TGRX-326 Phase I/II Pharmacokinetic Study

A Randomized, Open-label, Single-dose, 3-cycle, 6-sequence, Crossover Study Evaluating Food Effect on Pharmacokinetic Profiles of TGRX-326 in Chinese Healthy Subjects and Effect of Drug Specification on Bioavailability in Human

A study evaluating the effects of food intake on the pharmacokinetic (PK) profiles of TGRX-326 and the effect of different drug specifications on human bioavailability for TGRX-326, a drug indicated for non-small cell lung cancer treatment

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: cycle 1: treatment drug; Behavioral: cycle 1: fasted; Drug: cycle 2: reference drug; Behavioral: cycle 2: fasted; Drug: cycle 3: treatment drug; Behavioral: cycle 3: food; Drug: cycle 1: reference drug; Drug: cycle 2: treatment drug; Behavioral: cycle 2: food; Behavioral: cycle 3: fasted; Behavioral: cycle 1: food; Drug: cycle 3: reference drug

Detailed Description

This study is designed as single-center, randomized, open-label, 3-cycle, 6-sequence and crossover design to evaluate 1) food effect on PK profile of TGRX-326; 2) effect of different specifications of TGRX-326 on human bioavailability. Safety for food effect on TGRX-326 and safety for different TGRX-326 specifications were also evaluated.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • First Affiliated Hospital Bengbu Medical College

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• able to understand the purpose, methods and possible adverse events of the study and agree to volunteering consent before the start of study
• healthy subject; male or female
• Age between 18 and 55 (inclusive)
• body mass index (BMI) between 19.0 and 26.0 (inclusive), male weight <=50 kg, female weight <=45 kg
• normal/ clinically insignificant test results (including physical exam, laboratory tests, 12-lead ECG, chest x-ray, etc.)
• participant/partner of the participant does not have plans for child bearing from screening until 6 months after study, and is willing to take contraceptive measures during study period and for 6 months, and does not have plans to donate sperm/egg during the said period

Exclusion Criteria:

• history of allergic reactions, or allergic to any components to the study drugs that by investigator's judgement unsuitable for the study
• any clinically significant conditions that could affect study outcomes, safety or compliance
• history of major surgery within 3 months before first dose, or have plans to receive surgery during the study, or history of any surgery that could affect drug absorption, distribution, metabolism and excretion
• have difficulties to receive venous needle puncture, or cannot tolerate venous needle puncture, or history of hematophobia or needle sickness
• history of substance abuse
• have special food requirement or cannot follow food requirement of the study, or lactose intolerant
• use of any investigational drug or participation of any clinical study (for drug or medical device) within 3 months before first dose, or cannot participate the study in person/on site
• history of blood donation, blood loss (>= 400 mL, excluding normal blood loss during female menstrual period), or reception of blood transfusion within 3 months before screening
• history of 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 cannot avoid alcohol consumption during study
• history of large tea/coffee/caffeinated drink intake (more than 8 cups per day) within 3 months before first dose
• history of irregular dietary schedule within 1 months of first dose (including, dieting, overeating, low sodium intake, etc.)
• use of any prescription / over-the-counter drug, or Chinese herbal medication, or health supplementary products within 14 days of test article administration
• vaccination within 14 days before first test article administration, or have plans to receive vaccination during the study period
• any one positive result for hepatitis-B surface antigen, Hepatitis C antibody, HIV antibody or syphilis antibody
• alcohol breathing test results of > 0.0 mg/100mL for blood alcohol concentration
• positive test results on substance use (including, morphine, methylamphetamine, ketamine, tetrahydrocannabinol, methylene-dioxy-methyl-amphetamine)
• female in pregnancy or breastfeeding period, or positive pregnancy test result
• history of unprotected sexual activities within 14 days before first dose
• consumption of food or drink rich in caffeine/xanthine (such as chocolate, coffee, tea, coke) or food/food product of grapefruit, dragon fruit, mango, tangerine, or any food that could affect drug absorption, distribution, metabolism and excretion
• 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: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; cycle 1: treatment drug + fasted cycle 2: reference drug + fasted cycle 3: treatment drug + food	Drug: cycle 1: treatment drug; for cycle 1 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 1: fasted; for cycle 1 treatment: participants are asked to take the drug fasted; Drug: cycle 2: reference drug; for cycle 2 treatment: participants are given the oral reference specification (5 mg *2 pills + 25 mg * 2 pills); Behavioral: cycle 2: fasted; for cycle 2 treatment: participants are asked to take the drug fasted; Drug: cycle 3: treatment drug; for cycle 3 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 3: food; for cycle 3 treatment: participants are asked to take the drug after food intake
Experimental: Group B; cycle 1: reference drug + fasted cycle 2: treatment drug + food cycle 3: treatment drug + fasted	Behavioral: cycle 1: fasted; for cycle 1 treatment: participants are asked to take the drug fasted; Drug: cycle 3: treatment drug; for cycle 3 treatment: participants are given the oral treatment specification (60 mg *1 pill); Drug: cycle 1: reference drug; for cycle 1 treatment: participants are given the oral reference specification (5 mg *2 pills + 25 mg * 2 pills); Drug: cycle 2: treatment drug; for cycle 2 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 2: food; for cycle 2 treatment: participants are asked to take the drug after food intake; Behavioral: cycle 3: fasted; for cycle 3 treatment: participants are asked to take the drug fasted
Experimental: Group C; cycle 1: treatment drug + food cycle 2: treatment drug + fasted cycle 3: reference drug + fasted	Drug: cycle 1: treatment drug; for cycle 1 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 2: fasted; for cycle 2 treatment: participants are asked to take the drug fasted; Drug: cycle 2: treatment drug; for cycle 2 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 3: fasted; for cycle 3 treatment: participants are asked to take the drug fasted; Behavioral: cycle 1: food; for cycle 1 treatment: participants are asked to take the drug after food intake; Drug: cycle 3: reference drug; for cycle 3 treatment: participants are given the oral reference specification (5 mg *2 pills + 25 mg * 2 pills)
Experimental: Group D; cycle 1: treatment drug + food cycle 2: reference drug + fasted cycle 3: treatment drug + fasted	Drug: cycle 1: treatment drug; for cycle 1 treatment: participants are given the oral treatment specification (60 mg *1 pill); Drug: cycle 2: reference drug; for cycle 2 treatment: participants are given the oral reference specification (5 mg *2 pills + 25 mg * 2 pills); Behavioral: cycle 2: fasted; for cycle 2 treatment: participants are asked to take the drug fasted; Drug: cycle 3: treatment drug; for cycle 3 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 3: fasted; for cycle 3 treatment: participants are asked to take the drug fasted; Behavioral: cycle 1: food; for cycle 1 treatment: participants are asked to take the drug after food intake
Experimental: Group E; cycle 1: reference drug + fasted cycle 2: treatment drug + fasted cycle 3: treatment drug + food	Behavioral: cycle 1: fasted; for cycle 1 treatment: participants are asked to take the drug fasted; Behavioral: cycle 2: fasted; for cycle 2 treatment: participants are asked to take the drug fasted; Drug: cycle 3: treatment drug; for cycle 3 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 3: food; for cycle 3 treatment: participants are asked to take the drug after food intake; Drug: cycle 1: reference drug; for cycle 1 treatment: participants are given the oral reference specification (5 mg *2 pills + 25 mg * 2 pills); Drug: cycle 2: treatment drug; for cycle 2 treatment: participants are given the oral treatment specification (60 mg *1 pill)
Experimental: Group F; cycle 1: treatment drug + fasted cycle 2: treatment drug + food cycle 3: reference drug + fasted	Drug: cycle 1: treatment drug; for cycle 1 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 1: fasted; for cycle 1 treatment: participants are asked to take the drug fasted; Drug: cycle 2: treatment drug; for cycle 2 treatment: participants are given the oral treatment specification (60 mg *1 pill); Behavioral: cycle 2: food; for cycle 2 treatment: participants are asked to take the drug after food intake; Behavioral: cycle 3: fasted; for cycle 3 treatment: participants are asked to take the drug fasted; Drug: cycle 3: reference drug; for cycle 3 treatment: participants are given the oral reference specification (5 mg *2 pills + 25 mg * 2 pills)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Cmax	Maximum concentration of TGRX-326 measured in plasma	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
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	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
Plasma AUC(0-inf)	Area Under drug concentration-time curve from time 0 to infinity for TGRX-326 as measured in plasma	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Tmax	Time to maximum concentration of TGRX-326 measured in plasma	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
terminal elimination rate constant (lambda-z)	terminal elimination rate constant calculated from plasma TGRX-326 concentrations	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
Elimination half-life (T1/2-Z)	Time for TGRX-326 to decrease from maximum plasma concentration to half of maximum plasma concentration	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
AUC(%Extrap)	Calculated percentage of Area under curve for AUC(0-inf) that is from last measurable timepoint ot infinity, calculated based on TGRX-326 plasma concentration over time curve.	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
Plasma volume of distribution (Vz/F)	Apparent volume of distribution of TGRX-326 in plasma	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
Plasma clearance (CL/F)	Apparent clearance of TGRX-326 in plasma	During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles)
Adverse events/serious adverse events	to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs)	through completion of the study, a total duration of 37 days

Collaborators and Investigators

• Sponsor: Shenzhen TargetRx, Inc.
• Collaborators: First Affiliated Hospital Bengbu Medical College
• Investigators: Principal Investigator: Huan Zhou, MD, First Affiliated Hospital Bengbu Medical College

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Actual): January 12, 2024
• Study Completion (Actual): January 19, 2024

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 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
• Other Study ID Numbers: TGRX-326-1002

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