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

Sponsor

Yuhan Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT01870674

Collaborator

(none)

127

Enrollment

Location

Arms

Duration (Months)

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: YH12852 Drug: Prucalopride Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

127 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

Apr 1, 2015

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: YH12852 <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
Active Comparator: Prucalopride <each cohort> Prucalopride succinate 1.321mg	Drug: Prucalopride
Placebo Comparator: Placebo <each cohort> Matching Placebo	Drug: Placebo

Arm

Intervention/Treatment

Experimental: YH12852

<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

Active Comparator: Prucalopride

<each cohort> Prucalopride succinate 1.321mg

Drug: Prucalopride

Placebo Comparator: Placebo

<each cohort> Matching Placebo

Drug: Placebo

Outcome Measures

Primary Outcome Measures

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

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 [D1~7(SAD, FSD cohorts), D1~14(MAD cohort)]
pharmacodynamics
Frequency of defecation [D1~7(SAD, FSD cohorts), D1~14(MAD cohort)]
pharmacodynamics

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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