Myelofibrosis
Conditions
Brief summary
Primary Objective: To evaluate the effect of single-dose TQ05105 on QTcF interval in healthy Chinese participants. Secondary Objectives: To evaluate the effects of single-dose TQ05105 on other cardiac parameters (heart rate, QT, RR, PR and QRS intervals) in healthy Chinese participants; To verify assay sensitivity by evaluating the effect of moxifloxacin on QTcF interval; To evaluate the safety and tolerability of single-dose TQ05105 in healthy Chinese participants; To characterize the pharmacokinetic (PK) characteristics of TQ05105 and its metabolite (TQ12550) after single administration of TQ05105 tablets in healthy Chinese participants.
Interventions
DRUGTQ05105 tablets
TQ05105 tablets are Janus kinase (JAK) inhibitors.
DRUGPlacebo tablets
Placebo tablets contain no active substance.
Moxifloxacin Hydrochloride Tablets serve as positive control drug.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntarily participate in the clinical trial and sign the informed consent form; fully understand the trial content, procedures and potential adverse reactions; able to communicate well with the investigator and complete the study in accordance with the protocol requirements; 2. Participants (including their partners) have no plans for pregnancy, sperm donation or egg donation from screening until 6 months after the last dose of study drug, and voluntarily adopt effective contraceptive measures; 3. Healthy participants aged 18 to 45 years (inclusive) at the time of signing the informed consent form, both male and female eligible; 4. At screening, male participants weigh no less than 50.0 kg and female participants weigh no less than 45.0 kg. Body mass index (BMI) = weight (kg) / height² (m²), within the range of 18.0 to 26.0 kg/m² (inclusive).
Exclusion criteria
1. History of severe or chronic diseases of the circulatory, digestive, respiratory, urinary, nervous, hematological, endocrine and metabolic, neoplastic, immune or psychiatric systems or any other medical conditions that may interfere with trial outcomes within the past 1 year or at present; 2. History of any malignancy within 5 years before screening; 3. Platelet count or absolute neutrophil count below the lower limit of the reference range in complete blood count at screening; 4. Any condition that increases the risk of bleeding, such as hemorrhoids, acute gastritis, or gastric and duodenal ulcers; 5. Subjects with any condition that may affect the absorption, distribution, metabolism or excretion of the study drug (e.g., inability to swallow tablets) or who have undergone gastrointestinal resection that may interfere with drug absorption, distribution, metabolism or excretion; 6. Risk factors for torsades de pointes (TdP) at screening, including but not limited to the history of: syncope of unknown origin; heart failure; myocardial infarction; angina pectoris; history of various electrolyte abnormalities (potassium, sodium, chloride, calcium, magnesium, etc.); bundle branch block; atrial fibrillation, atrial flutter, atrial premature beats, ventricular premature beats, non-sustained or sustained ventricular tachycardia; bradycardia or sick sinus syndrome; personal or family history of any cardiac conduction abnormality; personal or family history of long QT syndrome (LQTS); or family history of sudden cardiac death; 7. Hypersensitivity to moxifloxacin or any fluoroquinolone antibacterial agents, TQ05105 or its excipients, or history of multiple allergies (e.g., allergy to two or more substances, including drug allergy history, predisposition to skin rash, eczema, urticaria, asthma, etc.); 8. Use of any strong or moderate inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 enzymes within 4 weeks before screening (see Appendix 3 for details); 9. Use of any prescription drugs (including that may cause QT/QTc interval prolongation / TdP), over-the-counter drugs, Chinese herbal medicines or dietary supplements (e.g., vitamins, calcium supplements, etc.) within 4 weeks before screening; 10. Participation in any drug clinical trial and exposure to any investigational product within 3 months before screening or within 5 half-lives of the drug (whichever is longer); 11. Abnormal results of physical examination, vital signs, clinical laboratory tests (complete blood count, blood biochemistry, coagulation function, urinalysis), chest radiograph (PA and lateral views), or abdominal ultrasound (liver, gallbladder, pancreas, spleen and kidneys) at screening that are judged clinically significant by the investigator; 12. 