Fimasartan (BR-A-657) Single Oral Dose in Healthy Subjects

BR-A-657, A Phase 1, Double-blind, Placebo-controlled, Ascending Single Oral Dose Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study in Healthy Male Subjects Incorporating a Comparison of Fed/Fasted Pharmacokinetics

The objective of this study is to determine the safety and tolerability and to determine the Pharmacokinetic and Pharmacodynamic (PK/PD) of ascending single oral dose of BR-A-657 in healthy male subjects.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: BR-A-657

Detailed Description

BR-A-657 20, 50, 120, 240, 360, 480mg or placebo were administered once to healthy male subjects.

Pharmacokinetic and Pharmacodynamic(PK/PD) parameters were monitored at pre-specified times from each subjects.

PK parameters: Area Under the Curve(AUC), Cmax, half-life, etc. PD parameters: Aldosterone, Plasma renin activity, Angiotensin I, Angiotensin II Adverse events are reported.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male of 18-55 years old
• Body Mass Index(BMI) 19-29kg/m2
• subjects in good health
• subjects with written informed consent

Exclusion Criteria:

• subjects with multiple drug allergy or allergy to Angiotensin Receptor Blocker(ARB)
• subjects with medication that affect drug absorption or elimination within 30days.
• subjects with orthostatic hypotension of >20mmHg decrease of Systolic Blood Pressure(SBP)
• subjects with history of neurologic, liver, renal, gastrointestinal, cardiovascular, psychological or other major disorder

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm A; BR-A-657 20mg or placebo	Drug: BR-A-657; 20, 60, 120, 240, 360, 480mg or placebo tablet; Other Names: Fimasartan; 20, 60, 120, 240, 360, 480mg
Other: Arm B; BR-A-657 60mg or placebo	Drug: BR-A-657; 20, 60, 120, 240, 360, 480mg or placebo tablet; Other Names: Fimasartan; 20, 60, 120, 240, 360, 480mg
Other: Arm C; BR-A-657 120mg or placebo	Drug: BR-A-657; 20, 60, 120, 240, 360, 480mg or placebo tablet; Other Names: Fimasartan; 20, 60, 120, 240, 360, 480mg
Other: Arm D; BR-A-657 240mg or placebo	Drug: BR-A-657; 20, 60, 120, 240, 360, 480mg or placebo tablet; Other Names: Fimasartan; 20, 60, 120, 240, 360, 480mg
Other: Arm E; BR-A-657 480mg or placebo	Drug: BR-A-657; 20, 60, 120, 240, 360, 480mg or placebo tablet; Other Names: Fimasartan; 20, 60, 120, 240, 360, 480mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
No of subjects with Adverse events(AE) from each observations	AE reporting: Pre dose, 3, 12, 24h, (48 h: Groups C, D, E) post dose; Vital signs: Pre dose*, 0.5, 1*, 2, 4*, 6, 8*, 12 and 24* h post dose (*:both supine and standing); ECG: Pre dose, 2, 4, 8 and 24 h post dose; Clinical laboratory examination: Pre dose and 24 h post dose; Physical examination: predose, 5~7days post dose; Body weight: predose, 5~7days post dose	up to 5~7days post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration time curve (AUC)	0.5,1,1.5,2,3,4,6,8,12,16,24,(48: Groups C, D, E)h
Maximum observed plasma concentration (Cmax)	0.5,1,1.5,2,3,4,6,8,12,16,24,(48: Groups C, D, E)h
Time of the maximum observed plasma concentration (Tmax)	0.5,1,1.5,2,3,4,6,8,12,16,24,(48: Groups C, D, E)h
Apparent total plasma clearance (CL/F)	0.5,1,1.5,2,3,4,6,8,12,16,24,(48: Groups C, D, E)h
Apparent plasma terminal elimination half life (t½)	0.5,1,1.5,2,3,4,6,8,12,16,24,(48: Groups C, D, E)h

Collaborators and Investigators

• Sponsor: Boryung Pharmaceutical Co., Ltd
• Collaborators: Covance
• Investigators: Principal Investigator: E Engmann, MB ChB, Covance Clinical Research Unit

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: December 13, 2010
• First Submitted That Met QC Criteria: February 3, 2011
• First Posted (Estimate): February 4, 2011

Study Record Updates

• Last Update Posted (Estimate): February 4, 2011
• Last Update Submitted That Met QC Criteria: February 3, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: safety; pharmacokinetic; pharmacodynamic; single-dose
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: 2290/2