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

Primary Purpose

Tuberculosis, Tuberculosis, Pulmonary

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
1800 mg TBI-223
2400mg TBI-223
3000mg TBI-223
TBI-223 Placebo
TBI-223 Placebo
TBI-223 Placebo
Sponsored by
Global Alliance for TB Drug Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring TB, Tuberculosis, TBI-223, Pulmonary Tuberculosis

Eligibility Criteria

19 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • All volunteers must satisfy the following criteria to be considered for study participation:

    1. Understands study procedures and voluntarily provides written informed consent prior to the start of any study-specific procedures.
    2. Is a healthy adult male or a healthy adult female, 19 to 50 years of age (inclusive) at the time of screening.
    3. Has a body mass index (BMI) ≥18.5 and ≤32.0 (kg/m2) and a body weight of no less than 50.0 kg at the time of screening and check-in.
    4. Is medically healthy with no clinically significant screening results, as determined by the Principal Investigator (e.g., laboratory profiles are normal up to and including Grade 1 per DMID toxicity tables; Appendix 3), medical history, vital signs, ECG, or physical/neurological examination findings. Note: If exclusionary lab criteria are met, values may be confirmed by repeat evaluation.
    5. Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing.
    6. Females of non-childbearing potential, based on having undergone one of the following sterilization procedures at least 6 months before dosing:

      • Hysteroscopic sterilization.
      • Bilateral tubal ligation or bilateral salpingectomy;
      • Hysterectomy; or
      • Bilateral oophorectomy.
      • Or is postmenopausal with amenorrhea for at least 1 year before the first dose with serum FSH levels consistent with postmenopausal status (i.e., greater than 40 mIU/mL) at screening. Or, if female of childbearing potential, must agree to use an allowable form of birth control from screening until 14 days after study completion. The following are allowed birth control methods for this study:
      • Vasectomized partner (at least 6 months before dosing);
      • Non-surgical permanent sterilization (e.g., Essure® procedure) at least 3 months before dosing.
      • Double barrier method (e.g., diaphragm with spermicide; condoms with spermicide).
      • Intrauterine device (IUD).
      • Abstinence (and must agree to use a double barrier method if they become sexually active during the study);
      • Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months before study dosing; and/or
      • Oral, patch, or injected contraceptives, or vaginal hormonal device (i.e. NuvaRing®), in use for at least 3 consecutive months before study dosing.
    7. If a non-vasectomized male (or male vasectomized less than 120 days prior to study start) must agree to the following during study participation and for 90 days after the last administration of study drug:

      • Use a condom with spermicide while engaging in sexual activity or be sexually abstinent
      • Not donate sperm during this time. In the event the sexual partner is surgically sterile or postmenopausal, use of a condom with spermicide is not necessary. None of the birth control restrictions listed above are required for vasectomized males whose procedure was performed more than 120 days before study start.
    8. Is willing to answer inclusion and exclusion criteria questionnaire at check-in.
    9. Is able to comply with the protocol and the assessments therein, including all restrictions.
    10. Is willing and able to remain in the study unit for the entire duration of the assigned confinement period(s), return for outpatient visit(s), and receive a phone call for follow-up questioning about AEs.

Exclusion Criteria:

  • Volunteers will be excluded from study participation for any of the following:

    1. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological (including epilepsy), oncologic, or 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 abnormality on neurologic exam.
    3. History of any illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the subject by their participation in the study.
    4. Surgery within the past 90 days prior to dosing as determined by the Investigator to be clinically relevant, or any history of cholecystectomy.
    5. History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant.
    6. History of sensitivity or contraindication to use of linezolid, tedizolid, or any study investigational products.
    7. Participation in another clinical trial within 30 days prior to dosing.
    8. Female subjects who are pregnant or lactating.
    9. Positive result on a urine drug/alcohol/cotinine screen at Baseline or check-in.
    10. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening. Out-of-range vital signs may be repeated once for confirmation.
    11. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening. Out-of-range vital signs may be repeated once for confirmation.
    12. Any clinically significant ECG abnormality at Screening (as deemed by decision of the Investigator and the Sponsor's Medical Monitor). NOTE: The following may be considered not clinically significant without consulting the Sponsor's Medical Monitor:

