TGRX-326 Pharmacokinetic Drug Interaction
- Conditions
- Non Small Cell Lung Cancer
- Interventions
- Drug: Efavirenz+TGRX-326Drug: Itraconazole+TGRX-326
- Registration Number
- NCT06294561
- Lead Sponsor
- Shenzhen TargetRx, Inc.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- healthy subject; male or female
- Age between 18 and 45 (inclusive)
- body mass index (BMI) between 19.0 and 26.0 (inclusive)
- agree to consent
- able to communicate with investigator well and complete the study according to study protocol
- abnormal and clinically significant test results (including physical exam, laboratory tests, 12-lead ECG, chest x-ray, etc.)
- any one positive result for hepatitis-B surface antigen, Hepatitis C antibody, HIV antibody or syphilis antibody
- prolongation in QT interval
- use of substance that affects CYP3A4 enzyme activity with 30 days before screening
- use of any drug within 14 days of test article administration
- use of any investigational drug or participation of any clinical study within 3 months before screening
- vaccination within 14 days before first test article administration, or have plans to receive vaccination during the study period
- history of cardiovascular diseases
- history of mental conditions including depression, aggressive behaviours, epilepsy, etc.
- history of major surgery within 6 months before screen, or have unhealed surgical wounds.
- any clinically significant conditions that investigator believes could affect study outcomes
- history of allergic reactions, or allergic to any components to the study drugs, or have food allergy/special requirement for food that forbids the subject to follow food requirements for the study
- daily cigarette consumption of more than 5 within 3 months before screening, or cannot avoid using cigarette/tabacco products during the study
- history of alcohol abuse (more than 14 units of alcohol per week) within 3 months before screening, or alcohol breath test of > 0.0 mg/dl at screening
- history of substance abuse, or positive drug results at screening
- history of certain food intake 2 weeks before screening, and/or use of more than 8 cups of tea/coffee/grapefruit juice
- positive pregnancy test results, or pregnant/breast-feeding females
- history of unprotected sexual activities within 1 month before screening
- have plans for child bearing during study period and for 6 months after study, or disagree to take contraceptive measures during study period and for 6 months after study
- history of blood donation or blood loss within 3 months before screening, or have plans to donate blood within 1 month after the study
- any reasons that is deemed unsuitable for study participation as determined by investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Efavirenz Efavirenz+TGRX-326 healthy subjects will be given Efavirenz 600 mg orally with TGRX-326 60 mg Itraconazole Itraconazole+TGRX-326 healthy subjects will be given Itraconazole 200 mg orally with TGRX-326 60 mg
- Primary Outcome Measures
Name Time Method Plasma Tmax 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) Time to maximum concentration of TGRX-326 measured in plasma
Plasma AUC(0-t) 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) Area Under drug concentration-time curve (AUC) from time 0 to last measureable timepoint for TGRX-326 as measured in plasma
T1/2 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 half-life of TGRX-326
Plasma AUC(0-inf) 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) Area Under drug concentration-time curve from time 0 to infinity for TGRX-326 as measured in plasma
Plasma volume of distribution (Vz/F) 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) Apparent volume of distribution of TGRX-326 in plasma
Plasma clearance (CL/F) 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) Apparent clearance of TGRX-326 in plasma
Plasma Cmax 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) Maximum concentration of TGRX-326 measured in plasma
- Secondary Outcome Measures
Name Time Method Adverse events/serious adverse events through completion of the study, an average of 1 month to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs)
Corrected QT Interval 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) Corrected QT Interval (QTc) as measured by 12-lead electrocardiogram
Trial Locations
- Locations (1)
Nanjing Drug Tower Hospital
🇨🇳Nanjing, Jiangsu, China