TGRX-326 Pharmacokinetic Drug Interaction

An Open-label, Two-cycle, Single Sequence, Self-controlled Study Evaluating Effects of Oral Itraconazole or Efavirenz on Pharmacokinetic Profiles of TGRX-326

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.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Itraconazole+TGRX-326; Drug: Efavirenz+TGRX-326

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drug Tower Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole; healthy subjects will be given Itraconazole 200 mg orally with TGRX-326 60 mg	Drug: Itraconazole+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
Experimental: Efavirenz; healthy subjects will be given Efavirenz 600 mg orally with TGRX-326 60 mg	Drug: Efavirenz+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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Tmax	Time to maximum concentration of TGRX-326 measured in plasma	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	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	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	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	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	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 clearance (CL/F)	Apparent clearance of TGRX-326 in plasma	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events/serious adverse events	to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs)	through completion of the study, an average of 1 month
Corrected QT Interval	Corrected QT Interval (QTc) as measured by 12-lead electrocardiogram	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)

Collaborators and Investigators

• Sponsor: Shenzhen TargetRx, Inc.
• Collaborators: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Principal Investigator: Juan Li, MD, Nanjing Drug Tower Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Actual): May 6, 2024
• Study Completion (Actual): May 6, 2024

Study Registration Dates

• First Submitted: February 28, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Itraconazole; Efavirenz
• Other Study ID Numbers: TGRX-326-1003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No