      • Mild first-degree A-V block (P-R interval <0.23 sec)
      • Right or left axis deviation
      • Incomplete right bundle branch block
      • Isolated left anterior fascicular block (left anterior hemiblock) in younger athletic subjects
      • Early repolarization
      • Tall T waves
      • RSR in V1/V2 consistent with right ventricular conduction delay (with acceptable QRS)
      • Sinus rhythm or sinus bradycardia with sinus arrhythmia
      • Minimal or moderate voltage criteria for left ventricular hypertrophy (LVH).
    13. 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 ECGs taken at screening and on Day -1, the average QTcF interval of the three ECG recordings will be used to determine qualification.
    14. Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death (such as known coronary artery disease, congestive heart failure, or terminal cancer).
    15. 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 may lower the seizure threshold.
    16. Lactose intolerant. Specific Treatments
    17. Use of any prescription medication within 14 days prior to dosing.
    18. Use of any of the following medications within 30 days before the first dose of study drug or during the study drug treatment period: monoamine oxidase (MAO) inhibitors (phenelzine, tranylcypromine), tricyclic antidepressants (amitriptyline, nortriptyline, protriptyline, doxepin, amoxapine, etc.), antipsychotics such as chlorpromazine and buspirone, serotonin re-uptake inhibitors (fluoxetine, paroxetine, sertraline, etc.), bupropion, agents known to prolong the QTc interval (erythromycin, clarithromycin, astemizole, type Ia [quinidine, procainamide, disopyramide] and III [amiodarone, sotalol] anti-arrhythmics, carbamazepine, sulfonylureas, and meperidine).
    19. Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within 7 days prior to dosing, except acetaminophen. Up to 3 grams per day of acetaminophen is allowed at the discretion of the Investigator prior to dosing.
    20. Use of any drugs or substances known to be significant inhibitors of cytochrome P450 (CYP) enzymes and/or significant inhibitors or substrates of P-glycoprotein (P-gp) and/or organic anion transporting polypeptides (OATP) within 14 days prior to the first dose of study drug.
    21. Use of any drugs or substances known to be inducers of CYP enzymes and/or Pgp, including St. John's Wort, within 30 days prior to the first dose of study drug.
    22. Use of any drugs or substance known to lower the seizure threshold. Specific Laboratory Abnormalities
    23. Serum magnesium, potassium, or calcium laboratory values outside of the normal range at screening. If exclusionary lab criteria are met, values may be confirmed by repeat evaluation.
    24. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
    25. ALT or AST greater than ULN.

Sites / Locations

  • TKL Research, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Placebo Comparator

