Study of no Pharmacokinetic Interaction Between Rosuvastatin 20mg and Ezetimibe10mg, Fixed Dose vs Individual Components

Study Overview
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Brief Summary
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Monocentric study of no pharmacokinetic interaction between rosuvastatin 20 mg and ezetimibe 10 mg. An open design, randomized, single dose with three periods, six sequences and crossed, in healthy volunteers with fasting conditions, managed in fixed dose combination (Sponsor Laboratorios Silanes S.A. de C.V.) versus individual components managed by separated (Crestor®, product of Astrazeneca, S.A. de C.V and Ezetrol®. product of Undra S.A. de C.V.)

Detailed Description
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To statistically compare the bioavailability of rosuvastatin 20 mg and ezetimibe 10 mg in a pharmacokinetic non-interference study, after single-dose oral administration of a product with the fixed combination of active ingredients with respect to the individual components administered separately in healthy volunteers fasting. In the same way, the safety of the presentations will be evaluated based on the registry of adverse events at the end of the three study periods. The classic 90% confidence intervals will be determined for the intra-individual ratios (test / reference) of the main parameters AUC0-t, AUC0-inf, Cmax for rosuvastatin and ezetimibe.

Official Title
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Study of no Pharmacokinetic Interaction Between Rosuvastatin 20 mg and Ezetimibe 10 mg, Open Design, Randomized, Single Dose, 3x6, Crossove, Healthy Volunteers in Fasting, in Fixed Combination Against Individuals Components Managed

