Effect of Omeprazole on the Pharmacokinetics of SHR6390 in Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: SHR6390、Omeprazole

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Shanghai Xuhui Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions;
2. Ability to complete the study as required by the protocol;
3. Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent;
4. 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;
5. 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);
6. Healthy subjects identified by a detailed medical history;
7. 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:

1. 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;
2. Participating in any clinical trial or taking drugs that might damage organs within 3 months before screening;
3. Surgeries in the previous 6 months before screening;
4. Use of vaccines or biologicals within 2 weeks prior to screening;
5. Allergic constitution;
6. History of drug abuse or alcoholism, or positive for nicotine, alcohol and drug tests;
7. 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;
8. With dysphagia or history of gut disease or surgery (gastrectomy, enterectomy, sleeve gastrectomy, etc) possibly affecting drug absorption;
9. Uncontrolled gut disease, such as peptic ulcer, colitis, pancreatitis, etc;
10. History of chronic kidney disease, renal insufficiency, anemia of renal failure, or creatinine clearance rate (CLCr) < 80 mL/min, or serum creatinine ≥ ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group	Drug: SHR6390、Omeprazole; SHR6390 tablet single dose、Omeprazol single dose.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2021
• Primary Completion (Actual): January 26, 2022
• Study Completion (Actual): February 14, 2022

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: SHR6390-I-113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No