Dose-escalation, Repeated and Single Oral Dosing Study

Study Overview
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Brief Summary
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Randomized, Double-blind, Placebo-controlled, Dose-escalation, Repeated and Single Oral Dosing Phase I Study to Assess the Pharmacokinetics, Pharmacodynamics and Safety of APD791 (Temanogrel) Co-administered with Aspirin and Clopidogrel.

Detailed Description
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To investigate pharmacokinetic and pharmacodynamic characteristics of Temanogrel when orally co-administered with Aspirin and/or Clopidogrel in healthy subject. a person determined to be suitable for the purpose of this clinical trial by investigator with consideration for the age and the health status of a volunteer is selected Assess the safety of Temanogrel when orally co-administered with Aspirin and/or Clopidogrel in healthy subjects.

Official Title
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Randomized, Double-blind, Placebo-controlled, Dose-escalation, Repeated and Single Oral Dosing Phase I Study to Assess the Pharmacokinetics, Pharmacodynamics and Safety of Temanogrel Co-administered With Aspirin and Clopidogrel

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: APD791
* Drug: Clopidogrel
* Drug: Aspirin
* Drug: Placebo for APD791


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a healthy adult between 20 and 45 years old at the time of visit for screening a person who is able to give written consent a person between 50 and 85 kg at the time of visit for screening a woman who is negative on a serum hCG test at the time of visit and the day before a trial, and who is not nursing, a woman who agrees on double contraception, medically approved, from the time of visit for screening to 90 days after the last administration of a clinical trial drug, or who had a contraceptive operation no later than 120 days before visit for screening, or who is menopausal, a man who had a contraceptive operation no later than 120 days before visit for screening, or who agrees on double contraception, medically approved, from the time of visit for screening to 90 days after the last administration of a clinical trial drug, and also agree not to donate sperm a person more than hemoglobin 12 g/dL at the time of screening (a woman more than hemoglobin 11 g/dL) a person whose vital signs were in the normal range at the time of visit for screening, or who is medically determined not to be clinically significant by an investigator Exclusion Criteria: a person with the medical history of gastric ulcer, duodenal ulcer or esophageal ulcer within 90 days from the time of visit for screening a person with the medical history of gastrointestinal diseases(e.g. Crohn's disease, ulcerative colitis, etc.) or surgery(excluding uncomplicated appendectomy or herniotomy) affecting the absorption of a clinical trial drug a person with the medical history of blood coagulation disorder or hemorrhagic diseases, or with clinically significant abnormal findings decided by a investigator on blood coagulation test at the time of screening a woman with the medical history of dysfunctional uterine bleeding within a year from the time of visit for screening a person with the medical history of epilepsy or convulsion a person with the medical history of internal organ transplant a person expected to be hard to complete a clinical trial because of surgery or medical procedures planned within a clinical trial period a person with the medical history of clinically significant new diseases within 30 days from the time of visit for screening according to investigator's decision a person with hypersensitivity reaction to a drug or gelatin, or the medical history of clinically significant hypersensitivity reaction a person with the history of drug abuse, or with a positive reaction to a drug possible to be abused on urine drug screening a person with the medical history of alcohol abuse within two years from the time of visit for screening a person who is a smoker, or with a positive reaction on a urine nicotine test conducted at the time of visit for screening a person who donated whole blood within 60 days or constituents of blood within 30 days, or received a blood transfusion within 30 days from the time of visit for screening a person taking other clinical trial drugs within 90 days from the time of visit for screening a person taking a prescription drug within 30 days, or a contraindicated drug or oriental medicine within 14 days from the time of visit for screening a person with a positive reaction to a serum test(hepatitis B test, hepatitis C test, HIV test, syphilis test) a person with hepatic enzymes(AST, ALT) more than 2.5 times of the reference upper limit(UNL) or total bilirubin more than 1.5 times of the reference upper limit(UNL) or creatinine more than 1.25 times of the reference upper limit(UNL) a person expected to be hard to complete a clinical trial due to physical or mental status according to investigator's medical decision at the time of visit for screening

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APD791 10mg single dose<br>APD791 10mg single dose | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;|
| Experimental: APD791 20mg single dose<br>APD791 20mg single dose | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;|
| Experimental: APD791 40mg single dose<br>APD791 40mg single dose | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;|
| Experimental: APD791 10mg<br>APD791 10mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 20mg<br>APD791 20mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 40mg<br>APD791 40mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 80mg<br>APD791 80mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 160mg<br>APD791 160mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 240mg<br>APD791 240mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 320mg<br>APD791 320mg single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Placebo Comparator: APD791 Placebo<br>APD791 placebo for single dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;Drug: Placebo for APD791<br>* Placebo for APD791<br>* Other names: Placebo for Temanogrel;|
| Experimental: APD791 2mg MD<br>APD791 2mg multiple dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 5mg MD<br>APD791 5mg multiple dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 10mg MD<br>APD791 10mg multiple dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Experimental: APD791 20mg MD<br>APD791 placebo for multiple dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;|
| Placebo Comparator: APD791 placebo MD<br>APD791 placebo for multiple dose + Aspirin + Clopidogrel | Drug: APD791<br>* Temanogrel<br>* Other names: Temanogrel;Drug: Clopidogrel<br>* Clopidogrel<br>* Other names: Plavix;Drug: Aspirin<br>* Aspirin<br>* Other names: Aspirin Protect;Drug: Placebo for APD791<br>* Placebo for APD791<br>* Other names: Placebo for Temanogrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics-Cmax |  | Day1, Day2, Day3, Day4, Day 7 | 
| Pharmacokinetics-Tmax |  | Day1, Day2, Day3, Day4, Day 7 | 
| Pharmacodynamics-% inhibition of serotonin-stimulated platelet aggregation |  | Day1, Day2, Day4, Day7, Day 8 | 
| Pharmacodynamics-change of serotonin-stimulated platelet aggregation |  | Day1, Day4, Day7 | 
| Pharmacodynamics-% inhibition of TRAP-induced platelet aggregation |  | Day1, Day4, Day7 of every dose for mutiple dose group and first day for single dose group. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event monitoring |  | up to post-study visit(8day±2) | 
| physical examination |  | up to post-study visit(8day±2) | 
| vital signs |  | up to post-study visit(8day±2) | 
| ECG |  | up to post-study visit(8day±2) | 
| laboratory test |  | up to post-study visit(8day±2) |