Active Comparator

Active Comparator

Placebo Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

Cohort 1 TBI-223 1800 mg, fasting

Cohort 1 TBI-23 1800, fed

Cohort 1 Placebo, fed

Cohort 1 Placebo fasting

Cohort 2 TBI-223, 2400mg,fed

Cohort 2 TBI-223, 2400 mg fasting

Cohort 2 Placebo, fed

Cohort 2 Placebo, fasting

Cohort 3 3000mg, fed

Cohort 3 placebo, fed

Arm Description

1800 mg, fasting

TBI-23 1800, fed

Placebo, fed

Placebo fasting

2400mg,fed

2400 mg fasting

Placebo, fed

Placebo, fasting

3000mg, fed

placebo, fed

Outcomes

Primary Outcome Measures

Safety assessment Vital Signs - Blood pressure
Blood pressure measured.
Safety assessment Vital Signs - Pulse rate
Pulse rate measured.
Safety assessment Vital Signs - Respiration rate
Respiration rate measured.
Safety assessment Vital Signs - Temperature
Temperature measured.
Safety assessment Vital Signs - Pulse oximetry
Pulse oximetry measured.
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.
Safety assessment - Adverse Events (AEs)
AEs recorded.
Safety assessment Clinical Laboratory Tests - Hematology
Hematology recorded: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell count (RBC), and platelet count.
Safety assessment Clinical Laboratory Tests - Serology
Serology tests recorded: hepatitis B surface antigen, hepatitis C antibody, and HIV.
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.
Safety assessment Clinical Laboratory Tests - Coagulation
Coagulation recorded: prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR).
Safety assessment Clinical Laboratory Tests - Urinalysis
Urinalysis recorded.
Safety assessment - Serum Pregnancy Testing
Blood collection from female subjects for serum pregnancy testing.
Safety assessment - Follicle-stimulating hormone (FSH) Levels
Blood collection from postmenopausal women to measure FSH levels.
Pharmacokinetics, non-food-effect cohorts - AUCtau
AUCtau measured.
Pharmacokinetics, non-food-effect cohorts - Cmax
Cmax measured.
Pharmacokinetics, non-food-effect cohorts - C24
C24 measured.
Pharmacokinetics, non-food-effect cohorts - Cavg
Cavg measured.
Pharmacokinetics, non-food-effect cohorts - Tmax
Tmax measured.
Pharmacokinetics, non-food-effect cohorts - AUCinf
AUCinf measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, non-food-effect cohorts - AUCextrap
AUCextrap measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, non-food-effect cohorts - CL/F
CL/F measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, non-food-effect cohorts - Vz/F
Vz/F measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, non-food-effect cohorts - lambaZ
lambaZ measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, non-food-effect cohorts - t1/2
t1/2 measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, non-food-effect cohorts - AUCtau
AUCtau measured.
Pharmacokinetics, non-food-effect cohorts - Cmax
Cmax measured.
Pharmacokinetics, non-food-effect cohorts - Cmin
Cmin measured.
Pharmacokinetics, non-food-effect cohorts - Ctrough
Ctrough (i.e., C0) measured.
