A Study to Determine the Bioequivalence of SCH 900068 Compared to Marketed Products (Protocol No. P07551)

Study Overview
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Brief Summary
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The intent of this study is to demonstrate that single doses of the Final Market Image (FMI) ezetimibe/atorvastatin 10mg/10mg and 10mg/80mg fixed dose combination (FDC) tablets are bioequivalent to the same doses of ezetimibe (ZETIA®) and atorvastatin (LIPITOR®) that are coadministered as individual tablets in healthy adults.

Official Title
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A Study to Evaluate the Definitive Bioequivalence of SCH 900068 With Marketed Products (Protocol No. P07551)

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Drug: Ezetimibe
* Drug: Ezetimibe/atorvastatin 10mg/10mg FDC
* Drug: Atorvastatin 10mg
* Drug: Atorvastatin 80mg
* Drug: Ezetimibe/atorvastatin 10mg/80mg FDC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Healthy adult males and females age 18-55 years Body mass index (BMI) between 18-35 kg/m^2 Clinical laboratory tests (complete blood count, blood chemistry, and urinalysis), electrocardiogram, and vital signs must be within normal limits Must agree to refrain from consumption of red wine, grapefruit, and grapefruit-containing products, orange and apple juices, and orange- and apple-containing products from beginning approximately 2 weeks prior to administration of the initial dose of study drug, throughout the study (including the washout interval between treatment periods), and until the poststudy visit Exclusion Criteria Female subjects who are pregnant, intend to become pregnant (within 3 months of ending the study), or are nursing/breastfeeding. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug History of any infectious disease within 4 weeks prior to drug administration Have demonstrated allergic reactions or hypersensitivities or intolerance to atorvastatin or other 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, ezetimibe, or any component/excipient of the study drug or other food, drug, atopic reactions or asthmatic episodes which, in the opinion of the investigator and sponsor, interfere with their ability to participate in the trial. Have a history of prior myopathy or abnormality in liver function studies with statin therapy. Are positive for hepatitis B surface antigen, hepatitis C antibodies, or HIV. Have donated blood in the past 60 days Consume excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day.

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 |
| --- | --- |
| Active Comparator: Ezetimibe 10mg and Atorvastatin 10mg<br>Ezetimibe 10mg tablet and Atorvastatin 10mg tablet coadministered | Drug: Ezetimibe<br>* Ezetimibe 10mg tablet given orally after an overnight fast (at least 10 hours).<br>* Other names: Zetia;Drug: Atorvastatin 10mg<br>* Atorvastatin 10mg given orally after an overnight fast (at least 10 hours).<br>* Other names: Lipitor;|
| Experimental: 10mg Ezetimibe/10mg Atorvastatin<br>10mg Ezetimibe/10mg atorvastatin combination tablet | Drug: Ezetimibe/atorvastatin 10mg/10mg FDC<br>* Ezetimibe/atorvastatin 10mg/10mg FDC tablet given orally after an overnight fast (at least 10 hours).<br>* Other names: SCH 900068;|
| Active Comparator: Ezetimibe 10mg and Atorvastatin 80mg<br>Ezetimibe 10mg tablet and Atorvastatin 80mg tablet coadministered | Drug: Ezetimibe<br>* Ezetimibe 10mg tablet given orally after an overnight fast (at least 10 hours).<br>* Other names: Zetia;Drug: Atorvastatin 80mg<br>* Atorvastatin 80mg tablet given orally after an overnight fast (at least 10 hours).<br>* Other names: Lipitor;|
| Experimental: 10mg Ezetimibe/80mg Atorvastatin<br>Ezetimibe/atorvastatin 10mg/80mg combination tablet | Drug: Ezetimibe/atorvastatin 10mg/80mg FDC<br>* Ezetimibe/atorvastatin 10mg/80mg FDC tablet given orally after an overnight fast (at least 10 hours).<br>* Other names: SCH 900068;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time-curve from time zero to infinity (AUC0-∞) of atorvastatin |  | Hour 0 to Hour 48 | 
| Maximum plasma concentration (Cmax) of atorvastatin |  | Hour 0 to Hour 48 | 
| Area under the concentration time-curves from time zero to the time of last measured concentration (AUC0-last) of unconjugated ezetimibe (EZ) |  | Hour 0 to Hour 96 | 
| Maximum plasma concentration (Cmax) of unconjugated ezetimibe (EZ) |  | Hour 0 to Hour 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperlipidemia, statin, Ezetimibe, Zetia, Atorvastatin, Lipitor