Study to Evaluate Safety, Tolerability, and the PK Profile of TBI-223 in Healthy Subjects

A Phase 1, Partially-Blinded, Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Include A Single Dose Food-Effect Study to Evaluate the Safety, Tolerability, and the PK Profile of TBI-223 in Healthy Subjects

A Phase 1, Partially-Blinded, Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Include A Single Dose Food-Effect Study to Evaluate the Safety, Tolerability, and the PK Profile of TBI-223 in Healthy Subjects

Study Overview

• Status: Completed
• Conditions: Tuberculosis; Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: TBI-223 1800 mg; Drug: TBI-223 2400mg; Drug: TBI-223 Placebo

Detailed Description

This study was a partially-blinded, placebo-controlled, randomized multiple ascending dose (MAD) study conducted at one study center. Cohorts 1 (1800 mg) and 2 (2400mg) began dosing of TBI-223 or placebo on Day 1 under fasted conditions, followed by a 3-day washout period and then by multiple doses of TBI-223 administered after a high-calorie, high-fat meal (Fed) from Day 4 through Day 17 (total of 14 days). Cohort 1 subjects only received slow-release formulations (SR1) tablets and Cohort 2 subjects received a combination of SR1 tablets with one immediate-release (IR) tablet. Cohort 3 with higher doses was planned in the protocol but as allowed by the protocol, a decision was made to halt the study after the second cohort due to mean Cmax and AUC0-24 after 14 days of dosing at 2400 mg in the second cohort exceeded values that were predicted to be achieved at 3000 mg in the third cohort.

Safety was assessed throughout the study for all subjects. Safety assessments included physical and detailed neurological examinations, vital signs (blood pressure (BP), pulse rate (PR), respiration rate, temperature, and pulse oximetry), 12-lead electrocardiograms (12-lead ECGs), cardiac monitoring, adverse events (AEs), and clinical laboratory tests (including hematology, serology, serum chemistry, coagulation, and urinalysis).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Fair Lawn, New Jersey, United States, 07410
      • TKL Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Key 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 Division of Microbiology and Infectious Diseases 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. 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.
5. 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).

6. 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.
7. Lactose intolerant.
8. History of sensitivity or contraindication to use of linezolid, tedizolid, or any study investigational products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TBI-223 1800 mg; Cohort 1, 3 x 600 mg slow release (SR1) tablets. Administered on Day 1 under fasted conditions, followed by a 3-day washout period and then by multiple doses of TBI-223 administered after a high-calorie, high-fat meal (Fed) from Day 4 through Day 17 (total of 14 days), (n=9)	Drug: TBI-223 1800 mg; 3 x 600 mg SR1 tablets
Active Comparator: TBI-223 2400mg; Cohort 2, 3 x 600 mg SR1 tablets and 1 x 600 mg immediate release (IR) tablets. Administered on Day 1 under fasted conditions, followed by a 3-day washout period and then by multiple doses of TBI-223 administered after a high-calorie, high-fat meal (Fed) from Day 4 through Day 17 (total of 14 days), (n=13)	Drug: TBI-223 2400mg; 3 x 600 mg SR1 tablets and 1 x 600 mg IR tablets
Placebo Comparator: TBI-223 Placebo; Dose matching placebo tablets. Administered on Day 1 under fasted conditions, followed by a 3-day washout period and then by multiple doses of dose matched placebo administered after a high-calorie, high-fat meal (Fed) from Day 4 through Day 17 (total of 14 days), (n=6)	Drug: TBI-223 Placebo; Placebo SR and IR tablets for TBI-223

