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

NCT04865536 | Completed Phase 1 FDA Drug

• 1 other identifier: TBI-223-CL-002
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Keywords

TB; Tuberculosis; TBI-223; Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (74)

• 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

Study Arms (3)

TBI-223 1800 mg

ACTIVE COMPARATOR

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

TBI-223 2400mg

ACTIVE COMPARATOR

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

TBI-223 Placebo

PLACEBO COMPARATOR

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

Interventions

TBI-223 1800 mg DRUG

3 x 600 mg SR1 tablets

TBI-223 1800 mg

TBI-223 2400mg DRUG

3 x 600 mg SR1 tablets and 1 x 600 mg IR tablets

TBI-223 2400mg

TBI-223 Placebo DRUG

Placebo SR and IR tablets for TBI-223

TBI-223 Placebo

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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

Sponsors & Collaborators

• Global Alliance for TB Drug Development: lead

Study Sites (1)

TKL Research, Inc.

Fair Lawn, New Jersey, 07410, United States

Location

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: 40067046 RESULT

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jerry Nedelman

  Global Alliance for TB Drug Development

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: April 29, 2021
• Study Start: February 3, 2021
• Primary Completion: May 17, 2021
• Study Completion: May 17, 2022
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

US (1)