Pharmacokinetics, non-food-effect cohorts - C24
C24 measured.
Pharmacokinetics, non-food-effect cohorts - Cavg
Cavg measured.
Pharmacokinetics, non-food-effect cohorts - Tmax
Tmax measured.
Pharmacokinetics, non-food-effect cohorts - CL/F
CL/F measured.
Pharmacokinetics, non-food-effect cohorts - Vz/F
Vz/F measured.
Pharmacokinetics, non-food-effect cohorts - lambaZ
lambaZ measured.
Pharmacokinetics, non-food-effect cohorts - t1/2
t1/2 measured.
Pharmacokinetics, non-food-effect cohorts - RAUC
RAUC measured.
Pharmacokinetics, non-food-effect cohorts - RCmax measured.
RCmax measured.
Pharmacokinetics, food-effect cohorts - AUCtau
AUCtau measured.
Pharmacokinetics, food-effect cohorts - AUCextrap
AUCextrap measured.
Pharmacokinetics, food-effect cohorts - AUCinf
AUCinf measured.
Pharmacokinetics, food-effect cohorts - Cmax
Cmax measured.
Pharmacokinetics, food-effect cohorts - C24
C24 measured
Pharmacokinetics, food-effect cohorts - Clast
Clast measured.
Pharmacokinetics, food-effect cohorts - Tmax
Tmax measured.
Pharmacokinetics, food-effect cohorts - Tlast
Tlast measured.
Pharmacokinetics, food-effect cohorts - CL/F
CL/F measured.
Pharmacokinetics, food-effect cohorts - Vz/F
Vz/F measured.
Pharmacokinetics, food-effect cohorts - lambaZ
lambaZ measured.
Pharmacokinetics, food-effect cohorts - t1/2
t1/2 measured.
Pharmacokinetics, food-effect cohorts - AUCtau
AUCtau measured. lambaZ, t1/2 should be included if AUCtau ≥ 70% of AUCinf
Pharmacokinetics, food-effect cohorts - Cmax
Cmax measured.
Pharmacokinetics, food-effect cohorts - C24
C24 measured.
Pharmacokinetics, food-effect cohorts - Cavg
Cavg measured.
Pharmacokinetics, food-effect cohorts - Tmax
Tmax measured.
Pharmacokinetics, food-effect cohorts - AUCinf
AUCinf measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, food-effect cohorts - AUCextrap
AUCextrap measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, food-effect cohorts - CL/F
CL/F measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, food-effect cohorts - Vz/F
Vz/F measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, food-effect cohorts - lambaZ
lambaZ measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, food-effect cohorts - t1/2
t1/2 measured if AUCtau ≥ 70% of AUCinf.
Pharmacokinetics, food-effect cohorts - AUCtau
AUCtau measured.
Pharmacokinetics, food-effect cohorts - Cmax
Cmax measured.
Pharmacokinetics, food-effect cohorts - Cmin
Cmin measured.
Pharmacokinetics, food-effect cohorts - Ctrough
Ctrough (i.e., C0) measured.
Pharmacokinetics, food-effect cohorts - C24
C24 measured.
Pharmacokinetics, food-effect cohorts - Cavg
Cavg measured.
Pharmacokinetics, food-effect cohorts - Tmax
Tmax measured.
Pharmacokinetics, food-effect cohorts - CL/F
CL/F measured.
Pharmacokinetics, food-effect cohorts - Vz/F
Vz/F measured.
Pharmacokinetics, food-effect cohorts - lambaZ
lambaZ measured.
Pharmacokinetics, food-effect cohorts - t1/2
t1/2 measured.
Pharmacokinetics, food-effect cohorts - RAUC
RAUC measured.
Pharmacokinetics, food-effect cohorts - RCmax
RCmax measured.

