A Study to Evaluate Drug-drug Interactions Between BR9006-1 and BR9006-2 in Healthy Male Volunteers.

Study Overview
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Brief Summary
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To evaluate the influence of BR9006-1 and BR9006-2 on pharmacokinetics, safety, and tolerability when administered separately or co-administered to healthy male volunteers.

Detailed Description
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A total of 36 subjects will be enrolled in one sequence group. The investigational products will be administered according to the treatment groups (T, M, T+M) assigned to one sequence group in Period 1, Period 2, and Period 3.

Official Title
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An Open Label, One-sequence, 3-period Study to Evaluate Drug-drug Interactions Between BR9006-1 and BR9006-2 in Healthy Male Volunteers.

Conditions
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Benign Prostatic Hyperplasia (BPH), Overactive Bladder

Intervention / Treatment
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* Drug: BR9006-1
* Drug: BR9006-2


Participation Criteria
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Eligibility Criteria
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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 male adults aged 19 to 55 years at screening. The subject's weight is 50kg or more and body mass index (BMI) is 18.0 or more but 30.0 or less. Exclusion Criteria: Those who have history of clinically significant diseases including hypersensitivity reaction, intolerability and anaphylaxis to major ingredients (Tamsulosin and Mirabegron) and other ingredients of investigational products, Food Yellow No. 5 (Sunset Yellow FCF) or Sulfonamide. 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 (MDRD method used) Those with systolic blood pressure > 150 mmHg or < 90 mmHg, or diastolic blood pressure > 95 mmHg or < 60 mmHg from vital signs at screening. Those who took drugs (prescription drugs, OTC, herbal medicine or nutritional supplements (vitamins, etc.)) 2 weeks before screening. (However, those may participate in the trial if their safety and study results are considered to be unaffected according to the investigator's judgment.) Those who have a drug abuse problem (especially centrally acting drugs including sleeping pills, centrally acting pain reliever, opiates or psychoactive drugs) or have a history of drug abuse. Those who have a history of continuous alcohol intake exceeding 21 units/week (1unit=10g=12.5mL) within 6 months before screening. Those who have smoked more than 10 cigarettes a day within 6 months before screening. Those who have participated in other clinical trials and have been administered with other investigational drugs 180 days prior to the estimated administration date of this study's investigational drugs (However, is not applicable if the investigational drugs from other trials are not administered). Those who have given whole blood 8 weeks before screening, who have given plasma/platelet 4 weeks before screening or who have not expressed their consent for blood-donation prohibition between the period from the first administration and 30 days after the final administration of the investigational drugs. Those who have not expressed their consent for diet restrictions (grapefruit, caffeine in particular) that can influence absorption, distribution, metabolism and excretion of investigational drugs in the period between 3 days before the first administration and the last visit. Those who have not expressed their consent for using contraceptive measures (for example: contraceptive administration and implant or intrauterine devices, sterilization (vasectomy, tubal ligation, etc.)) and barrier methods (combined use of spermicides and condom, contraceptive vaginal diaphragm, contraceptive sponge or cervical cap) that are allowed for clinical trials in the period between the first administration of the investigational drugs and the last visit. Others who are judged to be ineligible to participate in the trial by the investigator.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence T/M/T+M<br>A total of 36 subjects will be enrolled in one sequence group. The investigational products (IPs) will be administered according to the treatment groups(T, M, T+M) assigned to on sequence group in Period 1, Period 2, and Period 3. Period 1(T): BR9006-1 (Tamsulosin HCL 0.2mg) - 1 capsule QD, five-day repeated-dose Period 2(M): BR9006-2 (Mirabegron 50mg) - 1 tablet QD, eleven-day repeated-dose Period 3(T+M): BR9006-1 (Tamsulosin HCL 0.2mg) 1 capsule + BR9006-2 (Mirabegron 50mg) 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: none | Drug: BR9006-1<br>* Administration to the T/T+M group: 0.2 mg of BR9006-1 will be administered one capsule once a day, five-day repeated-dose<br>* Other names: Tamsulosin HCL;Drug: BR9006-2<br>* Administration to the M group: 50 mg of BR9006-2 will be administered one tablet once a day, eleven-day repeated-dose Administration to the T+M group: 50 mg of BR9006-2 will be administered one tablet once a day, five-day repeated-dose<br>* Other names: Mirabegron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables - Maximum (peak) steady-state plasma drug concentration during a dosage interval(Cmax,ss) of Part A and B | The analysis to investigate drug-drug interaction shall be divided into two parts: Part A (Tamsulosin vs. Tamsulosin + Mirabegron) and Part B (Mirabegron vs. Mirabegron + Tamsulosin). | 0 26 days after medication | 
| Pharmacokinetic variables - Area under the plasma concentration-time curve from time zero to time t(AUCt) of Part A and B | The analysis to investigate drug-drug interaction shall be divided into two parts: Part A (Tamsulosin vs. Tamsulosin + Mirabegron) and Part B (Mirabegron vs. Mirabegron + Tamsulosin). | 0 26 days after medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variables - Time to reach maximum (peak) plasma concentration following drug administration at steady state (Tmax,ss) of Part A and B | The analysis to investigate drug-drug interaction shall be divided into two parts: Part A (Tamsulosin vs. Tamsulosin + Mirabegron) and Part B (Mirabegron vs. Mirabegron + Tamsulosin). | 0 26 days after medication | 
| Pharmacokinetic variables - Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss) of Part A and B | The analysis to investigate drug-drug interaction shall be divided into two parts: Part A (Tamsulosin vs. Tamsulosin + Mirabegron) and Part B (Mirabegron vs. Mirabegron + Tamsulosin). | 0 26 days after medication |