A Phase I Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety in Healthy Subjects with Multiple Administration of Tiprogrel
Overview
- Phase
- Phase 1
- Intervention
- Tiprogrel
- Conditions
- Acute Coronary Syndrome
- Sponsor
- Tianjin Institute of Pharmaceutical Research Co., Ltd
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- PK parameters： Cmax
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study is designed to evaluate the pharmacokinetics, pharmacodynamics and safety in healthy subjects with multiple administration of Tiprogrel.
Detailed Description
Tiprogrel is a novel oral P2Y12 receptor antagonist.This study is to evaluate the pharmacokinetics, pharmacodynamics and safety in healthy subjects with multiple administration of Tiprogrel, and compare pharmacokinetics /pharmacodynamic of Tiprogrel,Clopidogrel and Ticagrelor.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female Healthy Subjects
- •Subject has the ability and willingness to comply with study procedures and follow-up examination.
- •3：18 to 50 years of age (including the threshold) 4: Body mass index (BMI) ≥ 19.0 to ≤ 28.0 kg/m2; total body weight of male subject ≥ 50 kg at Screening; total body weight of female subject ≥ 45 kg at Screening; 5：Medically healthy based on their medical history, and physical examination, clinical laboratory test results, ECGs, and vital sign measurements as determined by the Investigator at Screening; 6: Female subjects are not pregnant or breastfeeding, and the fertile female and male subjects must agree to follow instructions for method(s) of contraception.
Exclusion Criteria
- •History or presence of metabolic, allergy, dermatology, liver, kidney, hematology, cardiovascular, gastrointestinal, nervous, respiratory, endocrine or psychiatric diseases.
- •History or presence of obviously active bleeding, or coagulation or bleeding disorders, or any skin petechiae, or thrombus, or spontaneous bleeding.
- •Subject with history of allergy to a variety of drugs, or has a known or suspected hypersensitivity to tiprogrel or other anti-platelet drugs
- •Subjects who had a history of major surgery within 3 months before the trial or planned to undergo surgery during the study period.
- •Subjects who have lost or donated ≥ 400 mL blood or received blood transfusion or used blood products within three months, or subjects with clinically significant anemia based on the judgment of the Investigator
- •Subjects with systolic blood pressure of \> 140 mmHg or \< 90 mmHg, diastolic blood pressure of \> 90 mmHg or \< 60 mmHg
- •Subjects with 12-lead ECG examination: QTcF \> 450 msec
- •Platelet count (PLT) value, beyond the laboratory's reference range
- •Activated partial thromboplastin time (APTT) and Prothrombin Time (PT), beyond the laboratory's reference range
- •ALT, AST, γ-GGT, ALP and TBIL value \>1.5 times the upper limit of normal value
Arms & Interventions
Tiprogrel-Clopidogrel-Ticagrelor
Period 1: Dose 1 Tiprogrel; Period 2: Dose 2 Tiprogrel ; Period 3: Clopidogrel; Period 4: Ticagrelor
Intervention: Tiprogrel
Tiprogrel-Clopidogrel-Ticagrelor
Period 1: Dose 1 Tiprogrel; Period 2: Dose 2 Tiprogrel ; Period 3: Clopidogrel; Period 4: Ticagrelor
Intervention: Clopidogrel
Tiprogrel-Clopidogrel-Ticagrelor
Period 1: Dose 1 Tiprogrel; Period 2: Dose 2 Tiprogrel ; Period 3: Clopidogrel; Period 4: Ticagrelor
Intervention: Ticagrelor
Outcomes
Primary Outcomes
PK parameters： Cmax
Time Frame: Day 1 to Day 9 in each period
Maximum Concentration of Clopidogrel 's active metabolite
PK parameters： AUC
Time Frame: Day 1 to Day 9 in each period
Area under the plasma concentration curve of Clopidogrel 's active metabolite
PK parameters： Tmax
Time Frame: Day 1 to Day 9 in each period
Time to maximum concentration of Clopidogrel 's active metabolite
PK parameters： T1/2
Time Frame: Day 1 to Day 9 in each period
Half life of Clopidogrel 's active metabolite
PD parameters: Adenosine Diphosphate(ADP)-induced P2Y12 Receptor-mediated platelet aggregation of Tiprogrel
Time Frame: Day 1 to Day 14 in each period
ADP-induced platelet reaction unit represents the rate and extent of ADP-stimulated platelet aggregation
PD parameters: Adenosine Diphosphate(ADP)-induced P2Y12 Receptor-mediated platelet aggregation of Clopidogrel
Time Frame: Day 1 to Day 14 in each period
ADP-induced platelet reaction unit represents the rate and extent of ADP-stimulated platelet aggregation
PD parameters: Adenosine Diphosphate(ADP)-induced P2Y12 Receptor-mediated platelet aggregation of Ticagrelor
Time Frame: Day 1 to Day 14 in each period
ADP-induced platelet reaction unit represents the rate and extent of ADP-stimulated platelet aggregation
Safety parameters: Number of Participants With Treatment-Related Adverse Events
Time Frame: Day 1 to Day 14 in each period