Safety/Tolerability and Pharmacokinetics/Pharmacodynamics of YH12852 After Oral Administration in Healthy Male Subjects

Study Overview
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Brief Summary
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Study to evaluate the safety/tolerability and pharmacokinetics/pharmacodynamics(PK/PD)of YH12852 after oral administration in healthy subjects

Official Title
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A Randomized, Double-blind, Placebo/Active-controlled, Single/Multiple Dose Phase 1 Clinical Study to Investigate the Safety/Tolerability and PK/PD of YH12852 After Oral Administration in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: YH12852
* Drug: Prucalopride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy male/female aged 19 to 45 with body mass index(BMI) between 18 and 25kg/m2 Subject who has no congenital, chronic disease and disease symptoms in medical examination result Subject who is judged to be eligible by principal investigator or sub-investigator according to various reasons including their abnormal test results(clinical laboratory test, 12-lead ECG etc) Subjects who has signed a written informed consent voluntarily,prior to any procedure, using a form that is approved by the local Institutional Review Board after detail explanation of the purpose, contents, and characteristic of the drug Exclusion Criteria: Subject who has history or presence of clinically significant diseases in liver, kidney, gastrointestinal tract, nervous system, respiratory system, endocrine system, blood tumor, cardiovascular, urinary system, and mental disorder Subject who is hypersensitive to components contained in YH12852 or prucalopride or aspirin/antibiotics like drugs Medical history of gastrointestinal disease or acid restraining surgery, gastric/ esophagus surgery(excluding appendectomy, hernia surgery) Clinically significant abnormal values in diagnostic check within 28 days before the treatment(>1.25 fold of normal upper limit in the levels of AST or ALT, >1.5 fold of normal upper limit in the levels of Total bilirubin, < 80ml/min of Cockcroft-Gault used creatinine clearance Subject has over QTc interval of 550 ms or PR interval of 210 ms or QRS interval of 120 ms or QT interval of 500 ms on baseline 12-lead ECG, as determined by the Investigator Subject who had taken usual dose of any prescription drugs within 14 days before the treatment or who had used usual dose of OTC drugs within 7 days before the treatment Subject who participated in another clinical trail within 2 months before enrolling in this study subject who donated whole blood within 2 months or component blood within 1 month before the treatment Medically unacceptable contraception used during the clinical trial Subject who drank over 30g/day or were detected alcohol positive on test Subject who stopped smoking within 3 months before the treatment or weren't able to stop smoking during the hospitalization Subject who had a beverage containing caffeine during the hospitalization Subjects with clinically significant observations considered as unsuitable based on medical judgment by investigators

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YH12852<br><SAD cohort> Experimental: YH12852 1mg/single dose, qd Experimental: YH12852 3mg/single dose, qd Experimental: YH12852 10mg/single dose, qd <FSD cohort> Experimental: YH12852 0.5mg/single dose, qd Experimental: YH12852 1mg/single dose, qd Experimental: YH12852 2mg/single dose, qd Experimental: YH12852 3mg/single dose, qd <MAD cohort> Experimental: YH12852 0.5mg/repeat dose, qd Experimental: YH12852 1mg/repeat dose, qd Experimental: YH12852 2mg/repeat dose, qd Experimental: YH12852 3mg/repeat dose, qd Each dosing group(except MAD cohort 0.5mg which has single treatment arm taking YH12852 only) contains 12 subjects. 12 subjects are administered YH12852 or placebo/active comparators.(YH12852:placebo:active=8:2:2) | Drug: YH12852<br> <br> |
| Active Comparator: Prucalopride<br><each cohort> Prucalopride succinate 1.321mg | Drug: Prucalopride<br> <br> |
| Placebo Comparator: Placebo<br><each cohort> Matching Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the number of adverse events, seriousness of adverse event |  | D1 Post study visit | 
| significant changes in vital sign |  | D1 Post study visit | 
| significant changes in 12-lead electrocardiography |  | D1 Post study visit | 
| significant changes in laboratory test |  | D1 Post study visit | 
| significant physical exam |  | D1 Post study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax |  | 0 48 hrs(SAD,FSD cohorts), 0 24 hrs/D5,6 0hr/D7 0 48hrs(MAD cohort) | 
| AUC |  | 0 48 hrs(SAD,FSD cohorts), 0 24 hrs/D5,6 0hr/D7 0 48hrs(MAD cohort) | 
| Ae |  | 0 48 hrs(SAD cohort), 0 24 hrs/D7 0 48hrs(MAD cohort) | 
| BSFS | pharmacodynamics | D1 7(SAD, FSD cohorts), D1 14(MAD cohort) | 
| Frequency of defecation | pharmacodynamics | D1 7(SAD, FSD cohorts), D1 14(MAD cohort) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, tolerability, pharmacokinetics, pharmacodynamics