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rosuvastatin (20mg) /Ezetimibe (10mg) in fixed dose
* Drug: Rosuvastatin 20mg
* Drug: Ezetimibe 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The body mass index of the subjects should be between 18.0-27.0 according to Quetelet. Women of childbearing age should have a family planning method (including barrier methods, non-hormonal intrauterine devices or bilateral tubal obstruction) or practice abstinence as a lifestyle during the development of the clinical study. Volunteers must be healthy, a criterion determined by the results of a complete medical history carried out by the doctors of the Clinical Research site and the laboratory and cabinet studies carried out in certified Clinical Laboratories. The limits of variation allowed within normality in the selection visit will be: blood pressure (sitting) from 90 to 130 mmHg systolic and 60 to 90 mmHg diastolic, heart rate between 50 and 100 beats per minute and respiratory rate between 14 and 20 breaths per minute according to current SOP with code CLI-DES-008  Measure vital sign. The vital signs will be taken after 5 minutes of rest in the sedent position. The laboratory and office tests that were carried out for the inclusion of the subjects to the study will be: 1. Complete hematic biometry with differential count: Leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean concentration of corpuscular hemoglobin, distribution width of erythrocytes, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils. 2.27-element blood chemistry: glucose, urea, BUN, creatinine, BUN / creatinine ratio, uric acid, cholesterol, HDL cholesterol, triglycerides, LDL cholesterol, non-HDL cholesterol, atherogenic index, total proteins, albumin, globulins, A / ratio G, total bilirubin, direct bilirubin, indirect bilirubin, TGO, TGP, total alkaline phostatase, gamma-glutamyltranspeptidase, DHL, iron, calcium sodium, potassium and chlorine. 3.General urine test. Physical examination (color, appearance, density); chemical test (pH, leukocytes, nitrites, proteins, glucose, ketones, bilirubin, urobilinogen, hemoglobin); microscopic examination (leukocytes, erythrocytes, dysformic erythrocytes, casts, crystals, pavement cells, renal tubular cells, mucoid networks, bacteria and yeasts. 4. Hepatitis B and C test: HBV surface antigen and anti-HCV antibody. 5. HIV test: Anti-HIV 1 and 2 antibodies. 6. VDRL test. 7. Urine drug abuse test at screening visit and approximately 12 hours prior to drug administration. 8. Online alcohol detection test approximately 12 hours prior to drug admission. 9. Serum pregnancy test at screening visit and urine pregnancy test (qualitative) approximately 12 hours before drug administration. 10. 12-lead electrocardiogram (valid for no more than 3 months). Exclusion Criteria: Volunteers with a history of cardiovascular, neurological (uncontrolled seizures), kidney (severe kidney failure), liver (liver failure, active liver disease or increased transaminases that exceed three times the upper limit of normal), pulmonary, muscular (myopathies) ), rhabdomyolysis, hereditary muscle disorders), metabolic, gastrointestinal including constipation, neurological, endpocrine (diabetes mellitus, hypothyroidism), hematopoietic or any type of anemia, mental illness or other organic abnormalities. As well as those who have had a muscle trauma within the 21 days prior to the study. Volunteers who require any medication during the course of the study other than the medication being studied. Volunteers with a history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer. History of hereditary galactose intolerance, Lapp lactase deficiency, or glucose or galactose malabsorption. Volunteers who have been exposed to medications known as liver enzyme inducers or inhibitors or who have taken potentially toxic medications within 30 days prior to the start of the study. Volunteers who have received any medications, including vitamins (with or without a prescription) or herbal remedies 30 days (or 7 half-lives) prior to the start of the study. Current or recent use of fibrates, niacin, cyclosporine, and protease inhibitors. History of muscle toxicity with another HMG-CoA inhibitor or fibrates. Volunteers who have been hospitalized for any problem during the six months prior to the start of the study. Subjects allergic to any medicine, food or substance. Subjects who have ingested alcohol and / or carbonated and / or xanthine-containing beverages (coffee, tea, cocoa, chocolate, mate, cola soft drinks) or who have ingested charcoal-grilled food or grapefruit juice within 10 hours prior to the start of the hospitalization period, or subjects who smoked tobacco within 10 hours prior to the start of the study. Subjects who have donated or lost 450 ml or more of blood within the 60 days prior to the start of the study. Subjects with a history of abuse and dependence on alcohol or psychoactive substances. Volunteers requiring a special diet for any reason, for example vegetarian. Incapacity of any kind that makes it impossible for the volunteer to understand the nature, objective and possible consequences of the study. Evidence of uncooperative attitude during the study. Volunteers with positive drug abuse, pregnancy and / or alcohol testing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Group A: Rosuvastatin / Ezetimibe fixed dose<br>In fixed dose Pharmaceutical Form: Tablets Dosage: 20 mg / 10 mg Administration way: oral | Drug: Rosuvastatin (20mg) /Ezetimibe (10mg) in fixed dose<br>* Form: Tablets Dosage: 20 mg Adminstration way: Oral<br>* Other names: ROSU/EZET;|
| Active Comparator: Group B: Rosuvastatin (Crestor®)<br>Pharmaceutical Form: Tablets Dosage: 20 mg Adminstration wat: Oral | Drug: Rosuvastatin 20mg<br>* Pharmaceutical Form: Tablets Dosage: 20 mg Adminstration way: Oral<br>* Other names: ROSU (Crestor®);|
| Active Comparator: Group C: Ezetimibe (Ezetrol®)<br>Pharmaceutical Form: Tablets Dosage: 10 mg Adminstration wat: Oral | Drug: Ezetimibe 10mg<br>* Pharmaceutical Form: Tablets Dosage: 10 mg Adminstration way: Oral<br>* Other names: EZET (Ezetrol®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration following the treatment (Cmax | Evaluate the fixed dose pharmacokinetics profile of rosuvastatin/ezetimibe, employing the maximum observed concentration following the treatment (Cmax) | Baseline, 0.25, 0.50, 0.75, 1.00. 2.00, 3.00, 4.00, 5.00, 6.00. 7.00, 8.00, 10.00, 14.00, 24.00. 36.00, 48.00. 72.00 and 96.00 hours | 
| The area under the curve from time zero to the last measurable concentration (AUC 0-t)using the linear trapezoidal linear-interpolation method | Evaluate the fixed dose pharmacokinetics profile of rosuvastatin/ezetimibe, employing the area under the curve from time zero to the last measurable concentration (AUC 0-t)using the linear trapezoidal linear-interpolation method. | Baseline, 0.25, 0.50, 0.75, 1.00. 2.00, 3.00, 4.00, 5.00, 6.00. 7.00, 8.00, 10.00, 14.00, 24.00. 36.00, 48.00. 72.00 and 96.00 hours | 
| The area under the curve from time zero to infinity calculated (AUC 0-inf), | Evaluate the fixed dose pharmacokinetics profile of rosuvastatin/ezetimibe, employing the area under the curve from time zero to infinity calculated (AUC 0-inf). | Baseline, 0.25, 0.50, 0.75, 1.00. 2.00, 3.00, 4.00, 5.00, 6.00. 7.00, 8.00, 10.00, 14.00, 24.00. 36.00, 48.00. 72.00 and 96.00 hours | 
| Time of the maximum measured concentration (Tmax). | Evaluate the fixed dose pharmacokinetics profile of Rosuvastatin/ezetimibe, employing time of the maximum measured concentration (Tmax). | Baseline, 0.25, 0.50, 0.75, 1.00. 2.00, 3.00, 4.00, 5.00, 6.00. 7.00, 8.00, 10.00, 14.00, 24.00. 36.00, 48.00. 72.00 and 96.00 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sitting blood pressure (mmHg). | The sitting blood pressure was measured and registered at case format report throughout the study. | Prior to dosing, at 02.00, 06.00,14.00, 24.00, 36.00, 48.00, 72.00 and 96.00 hours | 
| Pulse rate (p/m). | The pulse rate was measured and registered at case format report throughout the study. | Prior to dosing, at 02.00, 06.00,14.00, 24.00, 36.00, 48.00, 72.00 and 96.00 hours | 
| Respiratory rate (rr). | The respiratory rate was measured and registered at case format report throughout the study. | Prior to dosing, at 02.00, 06.00,14.00, 24.00, 36.00, 48.00, 72.00 and 96.00 hours | 
| Axillary-body temperature (°C). | The axillary-body temperature was measured and registered at case format report throughout the study. | Prior to dosing, at 02.00, 06.00,14.00, 24.00, 36.00, 48.00, 72.00 and 96.00 hours | 
| Adverse events | Any adverse event were classified by severity, treatment and its relationship with the study drug was evaluated. | 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyslipidemia, Rosuvastatin, Ezetimibe, Cholesterol