A Rifampin Effect Study of SHR2554 on Healthy Chinese Adult Subjects

A Single-center, Open, Single Does, Drug-drug Interaction Study to Investigate the Effects of Rifampin on the Pharmacokinetics of Healthy Chinese Adult Subjects After Oral Administration of SHR2554 Tablets

The primary objective of the study is to evaluate the effect of Rifampin on pharmacokinetics of healthy Chinese adult subjects after oral administration of SHR2554 tablets. The secondary objective of the study is to evaluate the safety of single-dose oral administration of SHR2554 in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: SHR2554 and Rifampin

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Jiangsu HengRui Medicine Co., Ltd.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The informed consent is signed before the trial, and the content, process and possible adverse reactions are fully understood;
2. Be able to complete the study according to the requirements of the test scheme;
3. Healthy male and female subjects aged 18 to 45 years (including both ends) on the date of signing informed consent;
4. The body weight of male subjects is no less than 50 kg and that of female subjects is no less than 45 kg. Body mass index (BMI) is in the range of 19.0-26.0 kg/m2 (including the critical value).

Exclusion Criteria:

1. Participated in blood donation within 3 months before taking the study drug and donate blood ≥400 mL, or received blood transfusion;
2. Allergic constitution, including severe drug allergy or drug allergy history; allergic history of SHR2554 tablets, Rifampin, Rifamycin or their excipients;
3. People who have a history of drug and/or alcohol abuse, have a positive alcohol or drug screening test, or have a history of drug abuse in the past five years or have used drugs within 3 months before the test;
4. Smoking and alcohol addicts (drinking 14 units of alcohol per week: 1 unit = 285 ml beer, 25 ml spirits, or 100 ml wine; smoking ≥ 5 cigarettes a day) and unable to prohibit smoking and alcohol during the test period;
5. Comprehensive physical examination (vital signs, physical examination), routine laboratory examinations (blood routine, blood biochemistry, urine routine, etc.), 12-lead electrocardiogram, chest X-ray, heart color Doppler ultrasound, etc. are abnormal and have clinical significance as judged by the investigator;
6. Echocardiography suggests that the left ventricular ejection fraction (LVEF) is less than 50% or the QT interval (QTcF) corrected by Fridericia method in 12-lead ECG is ≥ 470msec;
7. A clear medical history of primary diseases of important organs such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and musculoskeletal system, etc., the investigator considers not suitable for participating in this study;
8. Those who have undergone any surgery within 6 months before screening;
9. Hepatotoxic drugs (such as Dapsone, Erythromycin, Fluconazole, Ketoconazole, Rifampin) have been taken for a long period of time (over 7 consecutive days) in the 6 months before screening;
10. Those who have taken any clinical trial drugs within 3 months;
11. Any drug that changes liver enzyme activity was taken within 28 days before taking the study drug;
12. Any prescription or over-the-counter drugs taken within 14 days before taking the study drug;
13. Ingested any vitamin products, health products or Chinese herbal medicine within 14 days before taking the study drug;
14. HCV antibody positive, HIV antibody positive, HBsAg positive, syphilis antibody positive;
15. Ingested grapefruit or products containing grapefruit, food or drink containing caffeine, xanthine or alcohol within 48 hours before taking the study drug; strenuous exercise, or other factors that affect the absorption, distribution, metabolism, and excretion of the study drug;
16. The subjects have a childbearing plan and are unwilling to take effective contraceptive measures 2 weeks before the study administration (only female subjects) and 3 months after the last administration of the drug; those who are fertile and whose serum hCG test is not negative before the study medication;
17. People with a history of fainting needles and blood, have difficulty in blood collection or cannot tolerate venipuncture blood collection;
18. Women during pregnancy and lactation;
19. Subjects with other factors not suitable to participate in this study as considered by the investigator.

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: experimental group; Single-dose oral administration of SHR2554 and multiple-dose oral administration of Rifampin Capsules	Drug: SHR2554 and Rifampin; Single-dose oral administration of SHR2554 and multiple-dose oral administration of Rifampin Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter: Cmax of SHR2554	Peak Plasma Concentration (Cmax) of SHR2554	from Day 1 to Day 13
Pharmacokinetics parameter: AUC of SHR2554	Area under the plasma concentration versus time curve (AUC) of SHR2554	from Day 1 to Day 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other pharmacokinetics parameter: Tmax of SHR2554	Time to maximum plasma concentration (Tmax) of SHR2554	from Day 1 to Day 13
Other pharmacokinetics parameter: T1/2 of SHR2554	Half-life of elimination (T1/2) of SHR2554	from Day 1 to Day 13
The incidence and severity of adverse events/serious adverse events	Based on NCI-CTC AE 5.0	from Day 1 to Day 13

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2020
• Primary Completion (Actual): August 30, 2020
• Study Completion (Actual): September 20, 2020

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: October 6, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: SHR2554-I-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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