Secondary Outcome Measures

Full Information

First Posted
February 22, 2021
Last Updated
April 13, 2022
Sponsor
Global Alliance for TB Drug Development
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1. Study Identification

Unique Protocol Identification Number
NCT04865536
Brief Title
Study to Evaluate Safety, Tolerability, and the PK Profile of TBI-223 in Healthy Subjects
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
February 16, 2021 (Actual)
Primary Completion Date
May 15, 2021 (Actual)
Study Completion Date
March 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Global Alliance for TB Drug Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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
Detailed Description
This is a partially-blinded, placebo-controlled, randomized multiple ascending dose (MAD) study to be conducted at one study center. Thirty-six (36) subjects will be enrolled in 3 cohorts with 12 subjects per cohort. Within each cohort, 9 subjects will be assigned to receive active treatment and 3 subjects will receive placebo. Each subject will participate in one dose level. The first 2 cohorts (food-effect cohorts) will begin dosing of TBI-223 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 from Day 4 through Day 17 (total of 14 days). The third cohort (nonfood- effect cohort) will begin dosing of TBI-223 on Day 1 and continue through Day 14, all doses administered after a high-calorie, high-fat meal. Each subject will be administered TBI-223 tablets (SR1 or IR or a combination of both formulations) or placebo once daily for 14 days with corresponding pharmacokinetic measurements. After each dose cohort, the Sponsor and Investigator will review the pharmacokinetic and safety data before proceeding to the next dose level. Dose escalation to the next cohort (i.e., dose level) or decisions regarding changed or additional cohorts will not take place until the Sponsor, in conjunction with the Principal Investigator and dose escalating committee, has determined that adequate safety, tolerability, and pharmacokinetics from the previous cohort(s) have been demonstrated to permit proceeding to the next cohort. Additional cohorts (up to 12 subjects per cohort) may be enrolled if deemed appropriate by the Sponsor to study other dose levels, change proposed cohorts, or to study a different dosage formulation The Institutional Review Board (IRB) should be immediately notified of the dose escalation or any revised approach for review and approval. Safety will be assessed throughout the study for all subjects. Safety assessments will include physical and detailed neurological examinations, vital signs (blood pressure, pulse rate, respiration rate, temperature and pulse oximetry), electrocardiograms (ECGs), cardiac monitoring, adverse events (AEs), and clinical laboratory tests (including hematology, serology, serum chemistry, coagulation, and urinalysis). Blood and urine will be collected for clinical laboratory evaluations. The Principal Investigator, in conjunction with the Sponsor may collect additional blood if necessary, for repeat laboratory or safety evaluations including AE follow up. Female subjects will have blood collected for serum pregnancy testing. Females claiming postmenopausal status will have blood collected to measure follicle stimulating hormone (FSH) levels. During each cohort, blood samples (trough samples) will be obtained before each dose of study drug, and at the time points on the events schedule. Plasma pharmacokinetic samples will be analyzed for TBI-223 and M2 using validated analytical methods. Appropriate pharmacokinetic parameters will be calculated using non compartmental methods.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Tuberculosis, Pulmonary
Keywords
TB, Tuberculosis, TBI-223, Pulmonary Tuberculosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 TBI-223 1800 mg, fasting
Arm Type
Active Comparator
Arm Description
1800 mg, fasting
Arm Title
Cohort 1 TBI-23 1800, fed
Arm Type
Active Comparator
Arm Description
TBI-23 1800, fed
Arm Title
Cohort 1 Placebo, fed
Arm Type
Placebo Comparator
Arm Description
Placebo, fed
Arm Title
Cohort 1 Placebo fasting
Arm Type
Placebo Comparator
Arm Description
Placebo fasting
Arm Title
Cohort 2 TBI-223, 2400mg,fed
Arm Type
Active Comparator
Arm Description
2400mg,fed
Arm Title
Cohort 2 TBI-223, 2400 mg fasting
Arm Type
Active Comparator
Arm Description
2400 mg fasting
Arm Title
Cohort 2 Placebo, fed
Arm Type
Placebo Comparator
Arm Description
Placebo, fed
Arm Title
Cohort 2 Placebo, fasting
Arm Type
Placebo Comparator
Arm Description
Placebo, fasting
Arm Title
Cohort 3 3000mg, fed
Arm Type
Active Comparator
Arm Description
3000mg, fed
Arm Title
Cohort 3 placebo, fed
Arm Type
Placebo Comparator
Arm Description
placebo, fed
Intervention Type
Drug
Intervention Name(s)
1800 mg TBI-223
Intervention Description
3 x 600 mg SR1 tablets
Intervention Type
Drug
Intervention Name(s)
2400mg TBI-223
Intervention Description
3 x 600 mg SR1 tablets and 1 x 600 mg IR tablets
Intervention Type
Drug
Intervention Name(s)
3000mg TBI-223
Intervention Description
4 x 600 mg SR1 tablets and 1 x 600 mg IR tablets
Intervention Type
Drug
Intervention Name(s)
TBI-223 Placebo
Intervention Description
3 x Placebo tablets
Intervention Type
Drug
Intervention Name(s)
TBI-223 Placebo
Intervention Description
4 x Placebo tablets
Intervention Type
Drug
Intervention Name(s)
TBI-223 Placebo
Intervention Description
5 x Placebo tablets
Primary Outcome Measure Information:
Title
Safety assessment Vital Signs - Blood pressure
Description
Blood pressure measured.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Vital Signs - Pulse rate
Description
Pulse rate measured.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Vital Signs - Respiration rate
Description
Respiration rate measured.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Vital Signs - Temperature
Description
Temperature measured.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Vital Signs - Pulse oximetry
Description
Pulse oximetry measured.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment - Cardiac monitoring
Description
Safety 12-lead ECGs including ECG QT interval will be recorded and printed for on-site review by the Principal Investigator or designee.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment - Adverse Events (AEs)
Description
AEs recorded.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Clinical Laboratory Tests - Hematology
