Tuberculosis
Conditions
Keywords
Tuberculosis, TBA-354, Pulmonary Tuberculosis, TB
Brief summary
The objective of the study is to evaluate the safety and tolerability of multiple doses of TBA-354 in healthy subjects.
Detailed description
This is a randomized, double-blind, placebo-controlled, multiple ascending dose study conducted at one study center in the United States. Three (3) multiple ascending dose cohorts are planned with twelve (12) healthy subjects (9 active and 3 placebo) in each cohort. There will also be a dose formulation comparison cohort, enrollment of six (6) subjects is planned. An additional multiple dose cohort of twelve (12) subjects may be enrolled. Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and pharmacokinetics (PK) assessment of TBA-354. Dose escalation to the next cohort (i.e., dose level) will not take place until the Sponsor, in conjunction with the Principal Investigator, has determined that adequate safety, tolerability and PK from the previous cohort has been demonstrated to permit proceeding to the next cohort. Upon review of cohort data, the Sponsor, in conjunction with the Principal Investigator, may decide to: 1. Escalate the dose as planned. 2. Evaluate an intermediate dose level prior to proceeding to the next planned dose level if concerns arise from PK and safety that do not warrant in ceasing escalation. 3. Repeat a given dose level in a new cohort of subjects. 4. Increase the dose of the next cohort if the PK is lower than expected in the previous cohort. 5. Add a cohort if the PK is lower than expected after a cohort and there are no safety concerns. 6. Halt the study. During dose escalation, at no time will the projected Cmax of any individual exceed 7.6 µg/mL, which is the highest mean value at the no-observed-adverse-effect-level from the 3-month log toxicology study TBA 354 NCLN-103. The predicted median Cmax of the final cohort can exceed 3.2 µg/mL only if there have been no safety concerns. Subjects in the Multiple Ascending Dose (MAD) Cohorts will be housed in the Celerion clinic from check-in to Day 15. Subjects will return to the clinic each day from Day 16-Day 21 and have a final one-week follow up phone interview upon completion. Subjects in the Dose Formulation Cohort will be housed in the Clerion clinic from check-in to Day 3, visit the clinic each day for Days 4-7, and be housed in the clinic for Days 14-16. Then subjects will return for a daily visit for Days 17-20, and be contacted for a final one-week follow up phone interview upon completion on Day 28.
Interventions
DRUGTBA-354
DRUGTBA-354 Placebo
Sponsors
Global Alliance for TB Drug Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adult male and females of non-childbearing potential, 19 to 50 years of age (inclusive) at the time of screening. 2. Body mass index (BMI) ≥ 18.5 and ≤ 32.0 (kg/m2) and a body weight of no less than 50.0 kg. 3. Medically healthy with no clinically significant screening results (e.g., laboratory profiles, medical histories, vital signs, ECGs, physical examination) as deemed by the Investigator. 4. No use of tobacco or nicotine containing products (including smoking cessation products), for a minimum of 6 months prior to dosing. 5. Females of non-childbearing potential, having undergone one of the following sterilization procedures at least 6 months prior to dosing: * Hysteroscopic sterilization * Bilateral tubal ligation or bilateral salpingectomy * Hysterectomy * Bilateral oophorectomy * or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with serum follicle stimulating hormone (FSH) levels consistent with postmenopausal status at screening. 6. Non-vasectomized males (or males vasectomized less than 120 days prior to study start), must agree to the following during study participation and for 90 days following 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, use of a condom with spermicide is not necessary. None of the restrictions listed above are required for vasectomized males whose procedure was performed more than 120 days prior to study start. 7. Willing to answer inclusion and
Exclusion criteria
questionnaire at check-in. 8. Subject understands study procedures and provides written informed consent for the trial. 9. Be able to comply with the protocol and the assessments therein, including all restrictions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The comparison of the percentage of subjects per dose cohort with treatment emergent adverse events (TEAEs) from Days 1 to 28 compared to placebo | Multiple Ascending Dose Cohorts: Days 1-28, Dose Formulation Cohort: Days 1-28 | — |
| The percent of subjects per cohort with safety electrocardiogram change-from-baseline QTcF intervals of >30 milliseconds and =>60 milliseconds. | Multiple Ascending Dose Data Time Point Days 1-3, 8, 12, 14-15, 21; Dose Formulation Cohort Data Time Point Days 1-3,7,14-16, 20 | QTcF = QT interval correct by Fridericia's method, percent = number of events/number of subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The mean Tmax of TBA-354 per dose cohort in plasma following dosing | Multiple Ascending Dose Cohort: Days 1-14, Dose Formulation Cohort: Days 1-20 | Acronyms: Tmax = Time of the maximum drug concentration (obtained without interpolation). |
| The mean Cmax of TBA-354 per dose cohort in plasma following dosing | Multiple Ascending Dose Cohort: Days 1-14, Dose Formulation Cohort: Days 1-20 | Acronyms: Cmax= Maximum observed drug concentration |
| The mean AUC0-24 of TBA-354 per dose cohort in plasma following dosing | Multiple Ascending Dose Cohort: Days 1-14, Dose Formulation Cohort: Days 1-20 | Acronyms: AUC0-24= Area under concentration time curve 0 to 24 hours |
Outcome results
None listed