Bioequivalence Study Between DA-5209 Tab and Lixiana Tab

Study Overview
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Brief Summary
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An Open-Label, Randomized, 6-sequence, 3-period, Fasting Condition, Single-dose, Per Oral, Cross-over Study to Evaluate the Bioequivalence between DA-5209 60mg Tab and Lixiana 60mg Tab in Healthy Volunteers

Detailed Description
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Study design: An open-Label, randomized, 6-sequence, 3-period, fasting condition, single-dose, per oral, cross-over study Administration method: The subject should maintain a minimum of 10 hours of empty stomach before administration, and give an oral dose of 1 tablets (DA-5209 60mg) without water or (DA-5209 60mg or Lixiana 60mg) with 150 mL of water at around 8 a.m. on the day of the test. The subject should not chew or break the drug, but should swallow in whole with water. The difference in administration time between the test subjects is about one minute apart, considering the blood collection time. Wash out period: at least 7 days Blood collection time: Before the administration, 5, 10, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hr after the administration (total 15 times) Analysis: Measurement of the concentration of an unchangeable substance of Edoxaban in plasma

Official Title
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A Open-Label, Randomized, 6-sequence, 3-period, Fasting Condition, Singledose, Per Oral, Cross-over Study to Evaluate the Bioequivalence Between DA-5209 60mg Tab and Lixiana 60mg Tab in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: DA-5209 60mg Tab
* Drug: DA-5209 60mg Tab
* Drug: Lixiana 60mg Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A person who aged 19 or older at the time of screening BMI of 18 to 30 (BMI calculation: kg/m2) ◦Males or Females weighing 60kg or more No congenital or chronic diseases or pathological symptoms A person who is judged to be suitable for the study by the investigator based on the clinical laboratory examination A person who has fully understood the contents of the consent form for the study and signed the consent form voluntarily and recorded the date of signature A person who agreed to use contraception from the first administration of IP to a week after the last administration of IP Exclusion Criteria: A person who has taken a drug that significantly induces (e.g., barbital) or inhibits the drug metabolic enzyme within 30 days prior to the first administration of IP A person who has participated in other clinical trials within six months prior to the first administration of the IP A person who has had whole blood transfusion within 2 months or the apheresis within 2 weeks before the first administration of IP A person who has medical history of gastric resection that can affect the drug absorption A person with a history of regular alcohol intake within a month prior to the first administration of the IP: Male: More than 21 cups/week Female: More than 14 cups/week (1 cup: 50 ml of soju, 250 ml of beer, 30ml of spirits) A person who is hypersensitive to any of the IP components, with clinically significant bleeding, with end-stage renal disease and have kidney dialysis, with hepatic disease related to blood coagulation disorder and clinically significant risk of bleeding, with severe liver impairment, with an increased risk of bleeding, use combination therapy with other anticoagulants, Severe hypertension factor, have undergone artificial heart valve replacement A person who has medical history of mental disease A person who is judged not to be suitable for the study by the investigator Lactating or possibly pregnant women

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover Assignment single-dose, 6-sequence, 3-period Bioequivalence Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T1T2R<br>Period I: T1, DA-5209 60mg without water Period II: T2, DA-5209 60mg with 150mL water Period III: R, Lixiana 60mg with 150mL water | Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab with 150mL water<br>Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab without water<br>Drug: Lixiana 60mg Tab<br>* single oral administration of 1 tablet of Lixiana 60mg Tab with 150mL water<br>|
| Experimental: T1RT2<br>Period I: T1, DA-5209 60mg without water Period II: R, Lixiana 60mg with 150mL water Period III: T2, DA-5209 60mg with 150mL water | Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab with 150mL water<br>Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab without water<br>Drug: Lixiana 60mg Tab<br>* single oral administration of 1 tablet of Lixiana 60mg Tab with 150mL water<br>|
| Experimental: RT1T2<br>Period I: R, Lixiana 60mg with 150mL water Period II: T1, DA-5209 60mg without water Period III: T2, DA-5209 60mg with 150mL water | Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab with 150mL water<br>Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab without water<br>Drug: Lixiana 60mg Tab<br>* single oral administration of 1 tablet of Lixiana 60mg Tab with 150mL water<br>|
| Experimental: RT2T1<br>Period I: R, Lixiana 60mg with 150mL water Period II: T2, DA-5209 60mg with 150mL water Period III: T1, DA-5209 60mg without water | Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab with 150mL water<br>Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab without water<br>Drug: Lixiana 60mg Tab<br>* single oral administration of 1 tablet of Lixiana 60mg Tab with 150mL water<br>|
| Experimental: T2RT1<br>Period I: T2, DA-5209 60mg with 150mL water Period II: R, Lixiana 60mg with 150mL water Period III: T1, DA-5209 60mg without water | Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab with 150mL water<br>Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab without water<br>Drug: Lixiana 60mg Tab<br>* single oral administration of 1 tablet of Lixiana 60mg Tab with 150mL water<br>|
| Experimental: T2T1R<br>Period I: T2, DA-5209 60mg with 150mL water Period II: T1, DA-5209 60mg without water Period III: R, Lixiana 60mg with 150mL water | Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab with 150mL water<br>Drug: DA-5209 60mg Tab<br>* single oral administration of 1 tablet of DA-5209 60mg Tab without water<br>Drug: Lixiana 60mg Tab<br>* single oral administration of 1 tablet of Lixiana 60mg Tab with 150mL water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the plasma Concetration versus time curve(AUCt) of Edoxaban | Area Under the plasma Concetration versus time curve(AUCt) of Edoxaban | Before administration   48hours | 
| Peak Plasma Concentration(Cmax) of Edoxaban | Peak Plasma Concentration(Cmax) of Edoxaban | Before administration   48hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absorption rate constant(Ka) of Edoxaban | Absorption rate constant(Ka) of Edoxaban | Before administration   48hours | 
| % of concentration compared to Maximum observed plasma concentration(Cmax) of Edoxaban | % of concentration compared to Maximum observed plasma concentration(Cmax) of Edoxaban | Before administration   48hours | 
| Area under the plasma drug concentration-time curve from time 0 to infinity(AUC∞) of Edoxban | Area under the plasma drug concentration-time curve from time 0 to infinity(AUC∞) of Edoxban | Before administration   48hours | 
| Area under the plasma drug concentration-time curve/Area under the plasma drug concentration-time curve from time 0 to infinity(AUCt/AUC∞) of Edoxaban | Area under the plasma drug concentration-time curve/Area under the plasma drug concentration-time curve from time 0 to infinity(AUCt/AUC∞) of Edoxaban | Before administration   48hours | 
| Time of peak concentration(Tmax) of Edoxaban | Time of peak concentration(Tmax) of Edoxaban | Before administration   48hours | 
| Terminal phase of Half-life(t1/2) of Edoxaban | Terminal phase of Half-life(t1/2) of Edoxaban | Before administration   48hours |