Safety and Pharmacokinetics Between Fixed-dose Combination VR 160/20 mg and Co-administration of Diovan® (Valsartan) Film-coated Tablet 160 mg and Crestor® (Rosuvastatin) 20 mg

A Randomized, Open-label, Single Dose Crossover Study to Compare the Safety and Pharmacokinetics Between Fixed-dose Combination VR 160/20 mg and Co-administration of Diovan® (Valsartan) Film-coated Tablet 160 mg and Crestor® (Rosuvastatin) 20 mg in Healthy Male Volunteers

To compare the safety and pharmacokinetics between ROVATITAN tab. 160/20 mg (ROVATITAN tab 160/20mg-1, ROVATITAN tab. 160/20mg-2) and coadministration of Diovan® (Valsartan) 160 mg and Crestor® (Rosuvastatin) 20 mg in healthy male volunteers

Study Overview

• Status: Completed
• Conditions: Hypertension; Hyperlipidemia
• Intervention / Treatment: Drug: Sequence 1 : Period 1 (VR 160/20 mg-1), Period 2(VR 160/20 mg-2), Period (V+R); Drug: Sequence 2 : Period 1 (VR 160/20 mg-2), Period 2 (V+R), Period 3 (VR 160/20 mg-1); Drug: Sequence 3 : Period 1 (V+R), Period 2 (VR 160/20 mg-2), Period 3 (VR 160/20 mg-1); Drug: Sequence 4 : Period 1 (VR 160/20 mg-1), Period 2 (V+R), Period 3 (VR 160/20 mg-2 ); Drug: Sequence 5 : Period 1 (VR 160/20 mg-2), Period 2 (VR 160/20 mg-1), Period 3 (V+R ); Drug: Sequence 6 : Period 1 (V+R), Period 2 (VR 160/20 mg-1), Period 3 (VR 160/20 mg-2)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male aged 20~45 years at screening
2. 19 kg/m2 ≤ BMI ≤27 kg/m2 at screening
3. Subject who is able to communicate with investigators and understand the nature of the clinical study and is willing and able to provide a written informed consent form

Exclusion Criteria:

1. Subject with current or previous clinically significant diseases in liver, renal, neurologic, pulmonary, gastrointestinal, endocrine, hematologic, oncologic, cardiovascular, psychological, and musculoskeletal system
2. Patient with renal defects (Calculated GFR < 60 ml/min based on serum creatinine level )
3. Subject who can not satisfy the following criteria for sitting blood pressure at screening test 90 ≤SBP <140 (mmHg) 60 ≤ DBP <90 (mmHg)
4. Subject who can not satisfy the following criteria at screening 1) AST and ALT ≤ 1.5x ULN 2) Serum total bilirubin ≤ 1.5x ULN 3) CK (Creatinine kinase) ≤ 2x ULN
5. Subject with a medical history of gastrointestinal diseases (e.g., Crohn's disease, ulcer) or a surgery (for appendicitis and hernia repair are allowed) that might affect the investigational product absorption
6. Subject with hypersensitivity to the drugs containing components of valsartan and rosuvastatin or other drugs (aspirin, antibiotics) or a previous clinically significant history of hypersensitivity
7. Subject with a previous history of drug overdose or a positive to the drugs (Barbiturate, Benzodiazepine, Methamphetamine, Cannabinoids, Cocaine, Opiate) in urine drug screening test
8. Subject who has taken any prescribed medicines or oriental medicines within two weeks before the first investigational product administration, or who has taken any over-the-counter drugs within one week before the first investigational product administration (If the subject is eligible for all other criteria, he or she may participate in the clinical study based on investigator's discretion.)
9. Subject who has taken other investigational products within 60 days before the first investigational product administration
10. Subject who donated whole blood within 60 days or donated apheresis blood within 30 days or received a transfusion within 30 days before the first investigational product administaration.
11. Subject who has taken the drugs that induce or inhibit drug-metabolizing enzymes such as barbiturates within 30 days before the first investigational product administration
12. Subject with a daily intake of drinks containing caffeine (coffee, tea, coke) or grapefruit juice > average of 4 cups / day (800 mL) or a subject who can not discontinue such drinks during the clinical study period(from screening to post-study visit)
13. Subject with a mean weekly drinking amount of > 140g or a subject who can not stop drinking until outpatient visit after the investigational product administration, including the hospitalization in each period.
14. Subject with a mean daily smoking amount of > 10 cigarettes or a subject who can not stop smoking during the hospitalization
15. Subject positive result in serology tests (hepatitis B, hepatitis C, HIV)
16. Subject with genetic muscle disease, or familial history of muscle disease, or medical history of drug-derived muscle disorder
17. Subject who is considered not to be eligible at investigator's discretion.

