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

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

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

Study Overview

• Status: Completed
• Conditions: Hypertension, Hyperlipidemia
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Clinical Trial Center, Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male of 20 to 45 years of age at screening
2. 19 kg/m2 ≤ BMI≤ 27 kg/m2 at screening
3. 90 mmHg ≤SBP<140 mmHg and 60 mmHg ≤DBP<90 mmHg at sitting position at screening

4. 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
5. 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:

1. A subject who has medical history of or has clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrinological, neurologic, hematologic/oncologic, or cardiovascular disease
2. A subject with severe renal insufficiency (CrCL < 10mL/min by Cockcroft-Gault estimation)
3. 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
4. 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
5. A subject with a history of drug abuse or a positive urine drug screen for barbiturate, benzodiazepine, methamphetamine, cannabinoids, cocaine, or opiate
6. 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)
7. A subject who has participated in any other clinical trial and received study drug within 60 days before the first drug administration
8. 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
9. A subject who has taken the drug which inhibits or induces drug metabolism such as barbital
10. A subject with unusual dietary habit which may influence on the administration, distribution, metabolism or excretion of drugs
11. A subject who consumes caffeine excessively (> 5 units/day)
12. A subject with consumes alcohol excessively (> 21 units/week, 1 unit = 10 mL of pure alcohol) or with a history of alcoholism
13. A heavy smoker ( >10 cigarettes/day)
14. A subject of positive result in serology tests (HBV, HCV, HIV, or syphilis)
15. A subject who has hereditary muscle disease or family history of hereditary muscle disease, or who has history of muscle disorder induced by drug
16. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valsartan 160mg, Rosuvastatin 20mg; 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); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor
Experimental: Rosuvastatin 20mg; 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); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor
Experimental: Valsartan 160mg; 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); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 2 : Period 1(V+R) Period 2(V) Period 3(R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 3 : Period 1(R) Period 2(V+R) Period 3(V); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 4 : Period 1(V+R) Period 2(R) Period 3(V); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 5 : Period 1(R) Period 2(V) Period 3(V+R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor; Drug: Sequence 6 : Period 1(V) Period 2(V+R) Period 3(R); Valsartan = Antihypertensive drug / Rosuvastatin = Antihyperlipidemic drug; Other Names: V= Valsartan = brand name : Diovan; R= Rosuvastatin = brand name : Crestor

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Adverse event monitoring; Clinical laboratory test; Vital signs; Electrocardiography; Physical examination	-1d and 1d, 2d, 3d, 4d, 5d, 6d, 7d, 8d, 9d, 10d of Period 1, 2, 3 and 42±2d

Collaborators and Investigators

• Sponsor: LG Life Sciences
• Investigators: Principal Investigator: Jae-Wook Ko, Professor, Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: August 6, 2013
• First Posted (Estimate): August 8, 2013

Study Record Updates

• Last Update Posted (Estimate): August 8, 2013
• Last Update Submitted That Met QC Criteria: August 6, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Rosuvastatin Calcium
• Other Study ID Numbers: LG-VRCL001