12-lead ECG exceeding the following thresholds at screening or baseline: PR \> 200 ms, QRS \> 110 ms, HR \< 50 bpm or \> 100 bpm, QTcF \> 450 ms (for both males and females); or ECG abnormalities judged by the investigator to be clinically significant (e.g., atrioventricular block, torsades de pointes, other types of ventricular tachycardia, ventricular fibrillation and ventricular flutter, clinically significant T-wave changes, or any 12-lead ECG abnormalities that may affect the QTc interval); 13. Positive test results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or Treponema pallidum antibody; 14. Glomerular filtration rate (eGFR) \< 90 mL/min/1.73m² at screening; 15. Average daily cigarette consumption of more than 5 cigarettes within 3 months before screening; 16. History of substance abuse within 3 months before screening, or positive urine drug screen; 17. Regular alcohol consumption within 3 months before screening, defined as more than 14 standard alcohol units per week (1 unit = 360 mL beer, or 45 mL spirits with 40% alcohol content, or 150 mL wine), or positive breath alcohol test; 18. Blood donation or blood loss ≥ 200 mL, or plasmapheresis within 4 weeks before screening; 19. Consumption of any food or beverage containing alcohol (or positive breath alcohol test), grapefruit juice, coffee, tea, cola, or chocolate within 72 hours before dosing; 20. Pregnant or lactating female participants, or positive blood pregnancy test or value above the upper limit of normal, or female participants of childbearing potential who have had unprotected sexual intercourse within 2 weeks before screening; 21. Strenuous exercise (e.g., marathon, weightlifting) within 2 weeks before screening; 22. Any other condition considered by the investigator to make the participant unsuitable for the trial; 23. Participants unable to complete the trial due to personal reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fridericia Placebo-Corrected Change from Baseline in QTc Interval (ΔΔQTcF) | 60 minutes, 45 minutes and 30 minutes before dosing on Day 1 of each period, and 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | Placebo \& baseline corrected ΔQTcF, core indicator to assess drug effect on ventricular repolarization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate (HR) | 60 minutes, 45 minutes and 30 minutes before dosing on Day 1 of each period, and 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | Holter-derived heart rate |
| PR interval (PR) | 60 minutes, 45 minutes and 30 minutes before dosing on Day 1 of each period, and 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | PR interval obtained via continuous Holter ECG monitoring |
| RR interval (RR) | 60 minutes, 45 minutes and 30 minutes before dosing on Day 1 of each period, and 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | Holter-recorded RR interval |
| Peak concentration (Cmax) | 1 hours before dosing, and at 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | Maximum plasma drug concentration |
| Area under the plasma concentration-time curve ( AUC0-t) | 1 hours before dosing, and at 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | The area enclosed by the blood concentration curve to the timeline |
| Plasma clearance (CL/F) | 1 hours before dosing, and at 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | How much of the plasma is cleared per unit of time |
| Plasma elimination half-life (t1/2) | 1 hours before dosing, and at 15 minutes, 30 minutes, 1 hours, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours after dosing. | The time it takes for the terminal phase blood concentration to drop by half |
| Adverse event rate | 26 days after the first dose | The occurrence of all adverse events (AEs), and serious adverse events (SAEs). |
| Hematology | 26 days after the first dose | Abnormal hematology |
| Serum biochemistry | 26 days after the first dose | Abnormal serum biochemistry |
| Coagulation | 26 days after the first dose | Abnormal coagulation |
| Urinalysis | 26 days after the first dose | Abnormal urinalysis |
| Blood pressure | 26 days after the first dose | Abnormal blood pressure |
| Pulse | 26 days after the first dose | Abnormal pulse |
| Body temperature | 26 days after the first dose | Abnormal body temperature |
Countries
China
Contacts
CONTACTJie Hou, Doctor
CONTACTXiaoyu Zhang, Master
Outcome results
None listed