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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Prucalopride; Drug: YH12852

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • Inje Busan Paik hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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, qdEach 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Yuhan Corporation

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 20, 2013
• First Submitted That Met QC Criteria: June 3, 2013
• First Posted (Estimate): June 6, 2013

Study Record Updates

• Last Update Posted (Estimate): May 8, 2015
• Last Update Submitted That Met QC Criteria: May 7, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; pharmacodynamics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride; YH12852
• Other Study ID Numbers: YH12852-101