Healhty
Conditions
Brief summary
A randomized, open-label, two-sequence, two-period, multiple-dose, study to evaluate pharmacokinetic drug-drug interaction, safety and tolerability of UIC202304 and UIC202305 in healthy volunteers.
Interventions
DRUGUIC202304 and co-administration of UIC202304 and UIC202305
* UIC202304 1 Tab/day for 9 days * UIC202304 1 Tab/day + UIC202305 1 Tab/day for 7 days
DRUGUIC202305 and co-administration of UIC202304 and UIC202305
* UIC202305 1 Tab/day for 7 days * UIC202304 1 Tab/day + UIC202305 1 Tab/day for 9 days
Sponsors
Korea United Pharm. Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adult volunteers aged 19 years or older and younger than 55 years at the time of screening. 2. Male participants weighing at least 50 kg and female participants weighing at least 45 kg, with a body mass index, BMI, between 18.0 and 30.0 kg/m², inclusive. 3. Participants with no congenital or chronic diseases and no pathological symptoms or findings based on medical examination. 4. Participants who are judged by the investigator to be eligible for the study based on medical history, physical examination, clinical laboratory tests, and 12-lead electrocardiogram, ECG, performed within 4 weeks prior to the first administration of the investigational product, considering the characteristics of the investigational product. 5. Participants who are able to understand and comply with the study instructions and who are available to participate for the entire duration of the clinical trial. 6. Participants who agree to use contraception during the clinical trial and are able to comply with medically acceptable contraceptive methods, including a medically sterile or non-fertile condition. See Section 9.3.1 for acceptable contraceptive methods. 7. Participants who voluntarily decide to participate in the clinical trial after receiving and fully understanding a detailed explanation of the study and who provide written informed consent to comply with study requirements and precautions.
Exclusion criteria
1\. Medical History 1. Participants with a current or past history of clinically significant diseases involving the biliary system, including biliary obstructive disease; renal system, including severe renal impairment; hematologic or oncologic disorders; cardiovascular system, including congestive heart failure, coronary artery disease, aortic or mitral valve stenosis or related complications, arrhythmia, or renovascular hypertension; respiratory system, including asthma or chronic obstructive pulmonary disease; liver disease, including moderate or severe hepatic impairment; endocrine system, including diabetes mellitus, impaired glucose tolerance, hypothyroidism, or primary aldosteronism; gastrointestinal system; musculoskeletal system; central nervous system, including Parkinson's disease; psychiatric disorders; or malignant tumors. 2. Participants who are vulnerable to dehydration due to inadequate oral intake or who show clinically significant signs of dehydration. 3. Participants with a current or past history of gastrointestinal diseases that may affect drug absorption, including Crohn's disease, ulcer, gastritis, gastric spasm, gastroesophageal reflux disease, acute or chronic pancreatitis, or gastrointestinal surgery, except simple appendectomy or hernia repair. 4. Participants with hereditary angioedema or a history of angioedema during treatment with angiotensin-converting enzyme, ACE, inhibitors or angiotensin II receptor blockers. 5. Participants with a history of hypersensitivity or clinically significant hypersensitivity to amlodipine, telmisartan, atorvastatin, ezetimibe, drugs of similar classes, including other dihydropyridines, or other drugs, including aspirin or antibiotics. 6. Participants who have had a clinically significant disease within 30 days prior to the first administration of the investigational product. 2\. Clinical Laboratory Tests and Examinations 1. Participants who, after sufficient rest, show any of the following vital sign values measured in a sitting position: systolic blood pressure \>140 mmHg or \<100 mmHg, diastolic blood pressure \>90 mmHg or \<60 mmHg, or pulse rate \>100 beats/min or \<60 beats/min. 2. Participants with positive results for serologic tests, including hepatitis B, hepatitis C, syphilis, or human immunodeficiency virus, HIV. 3. Participants with serum AST, ALT, or total bilirubin levels greater than 1.5 times the upper limit of normal, ULN. 4. Participants with glomerular filtration rate, GFR, calculated using the Cockcroft-Gault formula, of \<60 mL/min. 5. Participants with creatine phosphokinase, CPK, levels increased to 5 times or more the upper limit of normal, ULN. 6. Participants with clinically significant findings on 12-lead electrocardiogram, ECG, or associated physical abnormalities or symptoms. 7. Participants who are judged by the investigator to be unsuitable for study participation based on physical examination or other findings. 