Drug Interaction and Safety Between Valsartan and Rosuvastatin in Healthy Male Volunteers

Study Overview
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Brief Summary
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Primary objective : To investigate pharmacokinetics after concomitant administration of valsartan and rosuvastatin compared to single administration of valsartan or rosuvastatin in healthy male volunteers Secondary objective : To investigate safety profiles after the administration of valsartan or rosuvastatin alone and concomitant administration of valsartan and rosuvastatin in healthy male volunteers

Official Title
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A Randomized, Open Label, Multiple Dose, Cross-over, Phase I Trial to Evaluate a Pharmacokinetic Drug Interaction and Safety Between Valsartan and Rosuvastatin in Healthy Male Volunteers

Conditions
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Hypertension, Hyperlipidemia

Intervention / Treatment
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* Drug: Sequence 1 : Period 1(V) Period 2(R) Period 3(V+R)
* Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R)
* Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V)
* Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V)
* Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R)
* Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male of 20 to 45 years of age at screening 19 kg/m2 ≤ BMI≤ 27 kg/m2 at screening 90 mmHg ≤SBP<140 mmHg and 60 mmHg ≤DBP<90 mmHg at sitting position at screening At screening AST and ALT ≤ 1.5 times of upper normal limit Serum total bilirubin ≤ 1.5 times of upper normal limit CK ≤ 2 times of upper normal limit A subject who is able to understand the study, to participate whole periods of the study and to provide written informed consent voluntarily after being fully informed of the study objectives, procedures and study drug Exclusion Criteria: A subject who has medical history of or has clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrinological, neurologic, hematologic/oncologic, or cardiovascular disease A subject with severe renal insufficiency (CrCL < 10mL/min by Cockcroft-Gault estimation) A subject with a history of gastrointestinal disease (e.g., ulcer, Crohn's disease) or surgery (except a simple appendectomy or repair of a hernia) that may influence the absorption of the study drug A subject with a history of drug allergies to valsartan, rosuvastatin, or other drugs (e.g., aspirin, antibiotics), or a history of clinically significant allergies A subject with a history of drug abuse or a positive urine drug screen for barbiturate, benzodiazepine, methamphetamine, cannabinoids, cocaine, or opiate A subject who has taken any prescribed medication or herbal compounds within 14 days before the first drug administration. In addition, a subject who has taken any over-the-counter drug or vitamin supplement within 7 days before the first drug administration. (However, investigators made the final decision on the eligibility for the trial if all other conditions were satisfied) A subject who has participated in any other clinical trial and received study drug within 60 days before the first drug administration A subject who has donated a unit of blood or blood components within 60 days or 30 days, respectively, or received a transfusion before the first drug administration A subject who has taken the drug which inhibits or induces drug metabolism such as barbital A subject with unusual dietary habit which may influence on the administration, distribution, metabolism or excretion of drugs A subject who consumes caffeine excessively (> 5 units/day) A subject with consumes alcohol excessively (> 21 units/week, 1 unit = 10 mL of pure alcohol) or with a history of alcoholism A heavy smoker ( >10 cigarettes/day) A subject of positive result in serology tests (HBV, HCV, HIV, or syphilis) A subject who has hereditary muscle disease or family history of hereditary muscle disease, or who has history of muscle disorder induced by drug The investigator determines whether or not the subject is eligible for the study after, for example, reviewing clinical laboratory results, ECG result, or for other reason

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan 160mg, Rosuvastatin 20mg<br>Both Valsartan 160mg and Rosuvastatin 20mg are administered daily by mouth once a day for 7 days. | Drug: Sequence 1 : Period 1(V) Period 2(R) Period 3(V+R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;|
| Experimental: Rosuvastatin 20mg<br>Rosuvastatin 20mg is administered daily by mouth once a day for 7 days. | Drug: Sequence 1 : Period 1(V) Period 2(R) Period 3(V+R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;|
| Experimental: Valsartan 160mg<br>Valsartan 160mg is administered daily by mouth once a day for 7 days. | Drug: Sequence 1 : Period 1(V) Period 2(R) Period 3(V+R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R)<br>* Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug<br>* Other names: R= Rosuvastatin = brand name : Crestor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of valsartan and rosuvastatin | Cmax,ss and AUCτ,ss of valsartan and rosuvastatin | 0h (pre-dosing on 6d, 20d, 34d) and 0h (pre-dosing), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 16h, 24h, 48h, and 72h (on 7d, 21d, 35d). Day 1 0h (only in period 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of valsartan and rosuvastatin | Tmax,ss, Cmin,ss, t1/2,β of valsartan and rosuvastatin Cmax,ss and AUCτ,ss of N-desmethyl rosuvastatin | 0h (pre-dosing on 6d, 20d, 34d) and 0h (pre-dosing), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 16h, 24h, 48h, and 72h (on 7d, 21d, 35d). Day 1 0h (only in period 1) |