Description
Hematology recorded: hemoglobin, hematocrit, total and differential leukocyte count, red blood cell count (RBC), and platelet count.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Clinical Laboratory Tests - Serology
Description
Serology tests recorded: hepatitis B surface antigen, hepatitis C antibody, and HIV.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Clinical Laboratory Tests - Serum Chemistry
Description
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.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Clinical Laboratory Tests - Coagulation
Description
Coagulation recorded: prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR).
Time Frame
through study completion, 12 weeks.
Title
Safety assessment Clinical Laboratory Tests - Urinalysis
Description
Urinalysis recorded.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment - Serum Pregnancy Testing
Description
Blood collection from female subjects for serum pregnancy testing.
Time Frame
through study completion, 12 weeks.
Title
Safety assessment - Follicle-stimulating hormone (FSH) Levels
Description
Blood collection from postmenopausal women to measure FSH levels.
Time Frame
through study completion, 12 weeks.
Title
Pharmacokinetics, non-food-effect cohorts - AUCtau
Description
AUCtau measured.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - Cmax
Description
Cmax measured.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - C24
Description
C24 measured.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - Cavg
Description
Cavg measured.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - Tmax
Description
Tmax measured.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - AUCinf
Description
AUCinf measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - AUCextrap
Description
AUCextrap measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - CL/F
Description
CL/F measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - Vz/F
Description
Vz/F measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - lambaZ
Description
lambaZ measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - t1/2
Description
t1/2 measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 1
Title
Pharmacokinetics, non-food-effect cohorts - AUCtau
Description
AUCtau measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - Cmax
Description
Cmax measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - Cmin
Description
Cmin measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - Ctrough
Description
Ctrough (i.e., C0) measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - C24
Description
C24 measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - Cavg
Description
Cavg measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - Tmax
Description
Tmax measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - CL/F
Description
CL/F measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - Vz/F
Description
Vz/F measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - lambaZ
Description
lambaZ measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - t1/2
Description
t1/2 measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - RAUC
Description
RAUC measured.
Time Frame
Day 14
Title
Pharmacokinetics, non-food-effect cohorts - RCmax measured.
Description
RCmax measured.
Time Frame
Day 14
Title
Pharmacokinetics, food-effect cohorts - AUCtau
Description
AUCtau measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - AUCextrap
Description
AUCextrap measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - AUCinf
Description
AUCinf measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - Cmax
Description
Cmax measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - C24
Description
C24 measured
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - Clast
Description
Clast measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - Tmax
Description
Tmax measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - Tlast
Description
Tlast measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - CL/F
Description
CL/F measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - Vz/F
Description
Vz/F measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - lambaZ
Description
lambaZ measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - t1/2
Description
t1/2 measured.
Time Frame
Day 1
Title
Pharmacokinetics, food-effect cohorts - AUCtau
Description
AUCtau measured. lambaZ, t1/2 should be included if AUCtau ≥ 70% of AUCinf
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - Cmax
Description
Cmax measured.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - C24
Description
C24 measured.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - Cavg
Description
Cavg measured.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - Tmax
Description
Tmax measured.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - AUCinf
Description
AUCinf measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - AUCextrap
Description
AUCextrap measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - CL/F
Description
CL/F measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - Vz/F
Description
Vz/F measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - lambaZ
Description
lambaZ measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - t1/2
Description
t1/2 measured if AUCtau ≥ 70% of AUCinf.
Time Frame
Day 4
Title
Pharmacokinetics, food-effect cohorts - AUCtau
Description
AUCtau measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - Cmax
Description
Cmax measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - Cmin
Description
Cmin measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - Ctrough
Description
Ctrough (i.e., C0) measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - C24
Description
C24 measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - Cavg
Description
Cavg measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - Tmax
Description
Tmax measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - CL/F
Description
CL/F measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - Vz/F
Description
Vz/F measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - lambaZ
Description
lambaZ measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - t1/2
Description
t1/2 measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - RAUC
Description
RAUC measured.
Time Frame
Day 17
Title
Pharmacokinetics, food-effect cohorts - RCmax
Description
RCmax measured.
Time Frame
Day 17

