Sarpogrelate Drug Interaction

Study Overview
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Brief Summary
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This is a randomized, open-label, single & multiple-dose, three-sequence, three-period crossover study to investigate the effect of sarpogrelate hydrochloride on the disposition of metoprolol tartrate in healthy male volunteers

Detailed Description
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Eligibility for participation of this study will be determined from demographic information, medical history, physical examination, electrocardiogram (ECG) and clinical laboratory tests within 4 weeks before study drug administration. Subjects suitable for this study will be admitted to the Clinical Trial Center of Ajou University Medical Center on the day before dosing (Day -1). On Day 1, Subjects will be dosed study drug (metoprolol tartrate 100 mg once a day only, or metoprolol tartrate 100 mg once a day with sarpogrelate hydrochloride 100 mg three times a day, sarpogrelate hydrochloride 100 mg three times a day pretreatment for three days and metoprolol tartrate 100 mg once a day with sarpogrelate hydrochloride 100 mg three times a day). Pharmacokinetic samplings and blood pressure/pulse rate measurement will be done upto 12 hours after metoprolol tartrate 100 mg dosing. After one week of washout period (Day 8), Subjects will be dosed study drug by crossover manner, and pharmacokinetic samplings and blood pressure/pulse rate measurement will be done upto 12 hours after metoprolol tartrate 100 mg dosing. After one week of washout period (Day 15), Subjects will be dosed study drug by crossover manner, and pharmacokinetic samplings and blood pressure/pulse rate measurement will be done upto 12 hours after metoprolol tartrate 100 mg dosing.

Official Title
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A Randomized, Open-label, Three-sequence, Three-period Crossover Study to Investigate The Effect of Anplag on the Disposition of Betaloc in Healthy Male Volunteers

Conditions
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Hypertension, Peripheral Artery Disease

Intervention / Treatment
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* Drug: Sarpogrelate pretreatment
* Drug: Sarpogrelate
* Drug: Metoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 20 - 45 years With in 20% of ideal body weight, {Ideal body weight=[height(cm)-100]*0.9} Agreement with written informed consent Exclusion Criteria: Clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal disease or mental disorder (Past history or present) Inadequate result of laboratory test (especially, AST/ALT > 1.25 x UNL, Total bilirubin > 1.5 x UNL) Positive reaction in the HBs Ag, anti-HCV Ab, anti-HIV Ab, VDRL test Taking OTC(Over the counter)medicine including oriental medicine within 7 days Clinically significant allergic disease (Except for mild allergic rhinitis and dermatitis seems to be not need for medication) Subject with known for hypersensitivity reaction to Metoprolol or Sarpogrelate Previous whole blood donation within 60 days or component blood donation within 30 days Previous participation of other trial within 90 days Continued taking caffeine (caffeine > 5 cup/day), drinking (alcohol > 30 g/day) and severe heavy smoker (cigarette > 1/2 pack per day) An impossible one who participates in clinical trial by investigator's decision including for reason of laboratory test result

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sarpogrelate pretreatment and Metoprolol<br>Sarpogrelate hydrochloride 100 mg pretreatment three times a day for three days and Metoprolol Tartrate 100 mg once a day with Sarpogrelate hydrochloride 100 mg three times a day | Drug: Sarpogrelate pretreatment<br>* Sarpogrelate hydrochloride 100 mg pretreatment three times a day for three days<br>Drug: Sarpogrelate<br>* Sarpogrelate hydrochloride 100 mg three times a day<br>Drug: Metoprolol<br>* Metoprolol Tartrate 100 mg once a day<br>|
| Active Comparator: Sarpogrelate and Metoprolol<br>Metoprolol Tartrate 100 mg once a day with Sarpogrelate hydrochloride 100 mg three times a day | Drug: Sarpogrelate<br>* Sarpogrelate hydrochloride 100 mg three times a day<br>Drug: Metoprolol<br>* Metoprolol Tartrate 100 mg once a day<br>|
| Active Comparator: Metoprolol only<br>Metoprolol Tartrate 100 mg once a day | Drug: Metoprolol<br>* Metoprolol Tartrate 100 mg once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of Metoprolol and metabolites | Cmax (maximal plasma concentration) and AUC (area under the time-concentration curve) will be calculated from pharmacokinetic samplings | upto 12 hours after Metoprolol Tartrate 100 mg dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure and pulse rate changes | Blood pressure and pulse rate measurement with Dash 5000 patient monitoring system (GE Healthcare, USA) at 0 (before Metoprolol Tartrate 100 mg dosing), 1, 2, 3, 4, 5, 6, 8, 10, 12 hours after Metoprolol Tartrate 100 mg dosing | Upto 12 hours after Metoprolol Tartrate 100 mg dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-drug interaction, Pharmacokinetics, Pharmacodynamics