Phase 1
Completed N=84
A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of TBI-223 in Healthy Adults
Tuberculosis · Tuberculosis, Pulmonary
Source: ClinicalTrials.gov NCT03758612 ↗
Enrolled (actual)
84
Serious AEs
0.0%
Results posted
Dec 2024
Primary outcomePrimary: Number of Participants With Treatment-related Adverse Events — 0; 1; 1; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-related Adverse Events |
0; 1; 1; 0; 0; 0 | — |
| SECONDARY Area Under the Plasma Concentration-time- Curve From the Time of Dosing Extrapolated to Infinity (AUC0-inf) |
1640; 2730; 10700; 8690; 25500; 45000 | — |
| SECONDARY AUC0-t |
1620; 2730; 10700; 8640; 25500; 45900 | — |
| SECONDARY Maximum Plasma Concentration, Determined Directly From Individual Concentration-time- Data (Cmax) |
506; 811; 3090; 1360; 5800; 8530 | — |
| SECONDARY Time of the Maximum Plasma Concentrations (Tmax) |
1.0; 1.50; 1.37; 5.00; 1.75; 1.50 | — |
| SECONDARY The Observed Terminal Elimination Half-life (t1/2) |
2.19; 1.96; 1.94; 3.43; 2.63; 2.93 | — |
| SECONDARY 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 |
42.46; 94.43; 94.73 | — |
| SECONDARY 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 |
103.34; 103.23; 102.79 | — |
| SECONDARY 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. |
151.24; 115.73; 115.70 | — |
| SECONDARY 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 |
53.53; 71.70; 66.31; 81.11; 80.55; 95.71 | — |
| SECONDARY 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 |
35.39; 47.41; 43.85; 70.09; 69.60; 82.70 | — |
Eligibility Criteria
Key Inclusion Criteria
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.
Key Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT03758612). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.