3\. Allergy and Drug Abuse 1. Participants with genetic problems such as intolerance to the investigational product. 2. Participants with a history of drug abuse or a positive result for drugs of abuse in a drug screening test. 3. Participants with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 4\. Prohibited Concomitant Medications and Diet 1. Participants who have participated in another clinical trial within 180 days prior to the first administration of the investigational product. 2. Participants who have taken drugs that induce or inhibit drug metabolism, including CYP3A4 inducers or inhibitors, or drugs that inhibit drug transporters, including glecaprevir and pibrentasvir, within 28 days prior to the first administration of the investigational product. 3. Participants who have taken herbal medicines within 28 days, prescription drugs within 14 days, or over-the-counter drugs within 7 days prior to the first administration of the investigational product. However, participants may be allowed to participate in the clinical trial if the investigator determines that other conditions are appropriate. 4. Participants who have consumed grapefruit or grapefruit-containing foods within 7 days prior to the first administration of the investigational product, or who are unable to refrain from consuming them during the study period. 5\. Other Criteria 1. Participants who have donated whole blood within 60 days, donated blood components within 28 days, or received a blood transfusion within 28 days prior to the first administration of the investigational product. 2. Participants who have consumed excessive alcohol within 28 days prior to the first administration of the investigational product, defined as alcohol \>30 g/day; soju \>150 mL/day, based on 20% alcohol content; beer \>750 mL/day, based on 4% alcohol content; liquor \>75 mL/day, based on 40% alcohol content; or wine \>300 mL/day, based on 10% alcohol content. 3. Participants who have smoked excessively within 28 days prior to the first administration of the investigational product, defined as \>10 cigarettes/day, or who are unable to stop smoking during the clinical trial. 4. Participants who have consumed excessive caffeine within 28 days prior to the first administration of the investigational product, defined as coffee \>5 cups/day, tea \>1,250 mL/day, or cola \>1,250 mL/day. 5. Participants who continuously consume alcohol or are unable to abstain from alcohol during the clinical trial. 6. Female participants who are pregnant or breastfeeding. 7. Participants who are judged by the investigator or study physician to be unsuitable for participation in the clinical trial for any other reason, including clinical laboratory test results, withdrawal of consent prior to admission for Period 1, or excessive tattoos.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve Over a Dosing Interval at Steady State (AUCss,τ) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | AUCss,τ will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Maximum Plasma Concentration at Steady State (Css,max) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Css,max will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity at Steady State (AUCss,inf) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity at Steady State (AUCss,inf) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Time to Maximum Plasma Concentration at Steady State (Tss,max) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Time to Maximum Plasma Concentration at Steady State (Tss,max) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Elimination Half-Life at Steady State (tss,1/2) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Elimination Half-Life at Steady State (tss,1/2) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Minimum Plasma Concentration at Steady State (Css,min) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Minimum Plasma Concentration at Steady State (Css,min) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Apparent Total Body Clearance at Steady State (CLss/F) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Apparent Total Body Clearance at Steady State (CLss/F) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Apparent Volume of Distribution (Vd/F) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Apparent Volume of Distribution (Vd/F) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
| Peak-to-Trough Fluctuation at Steady State (PTF) | Predose (0 hour) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 9 and 16 for UIC202304 alone and with UIC202305, and on Days 7 and 16 for UIC202305 alone and with UIC202304. | Peak-to-Trough Fluctuation at Steady State (PTF) will be determined for amlodipine, telmisartan, atorvastatin, 2-hydroxy atorvastatin, total ezetimibe, and free ezetimibe. |
Countries
South Korea
Contacts
PRINCIPAL_INVESTIGATORSung-Dae Kwon, M.D.,Ph.D
Metro Hospital
Outcome results
None listed