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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
48
Celerion
Lincoln, Nebraska, United States
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.
Time frame: Day 1, 2, 4, 5, 6, 7, 14
Pharmacokinetics of TBA-354 in plasma following single oral doses. Cmax, AUC0-24
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
Time frame: 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)
Effect of food on the Pharmacokinetics parameters of TBA-354 in plasma following an intermediate single oral dose. Cmax, AUC0-24
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
Time frame: 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)
Number of subjects/time points with abnormal findings in safety electrocardiogram
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).
Time frame: 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
Placebo-corrected safety electrocardiogram Change-from-baseline heart rate
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.
Time frame: 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
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