The purpose of this study is to assess the safety, tolerability and pharmacokinetics (i.e. how study drug is taken up by the body) of TBN in healthy participants.
The trial is a single center, placebo-controlled, double-blind, multiple-dose study in 2 ascending dose cohorts of healthy subjects. The primary purpose of this study is to investigate the safety, tolerability and pharmacokinetic property of the multiple doses of TBN administered for 6.5 consecutive days in healthy participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
16
Subjects will be administered multiple oral doses of TBN or matching placebo tablets twice a day for 6 consecutive days and a last dose in the morning of Day 7.
Number of participants with Adverse Events (AEs)
The number and severity of AEs will be graded according to criteria from the NCI-CTCAE (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management).
Time frame: 14 days
Assessment of physical examination.
Physical examination will be assessed on Day-1, Day4, and check-out (Day8), follow-up visit (Day14±2).
Time frame: 14 days
Assessment of vital signs.
Vital signs, including orthostatic blood pressure and heart rate, respiratory rate and oral temperature, will be evaluated from Day-1 to check-out (Day8), and at follow-up visit (Day14±2).
Time frame: 14 days
Assessment of 12 lead-ECG.
12 lead-ECG will be assessed on Day-1, Day4, Day 7 and at check-out (Day8), follow-up visit (Day14±2).
Time frame: 14 days
Assessment of urine pregnancy.
Urine pregnancy test will be assessed on Day-1 and at follow-up visit (Day14±2).
Time frame: 14 days
Assessment of Clinical Laboratory Tests.
Clinical laboratory tests includes hematology, clinical chemistry, coagulation (prothrombin time and partial thromboplastin time), endocrinology (T3, T4, and thyroid stimulating hormone) and urinalysis, will be assessed on Day-1, Day2, Day4, Day6 and at check-out (Day8), follow-up visit (Day14±2).
Time frame: 14 days
Maximum observed concentration (Cmax) of TBN and its metabolite.
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Plasma concentrations of TBN and its metabolite \[Time point: pre-dose, 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 (prior to the second dose)\], and derived pharmacokinetic parameters Cmax.
Time frame: 0 to 12 hours after on the morning dosing of the first day
Time of occurrence of Cmax (Tmax) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: pre-dose, 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 (prior to the second dose)\], and derived pharmacokinetic parameters Tmax.
Time frame: 0 to 12 hours after on the morning dosing of the first day
Area under the concentration-time curve from time zero to time 12 hours (AUC0-12) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: pre-dose, 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 (prior to the second dose)\], and derived pharmacokinetic parameters AUC0-12.
Time frame: 0 to 12 hours after on the morning dosing of the first day
Lowest concentration before the next dose is administered (Ctrough) of TBN and its metabolite.
Time point: pre-morning dose of Day2, Day3, Day4, Day5 and Day6.
Time frame: From Day2 to Day6
Area under the concentration-time curve for one dosing interval (12 hours) at steady-state (AUC0-tau) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters AUC0-tau.
Time frame: 0-24 hours after the last dose at Day7
Average drug concentration calculated at AUC0-tau/tau (Caverage) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: Time frame: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters Caverage.
Time frame: 0-24 hours after the last dose at Day7
Minimum observed concentration at steady-state (Cmin_ss) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: Time frame: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters Cmin\_ss.
Time frame: 0-24 hours after the last dose at Day7
Area under the concentration-time curve from time zero to the 24 hours concentration (AUC0-24) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: Time frame: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters AUC0-24.
Time frame: 0-24 hours after the last dose at Day7
Maximum observed concentration at steady-state (Cmax_ss) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: Time frame: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters Cmax\_ss.
Time frame: 0-24 hours after the last dose at Day7
Time of observed Cmax_ss (Tmax_ss) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: Time frame: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters Tmax\_ss.
Time frame: 0-24 hours after the last dose at Day7
Area under the concentration-time curve from time zero to infinity (AUC0-inf) of TBN and its metabolite.
Plasma concentrations of TBN and its metabolite \[Time point: Time frame: pre-dose, and 1, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, and 24 hours after the last dose at Day7\], and derived pharmacokinetic parameters AUC0-inf.
Time frame: 0-24 hours after the last dose at Day7