Tuberculosis
Conditions
Keywords
Tuberculosis, TBA-354, Pulmonary Tuberculosis, TB
Brief summary
The objective of this study is to evaluate the safety and tolerability of single oral doses of TBA-354 when administered to healthy adult subjects.
Detailed description
This is a randomized, double-blind, placebo-controlled, single ascending dose study conducted at one study center in the United States. Six (6) cohorts of 8 subjects each (6 active and 2 placebo), with one cohort crossing over to assess food effect, are planned for evaluation. Subjects will participate in only one cohort. Safety will be assessed throughout the study; serial ECGs and serial blood samples will be collected for the safety and 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 dose as planned. 2. Evaluate an intermediate dose level prior to proceeding to the next planned dose level if concerns arise from signs and symptoms that do not warrant ceasing escalation as described above. 3. Repeat a given dose level in a new cohort of subjects. 4. Halt the study. Blinded interim PK analyses will be performed for the dose escalation decisions, to select the intermediate dose for the food effect cohort, and to reconsider the sampling time points as the study progresses. Subjects will be housed in the Celerion clinic from at least 24 hours prior (from Day -2), until 48 hours after dosing. Subjects will return for subsequent follow up safety and PK assessments on Days 4 to 7 and will be contacted via a phone call for follow-up questioning about adverse events 7 days later (Study Day 14). One cohort will return after a washout of at least 14 days or five half-lives (whichever is longer) of their fasting dose to receive the same intermediate dose (TBD mg) under fed conditions.
Interventions
DRUGTBA-354
TBA-354 supplied as a 20 mg /mL suspension and matching placebo suspension for oral administration.
OTHERPlacebo
Placebo Suspension
Sponsors
Global Alliance for TB Drug Development
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects must fulfill all of the following inclusion criteria and none of the
Exclusion criteria
to be eligible for participation in the study, unless otherwise specified. Subjects must continue to meet all inclusion criteria to be able to participate in the Food Effect study. 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 kg. 3. Medically healthy with no clinically significant screening results (e.g., laboratory profiles, medical histories, vital signs, electrocardiograms (ECGs), physical examination) as deemed by the Principal 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 have undergone one of the following sterilization procedures at least 6 months prior to dosing: i. Hysteroscopic sterilization ii. Bilateral tubal ligation or bilateral salpingectomy iii. Hysterectomy iv. Bilateral oophorectomy v. or be postmenopausal with amenorrhea for at least 1 year prior to the first dose with serumfollicle-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: 1. use a condom with spermicide while engaging in sexual activity or be sexually abstinent 2. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study will be the number and severity of treatment emergent adverse events (TEAEs) following single doses of TBA-354 and placebo. | Day 1, 2, 4, 5, 6, 7, 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of TBA-354 in plasma following single oral doses. Cmax, AUC0-24 | Day 1 (Hour 0, 1, 2, 4, 6, 7, 8, 12, 16), Day 2 (Hour 20, 24, 30, 36, 42), Follow up (Hour 72, 96, 120, 144) | Tmax: Time of the maximum drug concentration (obtained without interpolation). Cmax: Maximum observed drug concentration. AUC0-24: Area under concentration time curve 0 to 24 hours |
| Effect of food on the Pharmacokinetics parameters of TBA-354 in plasma following an intermediate single oral dose. Cmax, AUC0-24 | Day 1 (Hour 0, 1, 2, 4, 6, 7, 8, 12, 16), Day 2 (Hour 20, 24, 30, 36, 42), Follow up (Hour 72, 96, 120, 144) | Tmax: Time of the maximum drug concentration (obtained without interpolation). Cmax: Maximum observed drug concentration. AUC0-24: Area under concentration time curve 0 to 24 hours |
| Number of subjects/time points with abnormal findings in safety electrocardiogram | Screening; Day 1 (Hour 0, 1, 2, 4, 6, 8, 12, 16); Day 2 Hour 20, 24, 30, 36 and 48; Follow up Hour 144 | Calculated in terms of QT corrected for heart rate according to Fridericia's corrected formula (QTcF) outliers (QTcF \> 450, \> 480, and \> 500 msec; and change-from-baseline QTcF \> 30 and \> 60 msec). |
| Placebo-corrected safety electrocardiogram Change-from-baseline heart rate | Screening; Day 1 (Hour 0, 1, 2, 4, 6, 8, 12, 16); Day 2 Hour 20, 24, 30, 36 and 48; Follow up Hour 144 | Change-from-baseline heart rate, QT corrected for heart rate according to Fridericia's corrected formula (QTcF), PR, QRS, QT, and incidence of abnormal T-wave morphology from cardiodynamic electrocardiograms extracted from the pre-specified time points. |
Countries
United States
Outcome results
None listed