Healthy
Conditions
Brief summary
A randomized open-label, multiple dose, three-treatment, three-period, six-sequence, crossover study to investigate the pharmacokinetic drug interaction between Atorvastatin and Ezetimibe after oral administration in healthy volunteers
Detailed description
Outcome Measures 1. Primary endpoint AUCτ,ss, Cmax,ss of atorvastatin and free ezetimibe 2. Second endpoint 1) AUCinf,ss, Cavg,ss, %fluctuation, tmax,ss, t1/2, CL/Fss, Vd/Fss of atorvastatin and free ezetimibe 2) AUCτ,ss, AUCinf,ss, Cmax,ss, tmax,ss, t1/2, metabolic ratio of 2-hydroxy atorvastatin and free ezetimibe
Interventions
DRUG1 (Lipitor®)
atorvastatin calcium 40mg, Lipitor® 40mg will be administered to healthy volunteers during 7days
DRUG1 (Ezetrol®)
After 11days withdrawal period, ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG1 (Lipitor®, Ezetrol®)
After 11days withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg and ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG2 (Ezetrol®)
ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG2(Lipitor®, Ezetrol®)
After 11days withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg and ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG2 (Lipitor®)
After 11day withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg will be administered to healthy volunteers during 7days
DRUG3(Lipitor®, Ezetrol®)
atorvastatin calcium 40mg, Lipitor® 40mg and ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG3 (Lipitor®)
After 11day withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg will be administered to healthy volunteers during 7days
DRUG3 (Ezetrol®)
After 11day withdrawal period, ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG4 (Lipitor®)
atorvastatin calcium 40mg, Lipitor® 40mg will be administered to healthy volunteers during 7days
DRUG4(Lipitor®, Ezetrol®)
After 11days withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg and ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG4 (Ezetrol®)
After 11day withdrawal period, ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG5 (Ezetrol®)
ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG5 (Lipitor®)
After 11day withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg will be administered to healthy volunteers during 7days
DRUG5 (Lipitor®, Ezetrol®)
After 11days withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg and ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG6(Lipitor®, Ezetrol®)
atorvastatin calcium 40mg, Lipitor® 40mg and ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG6 (Ezetrol®)
After 11days withdrawal period, ezetimibe 10mg, Ezetrol® 10mg will be administered to healthy volunteers during 7days
DRUG6 (Lipitor®)
After 11day withdrawal period, atorvastatin calcium 40mg, Lipitor® 40mg will be administered to healthy volunteers during 7days
Sponsors
Chong Kun Dang Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age Eligible for Study : 19 Years to 45 Years 2. If males, Body weight ≥ 55kg, If females, Body weight ≥ 50kg 3. BSA ≥ 18.5, \<25 4. Accepts healthy volunteers 5. If female, Negative for pregnancy test at the screening and pre dose of Day 1 6. The subjects who agree with performing contraception during the study 7. The subjects who agreed with written informed consent
Exclusion criteria
1. The subjects with impaired hepatic function, renal function, nervous system etc. 2. The subjects have a gastrointestinal disease or surgery which can be effected in absorption of Investigational product 3. The subjects with high blood pressure or low blood pressure (Systolic blood pressure\>150mmHg or \<90mmHg, Diastolic blood pressure\>100mmHg or \<50mmHg 4. The subjects with abnormal Laboratory test (AST, ALT\>1.25 fold of upper normal limit, Total bilirubin\>1.5 fold of upper normal limit, CPK\>2 fold of upper normal limit, Estimated Glomerular filtration rate\<60mL/min/1.73m2 by Modification of Diet in Renal disease formula 5. The subjects have drug abuse history within 1year or Positive for urine drug test at screening 6. The subjects who took prescription only medicine whch can be effected in metabolism of Investigational product within 14days 7. The subjects who took over the counter drug whch can be effected in metabolism of Investigational product within 7days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUCτ,ss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| Cmax,ss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| %fluctuation of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| tmax,ss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| t1/2 of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| CL/Fss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| Vd/Fss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| AUCinf,ss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| AUCinf,ss of 2-hydroxy atorvastatin and total ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| Cmax,ss of 2-hydroxy atorvastatin and total ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| tmax,ss of 2-hydroxy atorvastatin and total ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| t1/2 of 2-hydroxy atorvastatin and total ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| metabolic ratio of 2-hydroxy atorvastatin and total ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| AUCτ,ss of 2-hydroxy atorvastatin and total ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
| Cavg,ss of atorvastatin and free ezetimibe | common : just before the IP administration of D5(D22, D39), D6(D23, D40) | Atorvastatin single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 h Ezetimibe single : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h Atorvastatin+Ezetimibe : just before the IP administration of D7(D24, D41) and after the IP administration 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 h |
Countries
South Korea
Outcome results
None listed