Dose-escalation, Repeated and Single Oral Dosing Study

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Clopidogrel; Drug: APD791; Drug: Aspirin; Drug: Placebo for APD791

Detailed Description

1. 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
2. Assess the safety of Temanogrel when orally co-administered with Aspirin and/or Clopidogrel in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. a healthy adult between 20 and 45 years old at the time of visit for screening
2. a person who is able to give written consent
3. a person between 50 and 85 kg at the time of visit for screening
4. 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
5. a person more than hemoglobin 12 g/dL at the time of screening (a woman more than hemoglobin 11 g/dL)
6. 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:

1. a person with the medical history of gastric ulcer, duodenal ulcer or esophageal ulcer within 90 days from the time of visit for screening
2. 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
3. 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
4. a woman with the medical history of dysfunctional uterine bleeding within a year from the time of visit for screening
5. a person with the medical history of epilepsy or convulsion
6. a person with the medical history of internal organ transplant
7. a person expected to be hard to complete a clinical trial because of surgery or medical procedures planned within a clinical trial period
8. 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
9. a person with hypersensitivity reaction to a drug or gelatin, or the medical history of clinically significant hypersensitivity reaction
10. a person with the history of drug abuse, or with a positive reaction to a drug possible to be abused on urine drug screening
11. a person with the medical history of alcohol abuse within two years from the time of visit for screening
12. a person who is a smoker, or with a positive reaction on a urine nicotine test conducted at the time of visit for screening
13. 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
14. a person taking other clinical trial drugs within 90 days from the time of visit for screening
15. 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
16. a person with a positive reaction to a serum test(hepatitis B test, hepatitis C test, HIV test, syphilis test)
17. 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)
18. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

16

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: IlDong Pharmaceutical Co Ltd
• Collaborators: Asan Medical Center
• Investigators: Principal Investigator: Gyunseop Bae, M.D., Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: January 27, 2015
• First Submitted That Met QC Criteria: April 16, 2015
• First Posted (Estimate): April 17, 2015

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 11, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Serotonin Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Aspirin; Clopidogrel; APD791
• Other Study ID Numbers: ID-TMG-102