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Completed

NCT Number: NCT04865536

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

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Key information

Conditions

Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Lung Diseases Mycobacterium Infections Respiratory Tract Diseases Respiratory Tract Infections Tuberculosis, Pulmonary

Age range

19 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

TKL Research, Inc.

Fair Lawn, New Jersey, 07410, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TBI-223 1800 mg

Drug

3 x 600 mg SR1 tablets

TBI-223 2400mg

Drug

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

TBI-223 Placebo

Drug

Placebo SR and IR tablets for TBI-223

Primary outcomes

  1. Safety assessment Vital Signs - Blood pressure

    Time frame: through study completion, 12 weeks.

    Blood pressure measured.

  2. Safety assessment Vital Signs - Pulse rate

    Time frame: through study completion, 12 weeks.

    Pulse rate measured.

  3. Safety assessment Vital Signs - Respiration rate

    Time frame: through study completion, 12 weeks.

    Respiration rate measured.

  4. Safety assessment Vital Signs - Temperature

    Time frame: through study completion, 12 weeks.

    Temperature measured.

  5. Safety assessment Vital Signs - Pulse oximetry

    Time frame: through study completion, 12 weeks.

    Pulse oximetry measured.

  6. Safety assessment - Cardiac monitoring

    Time frame: through study completion, 12 weeks.

    Safety 12-lead ECGs including ECG QT interval will be recorded and printed for on-site review by the Principal Investigator or designee.

  7. Safety assessment - Adverse Events (AEs)

    Time frame: through study completion, 12 weeks.

    AEs recorded.

  8. Safety assessment Clinical Laboratory Tests - Hematology

    Time frame: through study completion, 12 weeks.

    Hematology recorded: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell count (RBC), and platelet count.

  9. Safety assessment Clinical Laboratory Tests - Serology

    Time frame: through study completion, 12 weeks.

    Serology tests recorded: hepatitis B surface antigen, hepatitis C antibody, and HIV.

  10. Safety assessment Clinical Laboratory Tests - Serum Chemistry

    Time frame: through study completion, 12 weeks.

    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.

  11. Safety assessment Clinical Laboratory Tests - Coagulation

    Time frame: through study completion, 12 weeks.

    Coagulation recorded: prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR).

  12. Safety assessment Clinical Laboratory Tests - Urinalysis

    Time frame: through study completion, 12 weeks.

    Urinalysis recorded.

  13. Safety assessment - Serum Pregnancy Testing

    Time frame: through study completion, 12 weeks.

    Blood collection from female subjects for serum pregnancy testing.

  14. Safety assessment - Follicle-stimulating hormone (FSH) Levels

    Time frame: through study completion, 12 weeks.

    Blood collection from postmenopausal women to measure FSH levels.

  15. Pharmacokinetics, non-food-effect cohorts - AUCtau

    Time frame: Day 1

    AUCtau measured.

  16. Pharmacokinetics, non-food-effect cohorts - Cmax

    Time frame: Day 1

    Cmax measured.

  17. Pharmacokinetics, non-food-effect cohorts - C24

    Time frame: Day 1

    C24 measured.

  18. Pharmacokinetics, non-food-effect cohorts - Cavg

    Time frame: Day 1

    Cavg measured.

  19. Pharmacokinetics, non-food-effect cohorts - Tmax

    Time frame: Day 1

    Tmax measured.

  20. Pharmacokinetics, non-food-effect cohorts - AUCinf

    Time frame: Day 1

    AUCinf measured if AUCtau ≥ 70% of AUCinf.

  21. Pharmacokinetics, non-food-effect cohorts - AUCextrap

    Time frame: Day 1

    AUCextrap measured if AUCtau ≥ 70% of AUCinf.

  22. Pharmacokinetics, non-food-effect cohorts - CL/F

    Time frame: Day 1

    CL/F measured if AUCtau ≥ 70% of AUCinf.

  23. Pharmacokinetics, non-food-effect cohorts - Vz/F

    Time frame: Day 1

    Vz/F measured if AUCtau ≥ 70% of AUCinf.

  24. Pharmacokinetics, non-food-effect cohorts - lambaZ

    Time frame: Day 1

    lambaZ measured if AUCtau ≥ 70% of AUCinf.

  25. Pharmacokinetics, non-food-effect cohorts - t1/2

    Time frame: Day 1

    t1/2 measured if AUCtau ≥ 70% of AUCinf.

  26. Pharmacokinetics, non-food-effect cohorts - AUCtau

    Time frame: Day 14

    AUCtau measured.

  27. Pharmacokinetics, non-food-effect cohorts - Cmax

    Time frame: Day 14

    Cmax measured.

  28. Pharmacokinetics, non-food-effect cohorts - Cmin

    Time frame: Day 14

    Cmin measured.

  29. Pharmacokinetics, non-food-effect cohorts - Ctrough

    Time frame: Day 14

    Ctrough (i.e., C0) measured.

  30. Pharmacokinetics, non-food-effect cohorts - C24

    Time frame: Day 14

    C24 measured.

  31. Pharmacokinetics, non-food-effect cohorts - Cavg

    Time frame: Day 14

    Cavg measured.

  32. Pharmacokinetics, non-food-effect cohorts - Tmax

    Time frame: Day 14

    Tmax measured.

  33. Pharmacokinetics, non-food-effect cohorts - CL/F

    Time frame: Day 14

    CL/F measured.

