Clinical trial NCT06294561: TGRX-326 Pharmacokinetic Drug Interaction
Official title: An Open-label, Two-cycle, Single Sequence, Self-controlled Study Evaluating Effects of Oral Itraconazole or Efavirenz on Pharmacokinetic Profiles of TGRX-326
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Shenzhen TargetRx, Inc.
Sponsor class: INDUSTRY
Collaborators: name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
First posted: 2024-03-05
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma Tmax
timeFrame: 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)
measure: Plasma Cmax
timeFrame: 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)
measure: Plasma AUC(0-t)
timeFrame: 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)
measure: Plasma AUC(0-inf)
timeFrame: 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)
measure: T1/2
timeFrame: 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)
measure: Plasma volume of distribution (Vz/F)
timeFrame: 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)
measure: Plasma clearance (CL/F)
timeFrame: 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)
Secondary outcomes:
measure: Adverse events/serious adverse events
timeFrame: through completion of the study, an average of 1 month
measure: Corrected QT Interval
timeFrame: 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)
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Drug Tower Hospital
state: Jiangsu
Study officials:
affiliation: Nanjing Drug Tower Hospital
name: Juan Li, MD
role: PRINCIPAL_INVESTIGATOR
References: