Study to Evaluate Pharmacokinetic Drug Interactions and Safety of Clarithromycin, Amoxicillin and Ilaprazole

Study Overview
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Brief Summary
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This study evaluate the pharmacokinetic drug interaction in Ilaprazole, Clarithromycin, Amoxicillin.

Detailed Description
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This study evaluate the pharmacokinetic drug interaction and safety in Ilaprazole, Clarithromycin, Amoxicillin.

Official Title
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A Randomized, Open-label, Parallel-design Study to Evaluate Pharmacokinetic Drug Interactions and Safety After Coadministration of Clarithromycin, Amoxicillin and Ilaprazole

Conditions
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Drug Interaction Potentiation

Intervention / Treatment
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* Drug: Ilaprazole 10mg
* Drug: Clarithromycin 500mg
* Drug: Amoxicillin 500 Mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male adults aged ≥19 years and <50 years at screening Body mass index ≥18.5 and <25 Body mass index (kg/m2) = body weight (kg)/[height (m)]2 Men who have sexual relationship with women of child bearing potential must give consent to using contraceptive measures (condoms, spermicide, and menstrual cycle control) and avoiding sperm donation during the study and up to 28 days following the last dose of IMP (these contraceptive measures are not required if the male subject or female partner is infertile). Those who voluntarily decided to participate in this study and gave written consent to comply with the requirements after receiving sufficient explanation and fully understanding this study. Exclusion Criteria: Hypersensitivity or history of clinically significant hypersensitivity to active ingredients or excipients (in particular, Yellow No. 4 (Tartrazine); Yellow No. 5 (Sunset Yellow FCF); macrolide antibiotics such as Clarithromycin and erythromycin; or Penicillins) History of QT prolongation or ventricular arrhythmia (including Torsadedes de pointes) Clinically significant, current or past disorder of hepatobiliary (severe hepatic impairment, etc.), renal (severe renal impairment, etc.), nervous, immune, respiratory, endocrine, blood•tumor, cardiovascular (heart failure, etc.), or psychiatric system History of gastrointestinal disorder (Crohn's disease, ulcer, etc.) or operation (excluding simple appendectomy or herniotomy) that may affect drug absorption Administration of other IMP from other study (including biological comparability test) within 3 months of the first dose of IMP. Whole blood donation within 60 days, or apheresis donation within 30 days before the first dose of IMP. Constant caffeine intake (> 5 cups of coffee/day, > 1250 cc of tea/day, > 1250 cc of cola/day), constant smoking (more than 10 cigarettes/day) or constant alcohol drinking (more than 210 g/week) or inability to refrain from alcohol consumption from 2 days before the first dose of IMP until the end of PK assessment. Consumption of grapefruit-containing food within 7 days before the first dose of IMP History of drug abuse within 1 year before screening, or positive response in urine drug misuse/abuse screening test Use of medicinal products that are expected to or may affect the metabolism of IMP; St. John's wort; or relevant preparations within 30 days of IMP administration Use of following medicinal products within given time period excluding local preparations, which do not have significant systemic absorption, and hormonal contraceptives Prescription drug within 14 days of the first dose of IMP OTC including health supplements and vitamins within 7 days of the first dose of IMP Medicinal products via depot injection or other implantations within 30 days of the first dose of IMP (excluding contraceptives) Drug metabolizing enzyme inducer or inhibitor such as barbiturate within 30 days before the first dose of IMP Stable vital sign measured in sitting position at screening: systolic blood pressure > 150 mmHg or < 90 mmHg, diastolic blood pressure > 100 mmHg or < 50 mmHg, pulse rate > 110 bpm or <40 bpm Following findings at screening Blood total bilirubin > 1.5 x upper limit of normal Blood AST (SGOT), ALT (SGPT) > 1.25 x upper limit of normal MDRD-estimated eGFR < 60 mL/min/1.73m2 eGFR (estimated glomerular filtration rate)(mL/min/1.73m2) = 175 x [serum creatinine (mg/dL)]-1.154 x [age (years)]-0.203 Positive serum test (hepatitis B, hepatitis C, HIV, syphilis) Those considered ineligible by the investigator due to other screening results or reasons.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ilaprazole 10mg<br>Period 1: Ilaprazole 10mg 1 tab.m one a day Period 2: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap. twice a day, 6 days Ilaprazole 10mg, one a day at the 5 day | Drug: Ilaprazole 10mg<br>* Period 1: Ilaprazole 10mg, one a day, one day Period 2: Ilaprazole 10mg, twice a day, 6 days<br>* Other names: Noltec(the brand name);|
| Active Comparator: Clarithromycin 500mg<br>Period 1: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day Period 2: Ilaprazole 10mg 1 tab., twice a day, 6 days Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day at the 5 day | Drug: Clarithromycin 500mg<br>* Period 1: Clarithromycin 500mg 1 tab., twice a day, one day Period 2: Clarithromycin 500mg 1 tab., one a day at 5 day<br>* Other names: Klaricid 500mg(the brand name);|
| Active Comparator: Amoxicillin 500mg<br>Period 1: Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day Period 2: Ilaprazole 10mg 1 tab., twice a day, 6 days Clarithromycin 500mg 1 tab. + Amoxicillin 500mg 2 cap., one a day at 5 day | Drug: Amoxicillin 500 Mg<br>* Period 1: Amoxicillin 500mg 2 cap., one a day, one day Period 2: Amoxicillin 500mg 2 cap., one a day at 5 day<br>* Other names: Amoxicillin Cap. 500mg Chongkundang(the brand name);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ilaprazole AUClast(Area Under the plasma concentration-time Curve at the last observed time point) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Ilaprazole Cmax(the maximum serum concentration) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin AUClast |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin Cmax |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ilaprazole AUCinf(Area Under the plasma concentration-time Curve from time zero to infinity) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Ilaprazole Tmax(the time to reach Cmax) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Ilaprazole t1/2(the elimination half-life) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Ilaprazole CL/F(the oral clearance) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Ilaprazole Vd/F(apparent volume of distribution after non-intravenous administration) |  | Predose(0h), after dose 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin AUCinf |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin Tmax |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin t1/2 |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin CL/F |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h | 
| Clarithromycin, Amoxicillin Vd/F |  | Predose(0h), after dose 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48h |