  34. Pharmacokinetics, non-food-effect cohorts - Vz/F

    Time frame: Day 14

    Vz/F measured.

  35. Pharmacokinetics, non-food-effect cohorts - lambaZ

    Time frame: Day 14

    lambaZ measured.

  36. Pharmacokinetics, non-food-effect cohorts - t1/2

    Time frame: Day 14

    t1/2 measured.

  37. Pharmacokinetics, non-food-effect cohorts - RAUC

    Time frame: Day 14

    RAUC measured.

  38. Pharmacokinetics, non-food-effect cohorts - RCmax measured.

    Time frame: Day 14

    RCmax measured.

  39. Pharmacokinetics, food-effect cohorts - AUCtau

    Time frame: Day 1

    AUCtau measured.

  40. Pharmacokinetics, food-effect cohorts - AUCextrap

    Time frame: Day 1

    AUCextrap measured.

  41. Pharmacokinetics, food-effect cohorts - AUCinf

    Time frame: Day 1

    AUCinf measured.

  42. Pharmacokinetics, food-effect cohorts - Cmax

    Time frame: Day 1

    Cmax measured.

  43. Pharmacokinetics, food-effect cohorts - C24

    Time frame: Day 1

    C24 measured

  44. Pharmacokinetics, food-effect cohorts - Clast

    Time frame: Day 1

    Clast measured.

  45. Pharmacokinetics, food-effect cohorts - Tmax

    Time frame: Day 1

    Tmax measured.

  46. Pharmacokinetics, food-effect cohorts - Tlast

    Time frame: Day 1

    Tlast measured.

  47. Pharmacokinetics, food-effect cohorts - CL/F

    Time frame: Day 1

    CL/F measured.

  48. Pharmacokinetics, food-effect cohorts - Vz/F

    Time frame: Day 1

    Vz/F measured.

  49. Pharmacokinetics, food-effect cohorts - lambaZ

    Time frame: Day 1

    lambaZ measured.

  50. Pharmacokinetics, food-effect cohorts - t1/2

    Time frame: Day 1

    t1/2 measured.

  51. Pharmacokinetics, food-effect cohorts - AUCtau

    Time frame: Day 4

    AUCtau measured. lambaZ, t1/2 should be included if AUCtau ≥ 70% of AUCinf

  52. Pharmacokinetics, food-effect cohorts - Cmax

    Time frame: Day 4

    Cmax measured.

  53. Pharmacokinetics, food-effect cohorts - C24

    Time frame: Day 4

    C24 measured.

  54. Pharmacokinetics, food-effect cohorts - Cavg

    Time frame: Day 4

    Cavg measured.

  55. Pharmacokinetics, food-effect cohorts - Tmax

    Time frame: Day 4

    Tmax measured.

  56. Pharmacokinetics, food-effect cohorts - AUCinf

    Time frame: Day 4

    AUCinf measured if AUCtau ≥ 70% of AUCinf.

  57. Pharmacokinetics, food-effect cohorts - AUCextrap

    Time frame: Day 4

    AUCextrap measured if AUCtau ≥ 70% of AUCinf.

  58. Pharmacokinetics, food-effect cohorts - CL/F

    Time frame: Day 4

    CL/F measured if AUCtau ≥ 70% of AUCinf.

  59. Pharmacokinetics, food-effect cohorts - Vz/F

    Time frame: Day 4

    Vz/F measured if AUCtau ≥ 70% of AUCinf.

  60. Pharmacokinetics, food-effect cohorts - lambaZ

    Time frame: Day 4

    lambaZ measured if AUCtau ≥ 70% of AUCinf.

  61. Pharmacokinetics, food-effect cohorts - t1/2

    Time frame: Day 4

    t1/2 measured if AUCtau ≥ 70% of AUCinf.

  62. Pharmacokinetics, food-effect cohorts - AUCtau

    Time frame: Day 17

    AUCtau measured.

  63. Pharmacokinetics, food-effect cohorts - Cmax

    Time frame: Day 17

    Cmax measured.

  64. Pharmacokinetics, food-effect cohorts - Cmin

    Time frame: Day 17

    Cmin measured.

  65. Pharmacokinetics, food-effect cohorts - Ctrough

    Time frame: Day 17

    Ctrough (i.e., C0) measured.

  66. Pharmacokinetics, food-effect cohorts - C24

    Time frame: Day 17

    C24 measured.

  67. Pharmacokinetics, food-effect cohorts - Cavg

    Time frame: Day 17

    Cavg measured.

  68. Pharmacokinetics, food-effect cohorts - Tmax

    Time frame: Day 17

    Tmax measured.

  69. Pharmacokinetics, food-effect cohorts - CL/F

    Time frame: Day 17

    CL/F measured.

  70. Pharmacokinetics, food-effect cohorts - Vz/F

    Time frame: Day 17

    Vz/F measured.

  71. Pharmacokinetics, food-effect cohorts - lambaZ

    Time frame: Day 17

    lambaZ measured.

  72. Pharmacokinetics, food-effect cohorts - t1/2

    Time frame: Day 17

    t1/2 measured.

  73. Pharmacokinetics, food-effect cohorts - RAUC

    Time frame: Day 17

    RAUC measured.

  74. Pharmacokinetics, food-effect cohorts - RCmax

    Time frame: Day 17

    RCmax measured.

Sponsors and collaborators

Lead sponsor

Global Alliance for TB Drug Development

Other

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2021
Study completion
2022
First posted
Apr 29, 2021
Registry last updated
Jun 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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