TGRX-326 Pharmacokinetic Drug Interaction

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06294561
• Other study ID #: TGRX-326-1003
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2024
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2024
• Source: Shenzhen TargetRx, Inc.
• Contact: Juan Li, MD
• Phone: +86-025-83105910
• Email: juanli2003[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: June 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Intervention

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
• 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

Locations

Country	Name	City	State
China	Nanjing Drug Tower Hospital	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Shenzhen TargetRx, Inc.	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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)