Myelofibrosis
Conditions
Brief summary
Primary objective: To evaluate the effect of rabeprazole on the primary pharmacokinetics of TQ05105 tablets. Secondary objective: To assess the safety and tolerability of single oral administration of TQ05105 tablets alone and in combination with rabeprazole in healthy study participants. To evaluate the effect of rabeprazole on the secondary PK parameters of TQ05105 and the pharmacokinetics of its active metabolite TQ12550.
Interventions
DRUGTQ05105 tablets
TQ05105 tablets are Janus kinase (JAK) inhibitors.
Rabeprazole sodium enteric-coated tablets.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent prior to the study, fully understood the study content, procedures and potential adverse reactions; able to complete the study per protocol requirements. * The participant (including partner) agrees not to plan pregnancy, sperm donation or egg donation from screening until 6 months after the last study drug administration, and is willing to use effective contraception. * Healthy male and female participants aged 18-45 years (inclusive). * Male body weight ≥ 50.0 kg; female body weight ≥ 45.0 kg.BMI = weight (kg)/height² (m²), range 18.0-28.0 kg/m² (inclusive).
Exclusion criteria
* Participants with clinically significant abnormalities in vital signs, physical examination, ECG or clinical laboratory tests, and deemed unsuitable for participation by the investigator. * Participants with severe or chronic diseases of the circulatory, digestive, respiratory, urinary, nervous, hematologic, endocrine/metabolic, neoplastic, immune or psychiatric systems within the past 1 year or currently, or any other disease that may interfere with study results. * Platelet count or absolute neutrophil count below the lower limit of the reference range at screening. * Any disease increasing bleeding risk, such as hemorrhoids, acute gastritis, gastric or duodenal ulcer. * Alanine aminotransferase (ALT) \> 1.2×ULN, aspartate aminotransferase (AST) \> 1.2×ULN, alkaline phosphatase (ALP) \> 1.2×ULN, total bilirubin (TBIL) \> 1.2×ULN, or any clinically significant abnormality judged by the investigator. * Any malignancy within the past 5 years. * Any condition that may affect absorption, distribution, metabolism or excretion of study drug (e.g., inability to swallow), or history of gastrointestinal resection that may affect drug disposition. * Allergy to rabeprazole, TQ05105 or their excipients; or history of multiple allergies (≥2 substances), including drug allergy, and tendency to develop rash, eczema, urticaria, asthma, etc. * Use of any strong or moderate inducers or inhibitors of CYP3A4, CYP2C9 and CYP2C19 within 4 weeks prior to screening. * Use of any prescription drugs, over the counter medications, herbal medicines or dietary supplements (e.g., vitamins, calcium supplements) within 4 weeks prior to screening. * Use of any acid suppressive therapy within 3 months prior to screening. * Participation in any clinical trial involving investigational drugs within 3 months prior to screening or within 5 half lives of the study drug (whichever is longer). * Positive results for HIV antibody, hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV) or syphilis antibody. * Estimated glomerular filtration rate (eGFR) \< 90 mL/min/1.73m² at screening. * Average daily cigarette consumption \>5 cigarettes within 3 months prior to screening. * History of drug abuse within 3 months prior to screening, or positive urine drug screen. * Regular alcohol consumption within 3 months prior to screening (≥14 units/week; 1 unit = 360 mL beer / 45 mL 40% spirits / 150 mL wine), or positive alcohol breath test. * Blood donation or blood loss ≥200 mL, or plasma exchange within 4 weeks prior to screening. * Consumption of alcohol (or positive alcohol breath test), grapefruit juice, coffee, tea, cola, chocolate or related food/beverage within 72 hours before dosing. * Pregnant or breastfeeding female participants, positive serum pregnancy test, or unprotected sexual intercourse within 2 weeks prior to screening for women of childbearing potential. * Strenuous exercise (e.g., marathon, weightlifting) within 2 weeks prior to screening. * Any other condition deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentration (Cmax) | 1 hour before administration, and 10, 20 minutes, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 hours after administration | Maximum plasma drug concentration. |
| Area under the plasma concentration-time curve ( AUC0-t) | 1 hour before administration, and 10, 20 minutes, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 hours after administration | The area enclosed by the blood concentration curve to the timeline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Tmax) | 1 hour before administration, and 10, 20 minutes, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 hours after administration | The time required to reach peak concentration after administration. |
| Plasma clearance (CL/F) | 1 hour before administration, and 10, 20 minutes, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 hours after administration | How much of the plasma is cleared per unit of time. |
| Plasma elimination half-life (t1/2) | 1 hour before administration, and 10, 20 minutes, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 hours after administration | The time it takes for the terminal phase blood concentration to drop by half. |
| Area under the plasma concentration-time curve ( AUC0-∞) | 1 hour before administration, and 10, 20 minutes, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 hours after administration | The area enclosed by the blood concentration curve to the timeline. |
| Adverse event rate | 14 days after the first dose | The occurrence of all adverse events (AEs), and serious adverse events (SAEs). |
| Hematology | 14 days after the first dose | Abnormal hematology |
| Serum biochemistry | 14 days after the first dose | Abnormal serum biochemistry |
| Coagulation | 14 days after the first dose | Abnormal coagulation |
| Urinalysis | 14 days after the first dose | Abnormal urinalysis |
| Blood pressure | 14 days after the first dose | Abnormal blood pressure |
| Pulse | 14 days after the first dose | Abnormal pulse |
| Respiration | 14 days after the first dose | Abnormal respiration |
| Body temperature | 14 days after the first dose | Abnormal body temperature |
| 12-lead ECG | 14 days after the first dose | Abnormal 12-lead ECG |
| Physical examination | 14 days after the first dose | Abnormal physical examination |
| Symptoms | 14 days after the first dose | Abnormal symptoms |
Countries
China
Contacts
CONTACTGuoping Yang, Doctor
CONTACTXiaocong Zuo, Doctor
Outcome results
None listed