Chronic Myeloid Leukemia
Conditions
Brief summary
This is a pharmacokinetic study for \[14C\]TGRX-678 on mass balance to evaluate distribution, metabolism and excretion of TGRX-678, a tyrosine kinase inhibitor indicated for treatment of chronic myeloid leukemia.
Detailed description
This study is designed as a single-center, single-dose, non-randomized and open-label study. The study will be conducted in healthy male participants to evaluate distribution, metabolic pathways and route of excretion of TGRX-678 using the Carbon-14 labelled isotope of TGRX-678 compound. Safety and pharmacokinetic evaluation will also be conducted.
Interventions
DRUG[14C]TGRX-678
Healthy subjects will be given TGRX-678 240 mg orally on day 1.
Sponsors
The First Affiliated Hospital of Soochow University
Shenzhen TargetRx, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult males * age between 18 and 45 (both included) years old * body weight index between 19.0 and 26.0 kg/m2 (both included, and body weight not lower than 50 kg * can volunteeringly consent * can communicate well with investigators and complete study according to protocol requirements
Exclusion criteria
* abnormal and of clinical significance results on physical exam, regular laboratory tests, thyroid function, anal check, chest x-ray, abdominal ultrasound check or 12-lead ECG * positive test results on hepatitis B surface antigen/ E antigen, hepatitis C antibody, HIV antigen/antibody or syphylus antibody * abnornal and of clinical significance results on eye exam * usage of any inducers or inhibitors for drug metabolism enzymes (especially CYP3A4) within 30 days of screening * usage of any prescriptional drug, OTC drug, herbal medicine, traditional Chinese medicine, or food supplements (i.e., vitamins, calcium) within 14 days of screening * history of any clinically significant serious diseases or any conditions that at investigator's discretion may affect study results * have condition that may affect drug absoption * received major surgery or with un-healed surgical wounds within 6 months of screening * have allergies to at least 2 substances or at investigator's discretion may be allergic to investigational drug or any excipients * have hemorrhoids; have history of or is having conditions that cause bloody feces, irritable bowel syndrome, or inflammatory bowel disease * habitutory constipation or diarrhea * alcohol abuse, or frequent use of alcohol within 6 months of screening * smoking of more than 5 cigarettes per day within 3 months of screening, or habitutory use of nicotine products and cannot quit during study * drug abuse, or use of soft drug (marajuana) within 3 months of screening, or use of hard drug (phenylamine or PCP type drugs) within 1 year of screening, or tested positive in urine drug test during screening * habitutory use of grape fruit juice, or overuse of tea, coffee or caffeinated drugs, and cannot quit during study * long-term occupational exposure to radioactive conditions, or have history of significant radioactive substance exposure or participated in clinical study using radioactive-labeled drugs within 1 year of current study * Having difficulties to receive venous needle puncture, or cannot tolerate venous needle puncture, or history of hematophobia or needle sickness * Participation in any other clinical studies within 3 months before screening * Reception of vaccine within 1 months before screening, or planning to be vaccinated during the study * Planning to have children or donate sperms during the study and within 1 year after the study, or Not agreeing to take contraceptive measures during and within 1 year after study completion * Blood donation or blood loss of \> 400 ml within 3 months before screening; blood donation or blood loss of \> 200 ml within 1 month before screening; reception of blood transfusion within 1 months before screening; received blood donation within 1 months of study, or planning to donate blood within 3 months after study completion * Having special dietary requirements and unable to follow the uniform dietary plan in the study * Any conditions that the investigator deemed unfit for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma AUC(0-t) | Day-1 (day before dosing), Day 1 to Day 54 after dosing | Area under curve for TGRX-678 plasma concentration from before dose to last measureable timepoint |
| Urine radioactivity | Day-1 (day before dosing), Day 1 to Day 54 after dosing | \[C14\]TGRX-678 radioactivity detected in urine |
| Fecal radioactivity | Day-1 (day before dosing), Day 1 to Day 54 after dosing | \[C14\]TGRX-678 radioactivity detected in feces |
| Plasma AUC (Area under curve) percentage | Day-1 (day before dosing), Day 1 to Day 54 after dosing | percentage of \[C14\]TGRX-678 radioactivity in plasma |
| Urine %Dose | Day-1 (day before dosing), Day 1 to Day 54 after dosing | percentage of \[C14\]TGRX-678 radioactivity in urine |
| Fecal %Dose | Day-1 (day before dosing), Day 1 to Day 54 after dosing | percentage of \[C14\]TGRX-678 radioactivity in feces |
| Plasma Cmax | Day-1 (day before dosing), Day 1 to Day 54 after dosing | Maximum concentration of \[C14\]TGRX-678 measured in plasma |
| Plasma Tmax | Day-1 (day before dosing), Day 1 to Day 54 after dosing | Time to maximum concentration of \[C14\]TGRX-678 measured in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events/serious adverse events | Day-1 (day before dosing), Day 1 to Day 54 after dosing or the day sample collection is completed | to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs) |
Countries
China
Outcome results
None listed