A Drug Interaction Study of Cilnidipine and Valsartan

Study Overview
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Brief Summary
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The investigators investigate the potential pharmacokinetic drug-drug interaction between Cilnidipine 10 mg and Valsartan 160 mg in healthy male volunteers who receive Cilnidipine 10 mg alone, Valsartan 160 mg , and both together in a 3 period repeatedly.

Detailed Description
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To evaluate the safety, drug-tolerance, pharmacokinetics of Cilnidipine 10 mg or Valsartan 160 mg monotherapy or Cilnidipine 10 mg and Valsartan 160 mg combination in healthy male subjects.

Official Title
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A Randomized, Open-label, Single Dosing, Three-way Crossover Clinical Trial to Investigate the Pharmacokinetic Drug-drug Interaction of Cilnidipine 10 mg and Valsartan 160 mg After Oral Administration in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: C - V - C+V
* Drug: C - C+V - V
* Drug: V - C - C+V
* Drug: V - C+V - C
* Drug: C+V - C - V
* Drug: C+V - V - C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers, age 20 to 40 years The result of Body Mass Index(BMI) is not less than 18.5 kg/m2 , no more than 25 kg/m2 and body weight are least 55 kg Subjects who have no congenital or chronic disease and no abnormal symptom or opinion Acceptable serum test, hematologic test, blood chemistry examination, urin test and ECG, physical examination during screening Subjects who have ability to comprehend the objectives, contents of study and property of study drug before participating in trial and have willingness to sign of informed consent in writing Exclusion Criteria: A subject with clinical evidence or history of hepatic (including carrier of hepatitis virus), renal, respiratory, endocrine, neurologic, immunologic, hematologic, oncologic, psychiatric, or cardiovascular disease A subject with a history of gastrointestinal disease or surgery (except simple appendectomy or repair of hernia), which can influence the absorption of the study drug A subject with history of drug allergies (aspirin, antibiotics, including study drug etc.), or history of clinically significant allergies Systolic blood pressure <100mmHg or Diastolic blood pressure < 60 mmHg, systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100mmHg(Sitting blood pressure) during the screening procedure. Presence or history of drug abuse or positive result in urine drug screening test Use any prescriptive medication, Korean traditional medication not considered acceptable by the clinical investigator during the last 14 days period before first dosing, or use any OTC medication not considered acceptable by the clinical investigator during the last 7 days period before first dosing (if used medication is considered acceptable by investigator, patients can be included) Participation in clinical trials of any drug within 60 days prior to the participation of the study Blood donation during 2 months or apheresis during 1 month before the study Use of alcohol over 21 units/weeks Smoker who smoke more than 20 cigarettes per day A subject who takes grapefruit, grapefruit juice, or grapefruit-containing products within 3 days prior to the participation of the study A subject who takes St John's wort or some food including the ingredient within 14 days prior to the participation of the study Judged to be inappropriate for the study by the investigator after reviewing clinical laboratory results or other reasons.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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: C - V - C+V<br>C - Cilnidipine 10mg will be administered orally only one time. V - Valsartan 160mg will be administered orally only one time. C+V - Cilnidipine 10mg plus Valsartan 160mg will be administered orally only one time | Drug: C - V - C+V<br>* Drug will be administered to according to C - V - C+V sequence for 3 period.<br>|
| Experimental: V - C - C+V<br>C - Cilnidipine 10mg will be administered orally only one time. V - Valsartan 160mg will be administered orally only one time. C+V - Cilnidipine 10mg plus Valsartan 160mg will be administered orally only one time | Drug: V - C - C+V<br>* Drug will be administered to according to V - C - C+V sequence for 3 period.<br>|
| Experimental: V - C+V - C<br>C - Cilnidipine 10mg will be administered orally only one time. V - Valsartan 160mg will be administered orally only one time. C+V - Cilnidipine 10mg plus Valsartan 160mg will be administered orally only one time | Drug: V - C+V - C<br>* Drug will be administered to according to V - C+V - C sequence for 3 period.<br>|
| Experimental: C+V - V - C<br>C - Cilnidipine 10mg will be administered orally only one time. V - Valsartan 160mg will be administered orally only one time. C+V - Cilnidipine 10mg plus Valsartan 160mg will be administered orally only one time | Drug: C+V - C - V<br>* Drug will be administered to according to C+V - C - V sequence for 3 period.<br>|
| Experimental: C+V - C - V<br>C - Cilnidipine 10mg will be administered orally only one time. V - Valsartan 160mg will be administered orally only one time. C+V - Cilnidipine 10mg plus Valsartan 160mg will be administered orally only one time | Drug: C+V - V - C<br>* Drug will be administered to according to C+V - V - C sequence for 3 period.<br>|
| Experimental: C - C+V - V<br>C - Cilnidipine 10mg will be administered orally only one time. V - Valsartan 160mg will be administered orally only one time. C+V - Cilnidipine 10mg plus Valsartan 160mg will be administered orally only one time | Drug: C - C+V - V<br>* Drug will be administered to according to C - C+V - V sequence for 3 period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Cilnidipine 10 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| Cmax of Valsartan 160 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| AUClast of Cilnidipine 10 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| AUClast of Valsartan 160 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of Cilnidipine 10 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| Tmax of Valsartan 160 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| AUCinf of Cilnidipine 10 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| CL/F of Cilnidipine 10 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| AUCinf of Valsartan 160 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 
| CL/F of Valsartan 160 mg |  | 1d(8d, 15d) pre-dose, 0.5, 1, 2, 2.5, 3, 4, 5, 6, 8, 12, 24h post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cilnidipin and valsartn, pharmacokinetic drug drug interaction, oral administration, healthy male subjects