Non Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGItraconazole+TGRX-326
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
DRUGEfavirenz+TGRX-326
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
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Shenzhen TargetRx, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 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 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 |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
Countries
China
Outcome results
None listed