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: Fixed-dose combination VR 160/20 mg-1; Fixed-dose combination VR 160/20 mg-1 is administered by mouth at Day 1, 8 and 15.	Drug: Sequence 1 : Period 1 (VR 160/20 mg-1), Period 2(VR 160/20 mg-2), Period (V+R); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 2 : Period 1 (VR 160/20 mg-2), Period 2 (V+R), Period 3 (VR 160/20 mg-1); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 3 : Period 1 (V+R), Period 2 (VR 160/20 mg-2), Period 3 (VR 160/20 mg-1); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 4 : Period 1 (VR 160/20 mg-1), Period 2 (V+R), Period 3 (VR 160/20 mg-2 ); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 5 : Period 1 (VR 160/20 mg-2), Period 2 (VR 160/20 mg-1), Period 3 (V+R ); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 6 : Period 1 (V+R), Period 2 (VR 160/20 mg-1), Period 3 (VR 160/20 mg-2); Other Names: Crestor; Diovan; Rovatitan tab
Experimental: Fixed-dose combination VR 160/20 mg-2; Fixed-dose combination VR 160/20 mg-2 is administered by mouth at Day 1, 8 and 15.	Drug: Sequence 1 : Period 1 (VR 160/20 mg-1), Period 2(VR 160/20 mg-2), Period (V+R); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 2 : Period 1 (VR 160/20 mg-2), Period 2 (V+R), Period 3 (VR 160/20 mg-1); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 3 : Period 1 (V+R), Period 2 (VR 160/20 mg-2), Period 3 (VR 160/20 mg-1); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 4 : Period 1 (VR 160/20 mg-1), Period 2 (V+R), Period 3 (VR 160/20 mg-2 ); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 5 : Period 1 (VR 160/20 mg-2), Period 2 (VR 160/20 mg-1), Period 3 (V+R ); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 6 : Period 1 (V+R), Period 2 (VR 160/20 mg-1), Period 3 (VR 160/20 mg-2); Other Names: Crestor; Diovan; Rovatitan tab
Experimental: Valsartan 160mg placebo + Rosuvastatin 20mg; Both Valsartan 160mg placebo and Rosuvastatin 20mg are administered by mouth at Day 1, 8 and 15.	Drug: Sequence 1 : Period 1 (VR 160/20 mg-1), Period 2(VR 160/20 mg-2), Period (V+R); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 2 : Period 1 (VR 160/20 mg-2), Period 2 (V+R), Period 3 (VR 160/20 mg-1); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 3 : Period 1 (V+R), Period 2 (VR 160/20 mg-2), Period 3 (VR 160/20 mg-1); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 4 : Period 1 (VR 160/20 mg-1), Period 2 (V+R), Period 3 (VR 160/20 mg-2 ); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 5 : Period 1 (VR 160/20 mg-2), Period 2 (VR 160/20 mg-1), Period 3 (V+R ); Other Names: Crestor; Diovan; Rovatitan tab; Drug: Sequence 6 : Period 1 (V+R), Period 2 (VR 160/20 mg-1), Period 3 (VR 160/20 mg-2); Other Names: Crestor; Diovan; Rovatitan tab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of valsartan and rosuvastatin	0h(pre-dosing), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 6h, 8h, 12h, 24h, 48h for each period (total 16 times)
AUC last of valsartan and rosuvastatin	0h(pre-dosing), 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 6h, 8h, 12h, 24h, 48h for each period (total 16 times)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation	The severity of adverse events and their relationship with the investigational products are schematized by treatment group. Descriptive statistics are calculated for the frequency, percentage, 12-lead ECG and clinical laboratory tests results of the subjects who have adverse events and the results of each item are reviewed.	-28~-2d, 1d, 2d, 3d, 8d, 9d, 10d, 15d, 16d, 17d, 21 ± 2d

Collaborators and Investigators

• Sponsor: LG Life Sciences

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: August 5, 2013
• First Submitted That Met QC Criteria: August 6, 2013
• First Posted (Estimate): August 7, 2013

Study Record Updates

• Last Update Posted (Estimate): August 7, 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-VRCL005