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment Vital Signs - Blood pressure	Blood pressure measured.	through study completion, 12 weeks.
Safety assessment Vital Signs - Pulse rate	Pulse rate measured.	through study completion, 12 weeks.
Safety assessment Vital Signs - Respiration rate	Respiration rate measured.	through study completion, 12 weeks.
Safety assessment Vital Signs - Temperature	Temperature measured.	through study completion, 12 weeks.
Safety assessment Vital Signs - Pulse oximetry	Pulse oximetry measured.	through study completion, 12 weeks.
Safety assessment - Cardiac monitoring	Safety 12-lead ECGs including ECG QT interval will be recorded and printed for on-site review by the Principal Investigator or designee.	through study completion, 12 weeks.
Safety assessment - Adverse Events (AEs)	AEs recorded.	through study completion, 12 weeks.
Safety assessment Clinical Laboratory Tests - Hematology	Hematology recorded: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell count (RBC), and platelet count.	through study completion, 12 weeks.
Safety assessment Clinical Laboratory Tests - Serology	Serology tests recorded: hepatitis B surface antigen, hepatitis C antibody, and HIV.	through study completion, 12 weeks.
Safety assessment Clinical Laboratory Tests - Serum Chemistry	Serum chemistry recorded: albumin, blood urea nitrogen (BUN), creatinine, total bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), sodium (Na+), potassium (K+), chloride (Cl-), lactate dehydrogenase (LDH), calcium (Ca), uric acid, glucose, gamma-glutamyltransferase (GGT), and magnesium.	through study completion, 12 weeks.
Safety assessment Clinical Laboratory Tests - Coagulation	Coagulation recorded: prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR).	through study completion, 12 weeks.
Safety assessment Clinical Laboratory Tests - Urinalysis	Urinalysis recorded.	through study completion, 12 weeks.
Safety assessment - Serum Pregnancy Testing	Blood collection from female subjects for serum pregnancy testing.	through study completion, 12 weeks.
Safety assessment - Follicle-stimulating hormone (FSH) Levels	Blood collection from postmenopausal women to measure FSH levels.	through study completion, 12 weeks.
Pharmacokinetics, non-food-effect cohorts - AUCtau	AUCtau measured.	Day 1
Pharmacokinetics, non-food-effect cohorts - Cmax	Cmax measured.	Day 1
Pharmacokinetics, non-food-effect cohorts - C24	C24 measured.	Day 1
Pharmacokinetics, non-food-effect cohorts - Cavg	Cavg measured.	Day 1
Pharmacokinetics, non-food-effect cohorts - Tmax	Tmax measured.	Day 1
Pharmacokinetics, non-food-effect cohorts - AUCinf	AUCinf measured if AUCtau ≥ 70% of AUCinf.	Day 1
Pharmacokinetics, non-food-effect cohorts - AUCextrap	AUCextrap measured if AUCtau ≥ 70% of AUCinf.	Day 1
Pharmacokinetics, non-food-effect cohorts - CL/F	CL/F measured if AUCtau ≥ 70% of AUCinf.	Day 1
Pharmacokinetics, non-food-effect cohorts - Vz/F	Vz/F measured if AUCtau ≥ 70% of AUCinf.	Day 1
Pharmacokinetics, non-food-effect cohorts - lambaZ	lambaZ measured if AUCtau ≥ 70% of AUCinf.	Day 1
Pharmacokinetics, non-food-effect cohorts - t1/2	t1/2 measured if AUCtau ≥ 70% of AUCinf.	Day 1
Pharmacokinetics, non-food-effect cohorts - AUCtau	AUCtau measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - Cmax	Cmax measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - Cmin	Cmin measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - Ctrough	Ctrough (i.e., C0) measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - C24	C24 measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - Cavg	Cavg measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - Tmax	Tmax measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - CL/F	CL/F measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - Vz/F	Vz/F measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - lambaZ	lambaZ measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - t1/2	t1/2 measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - RAUC	RAUC measured.	Day 14
