A Clinical Trial to Evaluate Drug-drug Interactions and Safety Between "BR1015-1" and "BR1015-2" in Healthy Volunteers

An Open-label, One-sequence, 3-period Study to Evaluate Drug-drug Interactions and Safety Between "BR1015-1" and "BR1015-2" in Healthy Volunteers.

The purpose of this study is to evaluate pharmacokinetic interactions (Drug-Drug interaction) and safety between "BR1015-1" and "BR1015-2" in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: BR1015-1; Drug: BR1015-2; Drug: BR1015-1 + BR1015-2

Detailed Description

*Study Objective: After repeated administration of BR1015-1 and BR1015-2 for healthy volunteers, the pharmacokinetic interactions and safety are evaluated.

*Investigational Product (and regimen)

1. BR1015-1: Administration of BR1015-1 60 mg once a day for 5 days
2. BR1015-2: Administration of BR1015-2 1.5 mg once a day for 5 days
3. BR1015-1+BR1015-2: Co-administration of BR1015-1 60 mg and BR1015-2 1.5 mg once a day for 5 days

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam-si
    • Gyeonggi-do, Seongnam-si, Korea, Republic of, 13520
      • CHA Bundang Medical Center, CHA University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects are given sufficient explanations about the trial objectives and contents as well as properties of investigational drugs before participating in the trial, and will voluntarily express their consent by signing an IRB-approved written consent to participate in the trial.
• Healthy adults aged 19 to 55 years at screening.
• The subject's weight is 50 kg or more for males, 45 kg or more for females, and body mass index (BMI) is 18.0 or more but 30.0 kg/m2 or less.

Exclusion Criteria:

• Those who have history of clinically significant diseases including hypersensitivity reaction, intolerability and anaphylaxis to major ingredients and other ingredients of investigational products.
• Those who have history of clinically significant diseases including allergy reaction to Yellow No. 5 (Sunset Yellow FCF).
• Those who have a history of clinically significant diseases related to liver, kidney, digestive system, respiratory system, musculoskeletal system, endocrine system, neuropsychiatric system, hemato-oncology system, cardiovascular system (including orthostatic hypotension), etc.
• Those who have medical history of gastrointestinal system diseases (for example: Crohn's disease, peptic ulcer disease, etc.) and operations that may influence the absorption of investigational drugs. (However, appendectomy, hernia operation, endoscopic polypectomy and hemorrhoids/anal fissure/anal fistula surgeries are excluded.)
• Those with abnormal findings from the screening tests (medical interview, vital signs, electrocardiography, physical checkup, blood test, urinalysis, etc.) are judged to have clinical significance.
• Those who are positive to HBsAg, HCV Ab, HIV Ab, VDRL tests at screening.
• Those with any of the following results at screening:
• AST or ALT > twice the upper limit of normal range
• T. bilirubin > twice the upper limit of normal range
• Estimated glomerular filtration rate (e-GFR) < 60 mL/min/1.73m2 (CKD-EPI method used)
• Na > 150 mEq/L or <130 mEq/L
• K > 5.5 mEq/L or <3.0 mEq/L
• Those with systolic blood pressure > 160 mmHg or < 110 mmHg, or diastolic blood pressure > 100 mmHg or < 70 mmHg from vital signs at screening.
• Others who are judged to be ineligible to participate in the trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sequence BR1015-1/BR1015-2/BR1015-1 + BR1015-2; A total of 32 subjects will be enrolled in one sequence group. The investigational products (IPs) will be administered according to the treatment groups(BR1015-1, BR1015-2, BR1015-1 + BR1015-2) assigned to one sequence group in Period 1, Period 2, and Period 3.; Period 1(BR1015-1): BR1015-1(Fimasartan 60mg) - 1 tablet QD, five-day repeated-dose; Period 2(BR1015-2): BR1015-2(Indapamide 1.5mg) - 1 tablet QD, five-day repeated-dose; Period 3(BR1015-1 + BR1015-2): BR1015-1 (Fimasartan 60mg) 1 tablet + BR1015-2 (Indapamide 1.5mg) 1 tablet QD, five-day repeated-dose; Washout period between Period 1 and Period 2: five days; Washout period between Period 2 and Period 3: two days

Drug: BR1015-1; - Administration to the BR1015-1 group: 60 mg of BR1015-1 will be administered one tablet once a day, five-day repeated doses.; Other Names: Fimasartan 60 mg; Drug: BR1015-2; - Administration to the BR1015-2 group: 1.5 mg of BR1015-2 will be administered one tablet once a day, five-day repeated doses.; Other Names: Indapamide 1.5 mg; Drug: BR1015-1 + BR1015-2; - Co-administration to the BR1015-1+BR1015-2 group: 60 mg of BR1015-1 one tablet and 1.5 mg of BR1015-2 one tablet will be co-administered once a day, five-day repeated doses.; Other Names: Fimasartan and Indapamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Part A] Cmax,ss of BR1015-1	Pharmacokinetic variables - Maximum (peak) plasma concentration of BR1015-1 at steady state (Cmax,ss).	0~24 hour after administration at Day 5.
[Part B] Cmax,ss of BR1015-2	Pharmacokinetic variables - Maximum (peak) plasma concentration of BR1015-2 at steady state (Cmax,ss).	0~24 hour after administration at Day 5.
[Part A] AUCtau of BR1015-1	Pharmacokinetic variables - Area under the plasma drug concentration-time curve to the end of the dosing period in multiple dosing of BR1015-1 at steady state. (AUCtau,ss)	0~24 hour after administration at Day 5.
[Part B] AUCtau of BR1015-2	Pharmacokinetic variables - Area under the plasma drug concentration-time curve to the end of the dosing period in multiple dosing of BR1015-2 at steady state. (AUCtau,ss)	0~24 hour after administration at Day 5.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Part A] AUClast of BR1015-1	Area under the plasma drug concentration-time curve over the time interval from 0 to the last quantifiable plasma concentration (AUClast) of BR1015-1	0~48 hour after administration
[Part B] AUClast of BR1015-2	Area under the plasma drug concentration-time curve over the time interval from 0 to the last quantifiable plasma concentration (AUClast) of BR1015-2	0~48 hour after administration
[Part A] AUCinf of BR1015-1	Area under the plasma drug concentration-time curve over the time interval from 0 extrapolated to infinity of BR1015-1	0~48 hour after administration
[Part B] AUCinf of BR1015-2	Area under the plasma drug concentration-time curve over the time interval from 0 extrapolated to infinity of BR1015-2	0~48 hour after administration
[Part A] Tmax of BR1015-1	Time to reach maximum (peak) plasma concentration following drug administration at steady state (Tmax,ss)	0~24 hour after administration
[Part B] Tmax of BR1015-2	Time to reach maximum (peak) plasma concentration following drug administration at steady state (Tmax,ss)	0~24 hour after administration
[Part A] t1/2 of BR1015-1	Terminal half-life of BR1015-1	0~48 hour after administration
[Part B] t1/2 of BR1015-2	Terminal half-life of BR1015-2	0~48 hour after administration

Collaborators and Investigators

• Sponsor: Boryung Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: An-Hye Kim, M.D. Ph.D, CHA University

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): October 22, 2021
• Study Completion (Actual): October 22, 2021

Study Registration Dates

• First Submitted: October 17, 2021
• First Submitted That Met QC Criteria: October 17, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Indapamide
• Other Study ID Numbers: BR-FMS-CT-118

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No