This is a drug-drug interaction study for TGRX-326 to evaluate the effects of CYP3A inhibitor/inducer drugs on pharmacokinetic profiles of TGRX-326, an ALK inhibitor indicated for treatment of Non-small cell lung cancer.
This study is designed as an open-label, single sequence, self-controlled study. The study will be conducted for 2 cycles, 10 days per cycle. Itraconazole, a CYP3A inhibitor, and Efavirenz, a CYP3A inducer, will be administrated orally with TGRX-326 to evaluate the effect of these drugs on the pharmacokinetic profiles of TGRX-326. Pharmacokinetic parameters will be evaluated as primary endpoints. Safety evaluation will also be conducted.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
healthy subjects will be given TGRX-326 60 mg orally on Day 1, and Itraconazole 200 mg with TGRX-326 60 mg orally on day 11
healthy subjects will be given TGRX-326 60 mg orally on Day 1, and Efavirenz 600 mg with TGRX-326 60 mg orally on day 20
Nanjing Drug Tower Hospital
Nanjing, Jiangsu, China
Plasma Tmax
Time to maximum concentration of TGRX-326 measured in plasma
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Plasma Cmax
Maximum concentration of TGRX-326 measured in plasma
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Plasma AUC(0-t)
Area Under drug concentration-time curve (AUC) from time 0 to last measureable timepoint for TGRX-326 as measured in plasma
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Plasma AUC(0-inf)
Area Under drug concentration-time curve from time 0 to infinity for TGRX-326 as measured in plasma
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
T1/2
Plasma half-life of TGRX-326
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Plasma volume of distribution (Vz/F)
Apparent volume of distribution of TGRX-326 in plasma
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
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Plasma clearance (CL/F)
Apparent clearance of TGRX-326 in plasma
Time frame: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Adverse events/serious adverse events
to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs)
Time frame: through completion of the study, an average of 1 month
Corrected QT Interval
Corrected QT Interval (QTc) as measured by 12-lead electrocardiogram
Time frame: At screening; Itraconazole group: Day 1, Days 2-5, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Day 20 and Day 25 (or last day of dosing)