Record last verified: 2024-10