Study to Investigate the Effect of Telmisartan/S-amlodipine on the Pharmacokinetic Properties of Atorvastatin. (CKD-345)

A Randomized, Open-label, Single Dose, Two-treatment, Two-period, Two-sequence Crossover Study to Investigate the Effect of Telmisartan/S-amlodipine on the Pharmacokinetic Properties of Atorvastatin After Oral Administration in Healthy Volunteers

The purpose of this study is to investigate the effect of telmisartan/s-amlodipine on the pharmacokinetic properties of atorvastatin.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension; Hyperlipidemia
• Intervention / Treatment: Drug: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg; Drug: atorvastatin 40mg

Detailed Description

healthy subjects are administrated single-dose over the period Ⅰand Ⅱ(Crossover) of telmisartan/s-amlodipine, atorvastatin and atorvastatin.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Between 20 aged and 45 aged in healthy male and female
2. Body weight more than 55kg in male, 50kg in female
3. Body Mass Index more than 18.5 and under 25 (Body Mass Index(kg/m2)= kg/(m)2)

4. If female, must include more than one among the items

   1. The menopause (there is no natural menses for at least 2 years)
   2. Surgical Infertility(hysterectomy or bilateral oophorectomy, tubal ligation or other methods of infertility condition)
   3. The male partner infertility before screening (Demonstrated azoospermia after vasectomy)and if this man is the only partner of the female subject.

   4. you are using one of the following contraceptive measure for 3 months before screening, and Necessarily you agree that used continuously contraceptive measure during the clinical trial and for 1 month after the final dosing investigational product.(But, should not use a device of contraception or oral contraceptive drug that containing a hormonal caused telmisartan, s-amlodipine, atorvastatin calcium drug interactions during the clinical trials)

      • Abstinence.
      • Physical interrupt method (such as a condom, contraceptive diaphoretic or cervical cap)
   5. In case of women of childbearing age, the serum β-hCG pregnancy test is negative, and urine β-hCG test is negative before taking the investigational product.
5. If men has sexual life with women of childbearing age, Necessarily he agrees that use condoms during clinical trials and do not sperm donation during clinical trials and until one month after the final dosage of investigational products
6. Those who fully understand about this clinical trial after enough hearing, and then decided to join the clinical trials by themselves and to comply with the precautions written consent.

Exclusion Criteria:

1. Have clinically significant disease that hepatobiliary system(severe hepatic impairment, etc), kidney(severe renal impairment, etc.), nervous system, immune system, respiratory system, endocrine system,hemato-oncology disease, cardiovascular system (heart failure, etc.).or mental illness, or a history of mental disease.
2. Have a gastrointestinal disease history that can affect drug absorption (Crohn, ulcers, etc.) or surgery (except simple appendectomy or hernia surgery)
3. Hypersensitivity reaction to drug or clinically significant hypersensitivity reaction in the history of Investigational drugs (telmisartan, s-amlodipine or atorvastatin calcium) or additives
4. An impossible one who participates in clinical trial including screening tests(medical history taking, BP, physical examination, 12-lead ECG, blood & urine laboratory test result) within 28 days before the beginning of study treatment.

5. Defined by the following laboratory parameters:

   • AST, ALT> 1.25*upper limit of normal range
   • Total bilirubin > 1.5* upper limit of normal range
   • CPK > 1.5* upper limit of normal range
   • eGFR(using by MDRD method) < 60 mL/min/1.73m2
6. Sitting SBP > 150 mmHg or < 90 mmHg, Sitting DBP> 100 mmHg or < 50 mmHg , after 5minuts break.
7. Drug abuse or have a history of drug abuse showed a positive for the Triage TOX drug on urine.
8. Pregnant or lactating women.
9. A heavy caffeine consumer(caffeine>5cups/day), alcohol consumer(alcohol>210g/week), or smoker(cigarette>10cigarettes /day)
10. Subject takes ethical drug or herbal medicine within 14days, OTC within 7days before the beginning of study treatment but investigator determine that the taking drug affect this study or could affect the safety of the subjects.
11. Subject who takes inhibitors and inducers of drug metabolizing enzyme(Barbiturates etc.) within 30 days.
12. Taking foods containing grapefruit within 7 days before the beginning of study treatment(ex. Drinking containing grapefruit of 1L per a day or more within 7 days before the beginning of study treatment)
13. Subject who treated with any investigational drugs within 60days before the beginning of study treatment (However, biologicals applies for 90 days, but can be based on a more extended period of time by considering the half-life.
14. Previously donate whole blood within 60 days or component blood within 30days.
15. An impossible one who participants in clinical trial by investigator's decision including laboratory test result or another reason.
16. Positive for Hepatitis B, Hepatitis C, HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg	Drug: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg; 3 Tablets (telmisartan 80mg, amlodipine 5mg, atorvastatin 40mg each one),; oral intake, once in a period; over the period Ⅰ&Ⅱ(crossover); Drug: atorvastatin 40mg; 1 Tablet (atorvastatin 40mg),; oral intake, once in a period; over the period Ⅰ&Ⅱ(crossover)
ACTIVE_COMPARATOR: Atorvastatin 40mg	Drug: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg; 3 Tablets (telmisartan 80mg, amlodipine 5mg, atorvastatin 40mg each one),; oral intake, once in a period; over the period Ⅰ&Ⅱ(crossover); Drug: atorvastatin 40mg; 1 Tablet (atorvastatin 40mg),; oral intake, once in a period; over the period Ⅰ&Ⅱ(crossover)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In the steady state atorvastatin 40mg AUClast	AUClast: Area under the plasma concentration time curve from zero time until the last measurable concentration.	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state atorvastatin 40mg Cmax	Cmax: maximum plasma drug concentration	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In the steady state atorvastatin 40mg AUCinf	AUCinf: Area Under the Concentration time curve from time zero to infinity	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state atorvastatin 40mg Tmax	Tmax: Time to Cmax	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state atorvastatin 40mg t1/2	t1/2: Observed terminal elimination half-life	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
Number of participants with adverse events	Evaluated safety parameters included: physical examination, vital sign, laboratory test, ECG; Adverse event monitoring	From 1day to 17days
In the steady state Orthohydroxy-atorvastatin AUClast	AUClast: Area under the plasma concentration time curve from zero time until the last measurable concentration.	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state Orthohydroxy-atorvastatin Cmax	Cmax: maximum plasma drug concentration	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state Orthohydroxy-atorvastatin AUCinf	AUCinf: Area Under the Concentration time curve from time zero to infinity	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state Orthohydroxy-atorvastatin Tmax	Tmax: Time to Cmax	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose
In the steady state Orthohydroxy-atorvastatin t1/2	t1/2: Observed terminal elimination half-life	0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48hr post-dose

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): May 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: April 25, 2013
• First Submitted That Met QC Criteria: April 26, 2013
• First Posted (ESTIMATE): April 29, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 1, 2013
• Last Update Submitted That Met QC Criteria: July 31, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Healthy volunteers; Atorvastatin; Pharmacokinetic; Telminouveau
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hypertension; Essential Hypertension; Hyperlipidemias; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Atorvastatin; Amlodipine; Telmisartan
• Other Study ID Numbers: 142HPS13002