A Drug Interaction Study Assess the Effects of ZSP1273 Tablets on the Pharmacokinetics of Warfarin and Midazolam

Study Overview
=================
Brief Summary
-----------------
This study is a single-center, open label phase I clinical study to characterize the DDIs potential of ZSP1273 With Warfarin and Midazolam in Chinese healthy participants. This study also aims to evaluate the safety and tolerability of ZSP1273 in the presence of Warfarin and Midazolam.

Official Title
-----------------
A Phase 1, Open-Label, Two-Period，Drug Interaction Study Assess the Effects of ZSP1273 Tablets on the Pharmacokinetics of Warfarin and Midazolam

Conditions
-----------------
Drug Drug Interaction, Warfarin, Midazolam

Intervention / Treatment
-----------------
* Drug: ZSP1273


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult, male and female participants, 18 to 55 years of age, inclusive, at first Check-In Visit; Body mass index (BMI) ≥19 to ≤26kg/m2 and total body weight >50 kg(male) or >45kg(female) at Screening (calculated as a function of measured height and weight according to the formula, BMI = kg / m2 where m2 is height in meters squared); Ability to understand and willingness to sign a written informed consent form; Normal physical examination, vital signs, 12-lead ECG, Chest X-ray images (anteroposterior) and clinical laboratory values, or any abnormality that is non-clinically significant. Exclusion Criteria: Participants with a history of hypersensitivity to study drug(ZSP1273,warfarin, midazolam) or any component of study medication; Participants with a history of and/or signs and symptoms of current abnormal hemostasis or blood dyscrasia or abnormal prothrombin time (PT), international normalized ratio (INR), or activated partial thromboplastin time at screening; Smoking more than 5 cigarettes per day within 3 months prior to screening，or who cannot stop using any tobacco products during the study period; Participants who donated blood/bleeding profusely (> 400 mL) 3 months prior to randomization; Those with clinically significant ECG abnormalities, or QTcF > 450ms in men and QTcF > 470ms in women; Participants who test positive at screening for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody or Syphilis spirochete-specific antibodies (TPPA); Participants who test positive at Screening and/or admission (Day -1) for alcohol abuse. Females who are pregnant, lactating, or likely to become pregnant during the study. History of dysphagia or any gastrointestinal disorder that affect absorption

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The DDI of ZSP1273 ,Warfarin and Midazolam<br>Warfarin and midazolam will be co-administered alone and in combination with ZSP1273. | Drug: ZSP1273<br>* Drug Warfarin oral Drug midazolam oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S-warfarin Maximum Plasma Concentration [Cmax] | To assess the effect of steady-state ZSP1273 on the pharmacokinetic (PK) of a single dose of S-warfarin | Day1 to Day28 | 
| Midazolam Maximum Plasma Concentration [Cmax] | To assess the effect of steady-state ZSP1273 on the pharmacokinetic (PK) of a single dose of midazolam and its active metabolite alpha-hydroxymidazolam | Day1 to Day28 | 
| S-warfarin Area under the curve[AUC0-inf] | To assess the effect of steady-state ZSP1273 on the pharmacokinetic (PK) of a single dose of S-warfarin | Day1 to Day28 | 
| Midazolam Area under the curve[AUC0-inf] | To assess the effect of steady-state ZSP1273 on the pharmacokinetic (PK) of a single dose of midazolam and its active metabolite alpha-hydroxymidazolam | Day1 to Day28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and serious adverse events | To assess the safety and tolerability of ZSP1273 following single and multiple-dose administration with and without midazolamin+S-warfarin in healthy participates | Day1 to Day28 |