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: All volunteers must satisfy the following criteria to be considered for study participation: Understands study procedures and voluntarily provides written informed consent prior to the start of any study-specific procedures. Is a healthy adult male or a healthy adult 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 at the time of screening and check-in. Is medically healthy with no clinically significant screening results, as determined by the Principal Investigator (e.g., laboratory profiles are normal up to and including Grade 1 per DMID toxicity tables; Appendix 3), medical history, vital signs, ECG, or physical/neurological examination findings. Note: If exclusionary lab criteria are met, values may be confirmed by repeat evaluation. Has not used tobacco- or nicotine-containing products (including smoking cessation products), for a minimum of 6 months before dosing. Females of non-childbearing potential, based on having undergone one of the following sterilization procedures at least 6 months before dosing: Hysteroscopic sterilization. Bilateral tubal ligation or bilateral salpingectomy; Hysterectomy; or Bilateral oophorectomy. Or is postmenopausal with amenorrhea for at least 1 year before the first dose with serum FSH levels consistent with postmenopausal status (i.e., greater than 40 mIU/mL) at screening. Or, if female of childbearing potential, must agree to use an allowable form of birth control from screening until 14 days after study completion. The following are allowed birth control methods for this study: Vasectomized partner (at least 6 months before dosing); Non-surgical permanent sterilization (e.g., Essure® procedure) at least 3 months before dosing. Double barrier method (e.g., diaphragm with spermicide; condoms with spermicide). Intrauterine device (IUD). Abstinence (and must agree to use a double barrier method if they become sexually active during the study); Implanted or intrauterine hormonal contraceptives in use for at least 6 consecutive months before study dosing; and/or Oral, patch, or injected contraceptives, or vaginal hormonal device (i.e. NuvaRing®), in use for at least 3 consecutive months before study dosing. If a non-vasectomized male (or male vasectomized less than 120 days prior to study start) must agree to the following during study participation and for 90 days after the last administration of study drug: Use a condom with spermicide while engaging in sexual activity or be sexually abstinent Not donate sperm during this time. In the event the sexual partner is surgically sterile or postmenopausal, use of a condom with spermicide is not necessary. None of the birth control restrictions listed above are required for vasectomized males whose procedure was performed more than 120 days before study start. Is willing to answer inclusion and exclusion criteria questionnaire at check-in. Is able to comply with the protocol and the assessments therein, including all restrictions. Is willing and able to remain in the study unit for the entire duration of the assigned confinement period(s), return for outpatient visit(s), and receive a phone call for follow-up questioning about AEs. Exclusion Criteria: Volunteers will be excluded from study participation for any of the following: History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological (including epilepsy), oncologic, or 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 abnormality on neurologic exam. History of any illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk to the subject by their participation in the study. Surgery within the past 90 days prior to dosing as determined by the Investigator to be clinically relevant, or any history of cholecystectomy. History or presence of alcoholism or drug abuse within the past 2 years as determined by the Investigator to be clinically relevant. History of sensitivity or contraindication to use of linezolid, tedizolid, or any study investigational products. Participation in another clinical trial within 30 days prior to dosing. Female subjects who are pregnant or lactating. Positive result on a urine drug/alcohol/cotinine screen at Baseline or check-in. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening. Out-of-range vital signs may be repeated once for confirmation. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening. Out-of-range vital signs may be repeated once for confirmation. Any clinically significant ECG abnormality at Screening (as deemed by decision of the Investigator and the Sponsor's Medical Monitor). NOTE: The following may be considered not clinically significant without consulting the Sponsor's Medical Monitor: Mild first-degree A-V block (P-R interval <0.23 sec) Right or left axis deviation Incomplete right bundle branch block Isolated left anterior fascicular block (left anterior hemiblock) in younger athletic subjects Early repolarization Tall T waves RSR in V1/V2 consistent with right ventricular conduction delay (with acceptable QRS) Sinus rhythm or sinus bradycardia with sinus arrhythmia Minimal or moderate voltage criteria for left ventricular hypertrophy (LVH). 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 ECGs taken at screening and on Day -1, the average QTcF interval of the three ECG recordings will be used to determine qualification. Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that could be 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 may lower the seizure threshold. Lactose intolerant. Specific Treatments Use of any prescription medication within 14 days prior to dosing. Use of any of the following medications within 30 days before the first dose of study drug or during the study drug treatment period: monoamine oxidase (MAO) inhibitors (phenelzine, tranylcypromine), tricyclic antidepressants (amitriptyline, nortriptyline, protriptyline, doxepin, amoxapine, etc.), antipsychotics such as chlorpromazine and buspirone, serotonin re-uptake inhibitors (fluoxetine, paroxetine, sertraline, etc.), bupropion, agents known to prolong the QTc interval (erythromycin, clarithromycin, astemizole, type Ia [quinidine, procainamide, disopyramide] and III [amiodarone, sotalol] anti-arrhythmics, carbamazepine, sulfonylureas, and meperidine). Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within 7 days prior to dosing, except acetaminophen. Up to 3 grams per day of acetaminophen is allowed at the discretion of the Investigator prior to dosing. Use of any drugs or substances known to be significant inhibitors of cytochrome P450 (CYP) enzymes and/or significant inhibitors or substrates of P-glycoprotein (P-gp) and/or organic anion transporting polypeptides (OATP) within 14 days prior to the first dose of study drug. Use of any drugs or substances known to be inducers of CYP enzymes and/or Pgp, including St. John's Wort, within 30 days prior to the first dose of study drug. Use of any drugs or substance known to lower the seizure threshold. Specific Laboratory Abnormalities Serum magnesium, potassium, or calcium laboratory values outside of the normal range at screening. If exclusionary lab criteria are met, values may be confirmed by repeat evaluation. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). ALT or AST greater than ULN.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Bruinenberg, MD, MBA
Organizational Affiliation
Global Alliance for TB Drug Development
Official's Role
Study Chair
Facility Information:
Facility Name
TKL Research, Inc.
City
Fair Lawn
State/Province
New Jersey
ZIP/Postal Code
07410
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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