Effect of Omeprazole on the Pharmacokinetics of SHR6390 in Healthy Subjects

Study Overview
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Brief Summary
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This is a one-arm, fixed-sequence study to compare the pharmacokinetic profiles of SHR6390 in absence and presence of prior administration of proton pump inhibitor Omeprazole. The increased gastric pH achieved by the treatment with multiple doses of Omeprazole might affect the absorption process of SHR6390.

Official Title
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A Single-centre, One-arm, Open-label, Fixed-sequence Study to Evaluate the Effect of Omeprazole on the Pharmacokinetics of SHR6390 in Healthy Male and Female Subjects

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: SHR6390、Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions; Ability to complete the study as required by the protocol; Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent; Subjects shall ake effective contraceptive measures voluntarily within 7 months from the date of signing the informed consent form to the date of the last medication. Serum HCG test of fertile women before the study must be negative; Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI) within the range of 19   26 kg /m2 (including 19 and 26); Healthy subjects identified by a detailed medical history; Full physical examinations, including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory test, are normal or abnormal but have no clinical significance. Exclusion Criteria: Blood donation or loss≥400 mL within 3 months prior to screening, or blood donation or loss≥200 mL, or blood transfusion within 1 months before screening; Participating in any clinical trial or taking drugs that might damage organs within 3 months before screening; Surgeries in the previous 6 months before screening; Use of vaccines or biologicals within 2 weeks prior to screening; Allergic constitution; History of drug abuse or alcoholism, or positive for nicotine, alcohol and drug tests; History of myocarditis, coronary heart disease, arrhythmia, stroke and so on, or 12 lead ECG demonstrating a corrected QT by Fridericia (QTcF) interval ≥450 msec; With dysphagia or history of gut disease or surgery (gastrectomy, enterectomy, sleeve gastrectomy, etc) possibly affecting drug absorption; Uncontrolled gut disease, such as peptic ulcer, colitis, pancreatitis, etc; History of chronic kidney disease, renal insufficiency, anemia of renal failure, or creatinine clearance rate (CLCr) < 80 mL/min, or serum creatinine ≥ ULN.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: The study is a single-center, open, single-dose, Fixed-sequence clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br> | Drug: SHR6390、Omeprazole<br>* SHR6390 tablet single dose、Omeprazol single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed serum concentration (Cmax) for SHR6390 after Single dose. | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 
| AUC0-t | Area under the plasma concentration versus time curve (AUC0-t) for SHR6390 after Single dose | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 
| AUC0-∞ | Area under the plasma concentration versus time curve (AUC0-∞) for SHR6390 after Single dose | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to maximum observed serum concentration (Tmax) for SHR6390 after Single dose | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 
| T1/2 | Time to elimination half-life (T1/2) for SHR6390 after Single dose.[Time Frame | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 
| CL/F | Apparent oral clearance (CL/F) for SHR6390 after Single dose | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 
| Vz/F | Apparent Volume of Distribution (Vz/F) SHR6390 after Single dose | from Day1 to Day7after the first dose and from Day17 to Day23 after the second dose | 
| Number of subjects with adverse events and severity of adverse events |  | from Day1 to Day30 after the first dose |