The DDI Study Had Been Designed to Investigate the Effect of SHR3680 on the Pharmacokinetics of Midazolam, S-Warfarin and Omeprazole

A Single-center, Open-label, Fixed-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of SHR3680 With Midazolam （CYP3A4 Substrates), S-Warfarin (CYP2C9 Substrates) and Omeprazole (CYP2C19 Substrates) in Prostate Cancer Patients

The DDI study had been designed to investigate the effect of SHR3680 on the pharmacokinetics of Midazolam, S-Warfarin and Omeprazole

Study Overview

• Status: Completed
• Conditions: Prostate Cancer Patients
• Intervention / Treatment: Drug: Midazolam, Warfarin, Omeprazole, VitaminK1 and SHR3680

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

Contacts and Locations

• Study Contact: Name: shijuan kuang; Phone Number: +8613601827797; Email: kuangshijuan@hrglobe.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 18 ≤ age ≤75, male;
• ECOG score of physical condition is 0 ~ 1;
• The expected survival time is at least 3 months;
• Prostatic adenocarcinoma confirmed by histological or cytological examination, with no indication of neuroendocrine or small-cell characteristics;

• The functional level of organs must meet the following requirements (no blood transfusion or hematopoietic growth factor treatment was received within 2 weeks before routine blood screening) :

  • ANC ≧ 1.5 x 109 / L;
  • PLT ≧ 80 x 109 / L;
  • Hb ≧ 90 g/L;
  • TBIL ≦1.5 x ULN;
  • ALT and AST≦2.5×ULN;
  • BUN and Cr ≦1.5 x ULN;
  • GFR ≧ 60 ml/min / 1.73 m2.
• According to the researcher's judgment, it can comply with the experimental scheme;
• Volunteer to participate in this clinical trial, understand the study procedures and have signed informed consent.

Exclusion Criteria:

• 1. Any previous anti-tumor therapy (including radiotherapy, chemotherapy, surgery, molecular targeted therapy, immunotherapy, etc.), except ADT therapy, shall be completed until the washout period of the first drug administration in this study is <4 weeks;
• Plan to receive any other anti-tumor therapy during the study;
• As subjects, to participate in other drug clinical trials, the last trial drug administration is less than 4 weeks from the first administration of the drug in this study;
• The presence of intracerebral tumor lesions according to imaging diagnosis;
• Have a history of epilepsy, or have diseases that can induce epileptic seizures within 12 months before the first administration of the drug in this study (including a history of transient ischemic attack, cerebral stroke (except cerebral ischemia lesions found by simple imaging examination), and need to be hospitalized with cerebral trauma and consciousness disorder);
• Active heart disease, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and drug-requiring ventricular arrhythmias, within 6 months prior to the first administration of the drug in this study;
• Inability to swallow, chronic diarrhea and ileus, history of gastrointestinal surgery, or other factors affecting drug use and absorption as determined by the investigator;
• Patients with active HBV or HCV infection (HBV copy count ≥ 104 copies /mL, HCV copy count ≥ 103 copies /mL) and active syphilis;
• A history of immunodeficiency (including HIV positive, other acquired or congenital immunodeficiency diseases) or a history of organ transplantation;
• Patients who were unwilling to use effective contraceptive methods during the whole study treatment period and within 3 months after the last administration;
• Allergic constitution, including a history of severe drug allergy or drug allergy;
• Screening for excessive smoking in the first 6 months (≥5 cigarettes/day) or smoking within 48 hours before the first dose, or not interrupting smokers during the main study trial, and screening for drug use in the first 3 months with a history of drug abuse or positive drug abuse screening;
• has a history of alcoholism or within 6 months prior to screening often drinkers, namely the essence of drinking more than 14 units of alcohol a week (1 = 360 mL of alcohol content of 5% beer or 45 mL of 40% alcohol liquor or 150 mL wine alcohol content of 12%) or within 48 h before taking the medicine for the first time drinking, or D - 1 in the alcohol breath test positive, or the body can't stop alcohol intake during the study period;
• Use of any vitamin product, health product or herb 14 days prior to the first administration;
• Ingestion of grapefruit or fruit juice products such as grapefruit, foods or beverages containing caffeine, xanthine or alcohol within 48 hours before taking the study drug;Strenuous exercise, or other factors affecting drug absorption, distribution, metabolism, and excretion;
• Within 2 weeks before the first drug uptake, uptake CYP3A4, CYP2C9 and CYP2C19 inhibitors were used, or drugs affecting gastric acid secretion. (Annex I);
• abnormal coagulation function at screening stage (INR >1.5 or prothrombin time (PT) > ULN+4 seconds or APTT> 1.5uln), bleeding tendency or thrombolytic therapy;
• Patients treated with anticoagulants or vitamin K1 antagonists such as warfarin, heparin, or similar drugs;
• Note: Under the condition that the international standard ratio of prothrombin time (INR) ≤1.5, low-dose heparin (66,000-12,000U daily for adults) or low-dose aspirin (100mg daily) is allowed for preventive purposes;
• Midazolam contraindications (benzodiazepine allergy, myasthenia gravis, schizophrenia, severe depression);
• Contraindications to Warfarin (liver and kidney function impairment, severe hypertension, coagulation dysfunction with bleeding tendency, active ulcer, trauma, threatened abortion, recent surgery);
• Concomitant diseases (such as poorly controlled hypertension, severe diabetes, thyroid disease, psychosis, etc.) or any other conditions that, in the investigator's judgment, would seriously endanger the patient's safety or affect the patient's completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHR3680+ Midazolam, Warfarin, Omeprazole, VitaminK1; administrate Midazolam, Warfarin, Omeprazole, VitaminK1 on Day1 and Day22, SHR3680 on day 6-27.	Drug: Midazolam, Warfarin, Omeprazole, VitaminK1 and SHR3680; Experimental: Midazolam, Warfarin, Omeprazole, VitaminK1 and SHR3680; Midazolam, Warfarin, Omeprazole and VitaminK1 QD on Day 1 and Day 22, SHR3680 240 mg once daily (QD) from Study Day 6 - 27

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameters of Midazolam, S-Warfarin and Omeprazole	Peak Plasma Concentration (Cmax)	Day1 and Day22
Pharmacokinetics parameters of Midazolam, S-Warfarin and Omeprazole	Area under the plasma concentration versus time curve (AUC)	Day1 and Day22

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2020
• Primary Completion (ACTUAL): January 26, 2022
• Study Completion (ACTUAL): January 26, 2022

Study Registration Dates

• First Submitted: November 22, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (ACTUAL): December 19, 2020

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Fibrin Modulating Agents; Gastrointestinal Agents; Micronutrients; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Vitamins; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Midazolam; Vitamin K; Warfarin; Omeprazole; Vitamin K 1
• Other Study ID Numbers: SHR3680-I-DDI-01

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