Study to Investigate the Effect of Atorvastatin on the Pharmacokinetic Properties of Telmisartan/S-amlodipine

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of Atorvastatin on the pharmacokinetic properties of Telmisartan/S-amlodipine

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

Conditions
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Essential Hypertension, Hyperlipidemia

Intervention / Treatment
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* Drug: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg
* Drug: Telmisartan 80mg and S-amlodipine 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 20 aged and 45 aged in healthy male and female Body weight more than 55kg in male, 50kg in female 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 The menopause (there is no natural menses for at least 2 years) Surgical Infertility(hysterectomy or bilateral oophorectomy, tubal ligation or other methods of infertility condition) The male partner infertility before screening (Demonstrated azoospermia after vasectomy)and if this man is the only partner of the female subject. 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) 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: 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. Have a gastrointestinal disease history that can affect drug absorption (Crohn's disease, ulcers, etc.) or surgery (except simple appendectomy or hernia surgery) hypersensitivity reaction to drug or clinically significant hypersensitivity reaction in the history of Investigational drugs (telmisartan, s-amlodipine or atorvastatin calcium) or additives. 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) before 28 days the taking Investigational Products. 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 Sitting SBP > 150 mmHg or < 90 mmHg, Sitting DBP> 100 mmHg or < 50 mmHg , after 5minuts break. Drug abuse or have a history of drug abuse showed a positive for urine drug test. Pregnant or lactating women. A heavy caffeine consumer(caffeine>5cups/day), alcohol consumer(alcohol>210g/week), or smoker(cigarette>10cigarettes/day) 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. Subject who takes inhibitors and inducers of drug metabolizing enzyme(Barbiturates etc.) within 30 days. 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) 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) Previously donate whole blood within 60 days or component blood within 30days. An impossible one who participants in clinical trial by investigator's decision including laboratory test result or another reason. Positive for Serology test(Hepatitis B, Hepatitis C, HIV).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg<br> | Drug: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg<br>* Telmisartan 80mg, S-amlodipine 5mg: 1 tablet, oral, once daily, 1day Atorvastatin 40mg: 1 tablet, oral, once daily, 2days over the period I & II(cross-over)<br>Drug: Telmisartan 80mg and S-amlodipine 5mg<br>* Telmisartan 80mg, S-amlodipine 5mg: 1 tablet, oral, once daily, 1day over the period I & II(cross-over)<br>|
| Active Comparator: Telmisartan 80mg and S-amlodipine 5mg<br> | Drug: Telmisartan 80mg, S-amlodipine 5mg and Atorvastatin 40mg<br>* Telmisartan 80mg, S-amlodipine 5mg: 1 tablet, oral, once daily, 1day Atorvastatin 40mg: 1 tablet, oral, once daily, 2days over the period I & II(cross-over)<br>Drug: Telmisartan 80mg and S-amlodipine 5mg<br>* Telmisartan 80mg, S-amlodipine 5mg: 1 tablet, oral, once daily, 1day over the period I & II(cross-over)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In the steady state Telmisartan 80mg and S-amlodipine 5mg AUClast | AUClast = Area under the plasma concentration-time curve from zero time until the last measurable concentration | Telmisartan: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12, 24, 36, 48hr post-dose, S-amlodipine:Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168hr post-dose | 
| In the steady state Telmisartan 80mg and S-amlodipine 5mg Cmax | Cmax=Maximum Plasma Drug Concentration | Telmisartan: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12, 24, 36, 48hr post-dose, S-amlodipine: Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168hr post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In the steady state Telmisartan 80mg & S-amlodipine 5mg AUCinf | AUCinf=Area under the plasma concentration-time curve from time zero to infinity | Telmisartan: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12, 24, 36, 48hr post-dose, S-amlodipine:Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168hr post-dose | 
| In the steady state Telmisartan 80mg & S-amlodipine 5mg Tmax | Tmax=Time to Cmax | Telmisartan: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12, 24, 36, 48hr post-dose, S-amlodipine:Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168hr post-dose | 
| In the steady state Telmisartan 80mg & S-amlodipine 5mg T1/2 | T1/2=Observed terminal elimination half-life | Telmisartan: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, 12, 24, 36, 48hr post-dose, S-amlodipine:Pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168hr 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 22 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, Telminuvo, Telmisartan, S-amlodipine, Atorvastatin, Healthy volunteers