Pharmacokinetics, non-food-effect cohorts - RCmax measured.	RCmax measured.	Day 14
Pharmacokinetics, food-effect cohorts - AUCtau	AUCtau measured.	Day 1
Pharmacokinetics, food-effect cohorts - AUCextrap	AUCextrap measured.	Day 1
Pharmacokinetics, food-effect cohorts - AUCinf	AUCinf measured.	Day 1
Pharmacokinetics, food-effect cohorts - Cmax	Cmax measured.	Day 1
Pharmacokinetics, food-effect cohorts - C24	C24 measured	Day 1
Pharmacokinetics, food-effect cohorts - Clast	Clast measured.	Day 1
Pharmacokinetics, food-effect cohorts - Tmax	Tmax measured.	Day 1
Pharmacokinetics, food-effect cohorts - Tlast	Tlast measured.	Day 1
Pharmacokinetics, food-effect cohorts - CL/F	CL/F measured.	Day 1
Pharmacokinetics, food-effect cohorts - Vz/F	Vz/F measured.	Day 1
Pharmacokinetics, food-effect cohorts - lambaZ	lambaZ measured.	Day 1
Pharmacokinetics, food-effect cohorts - t1/2	t1/2 measured.	Day 1
Pharmacokinetics, food-effect cohorts - AUCtau	AUCtau measured. lambaZ, t1/2 should be included if AUCtau ≥ 70% of AUCinf	Day 4
Pharmacokinetics, food-effect cohorts - Cmax	Cmax measured.	Day 4
Pharmacokinetics, food-effect cohorts - C24	C24 measured.	Day 4
Pharmacokinetics, food-effect cohorts - Cavg	Cavg measured.	Day 4
Pharmacokinetics, food-effect cohorts - Tmax	Tmax measured.	Day 4
Pharmacokinetics, food-effect cohorts - AUCinf	AUCinf measured if AUCtau ≥ 70% of AUCinf.	Day 4
Pharmacokinetics, food-effect cohorts - AUCextrap	AUCextrap measured if AUCtau ≥ 70% of AUCinf.	Day 4
Pharmacokinetics, food-effect cohorts - CL/F	CL/F measured if AUCtau ≥ 70% of AUCinf.	Day 4
Pharmacokinetics, food-effect cohorts - Vz/F	Vz/F measured if AUCtau ≥ 70% of AUCinf.	Day 4
Pharmacokinetics, food-effect cohorts - lambaZ	lambaZ measured if AUCtau ≥ 70% of AUCinf.	Day 4
Pharmacokinetics, food-effect cohorts - t1/2	t1/2 measured if AUCtau ≥ 70% of AUCinf.	Day 4
Pharmacokinetics, food-effect cohorts - AUCtau	AUCtau measured.	Day 17
Pharmacokinetics, food-effect cohorts - Cmax	Cmax measured.	Day 17
Pharmacokinetics, food-effect cohorts - Cmin	Cmin measured.	Day 17
Pharmacokinetics, food-effect cohorts - Ctrough	Ctrough (i.e., C0) measured.	Day 17
Pharmacokinetics, food-effect cohorts - C24	C24 measured.	Day 17
Pharmacokinetics, food-effect cohorts - Cavg	Cavg measured.	Day 17
Pharmacokinetics, food-effect cohorts - Tmax	Tmax measured.	Day 17
Pharmacokinetics, food-effect cohorts - CL/F	CL/F measured.	Day 17
Pharmacokinetics, food-effect cohorts - Vz/F	Vz/F measured.	Day 17
Pharmacokinetics, food-effect cohorts - lambaZ	lambaZ measured.	Day 17
Pharmacokinetics, food-effect cohorts - t1/2	t1/2 measured.	Day 17
Pharmacokinetics, food-effect cohorts - RAUC	RAUC measured.	Day 17
Pharmacokinetics, food-effect cohorts - RCmax	RCmax measured.	Day 17

Collaborators and Investigators

• Sponsor: Global Alliance for TB Drug Development
• Investigators: Study Chair: Jerry Nedelman, Global Alliance for TB Drug Development

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Actual): May 17, 2021
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Tuberculosis; TB; Pulmonary Tuberculosis; TBI-223
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: TBI-223-CL-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No