Pharmacokinetic Interactions Between Amlodipine Besylate/Valsartan and Atorvastatin in Healthy Male Subjects

An Open-label, Multiple-dosing, Two-arms, One-sequence Study to Evaluate the Safety and Pharmacokinetics After Co-administration of Exforge® (Amlodipine Besylate/Valsartan) and Lipitor® (Atorvastatin Ca) in Healthy Male Volunteers

The purpose of the study is to assess the pharmacokinetic interactions between amlodipine besylate/valsartan and atorvastatin single or co-administered in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: combination administration

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jung-gu
    • Daejeon, Jung-gu, Korea, Republic of, 301-721
      • Chungnam National University Hospital

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. Male volunteers in the age between 20 and 45 years old
2. The weight is over 55kg and is not exceed ±20% of ideal weight Ideal weight = [height -100]*0.9
3. Subjects with no history of any significant chronic disease
4. Judged to be in good health on the basis of routine laboratory data obtained prior to study drug administration
5. Willing to adhere to protocol requirements and sign a informed consent form

Exclusion Criteria:

1. Subjects with Symptoms of acute disease within 28days prior to study medication dosing
2. Subjects with a history of gastrointestinal diseases which might significantly change ADME of medicines
3. Subjects with a history of clinically significant allergies including drug allergies or anaphylaxis to amlodipine, valsartan and/or atorvastatin
4. Subjects with a history of myopathy
5. Subjects with a hereditary problems, for example, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
6. Subject with the mean blood pressure of siDBP ≥ 150 mmHg or ≤ 90 mmHg and/or siSBP ≥ 95 mmHg or ≤ 50 mmHg at the screening visit
7. Subjects with abnormal HDL-cholesterol(<35mg/dL)
8. Subjects with abnormal of serum potassium concentration (<3.4 mEq/L of >5.5 mEq/L in screening visit)
9. Subjects with a history of drug abuse
10. Subjects taking inducer or inhibitor of drug metabolism enzyme such as barbital within 28days prior to study medication dosing
11. Subjects who have received any drugs that might confound the results of the trial based on medical judgement by investigators within 14days prior to drug administration and OTC or vitamin within 7days prior to drug administration
12. Participated in a previous clinical trial within 60 days prior to dosing
13. Donated blood within 60 days prior to dosing
14. Subjects with a history of alcohol abuse(over 21 units/week, 1 unit = 10 g of pure alcohol) or is difficult to stop drinking within study
15. Subjects have ever smoked over 10 cigarette per day within 3 months prior to drug administration
16. Subjects with a history of caffeine abuse or or is difficult to stop drinking within study
17. Subjects with biliary obstruction
18. Subjects with hepatic dysfunction (AST or ALT >3 times to accepted normal range)
19. Subjects with moderate renal dysfunction (creatinine clearance (CLcr) < 30mL/min)
20. Subjects considered as unsuitable based on medical judgement by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; single administration : amlodipine/valsartan 10/160mg, qd, 10days(oral)	Drug: combination administration; combination administration : amlodipine/valsartan 10/160mg and atorvastatin 40mg, qd, 10days(oral)
Experimental: Group B; single administration : atorvastatin 40mg, qd, 7days(oral)	Drug: combination administration; combination administration : amlodipine/valsartan 10/160mg and atorvastatin 40mg, qd, 10days(oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate PK interaction of amlodipine and valsartan	AUCss,τ, Css,max	from pre dosing to 24hr post dose
To Evaluate PK interaction of atorvastatin and 2-OH atorvastatin	AUCss,τ, Css,max	from pre dosing to 24hr post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate PK interaction of amlodipine and valsartan	tss,max, CLss/F, Css,min	from pre dosing to 24hr post dose
To Evaluate PK interaction of atorvastatin and 2-OH atorvastatin	tss,max, CLss/F, Css,min	from pre dosing to 24hr post dose

Collaborators and Investigators

• Sponsor: HK inno.N Corporation

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: February 19, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 24, 2014

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: CJ_EXA_101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO