Pivotal Bioequivalence FDC Nifedipine / Candesartan vs. Loose Combination of Single Components, Fed

Study Overview
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Brief Summary
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Randomized, open label, single dose, 2-way crossover study to investigate the bioequivalence of a new fixed dose combination (FDC) tablet of nifedipine GITS and candesartan with the corresponding loose combination under fed conditions.

Detailed Description
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Clinical pharmacology

Official Title
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Single Dose Study to Compare the Pharmacokinetics as Well as Safety and Tolerability of a Novel Fixed Dose Combination of Nifedipine GITS and Candesartan and the Loose Combination of Both Components and to Investigate the Bioequivalence Between the Fixed Dose and the Loose Combination in Healthy Male Subjects Under Fed Conditions in an Open Label, Randomized, 2-way-crossover Design

Conditions
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Hypertension, Essential

Intervention / Treatment
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* Drug: Nifedipine/Candesartan (BAY 98-7106)
* Drug: Nifedipine (Adalat, BAY A1040) and Candesartan (Atacand, BAY 12-9333)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The informed consent form must be signed before any study specific tests or procedures are done Confirmation of the subject's health insurance coverage prior to the first screening visit Healthy male subject Ethnicity: Caucasian Age: 18 to 45 years (inclusive) at the first screening visit Body mass index (BMI) above or equal 18, and below or equal 29.9 kg / m² Ability to understand and follow study-related instructions Exclusion Criteria: Suspicion of drug or alcohol abuse Regular daily consumption of more than 1 L of xanthin-containing beverages Intake of foods or beverages containing grapefruit within 2 weeks prior to the first study drug administration (the same applies to pomelos and St. John's Wort) Use of medication within 4 weeks prior to the first study drug administration which could interfere with the investigational products (e.g. CYP3A inhibitors or CYP3A inducers) examples for CYP3A inhibitors: erythromycin, inhibitors of human HIV protease (e.g. ritonavir, saquinavir), amiodarone, diltiazem, verapamil, fluconazole, itraconazole, ketoconazole, clarithromycin, telithromycin, nefazodon, cimetidine; examples for CYP3A inducers: rifampicin, carbamazepin, phenytoin, phenobarbital, or products containing St. John's Wort; Systolic blood pressure below 116 or above 145 mmHg (after at least 15 min supine) At the first screening visit Diastolic blood pressure above 95 mmHg (after at least 15 min supine) Heart rate below 45 or above 95 beats / min (after at least 15 min supine) at the first screening visit Clinically relevant findings in the physical examination Positive urine drug screening or alcohol breath test Exclusion periods from other studies or simultaneous participation in other clinical studies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nifedipine/Candesartan (fixed dose)<br> | Drug: Nifedipine/Candesartan (BAY 98-7106)<br>* Fixed dose combination of 60 mg nifedipine + 32 mg candesartan (1 tablet in one period)<br>|
| Active Comparator: Nifedipine/Candesartan (loose)<br> | Drug: Nifedipine (Adalat, BAY A1040) and Candesartan (Atacand, BAY 12-9333)<br>* Loose combination of 1 tablet nifedpipine 60mg (Adalat LA) and 2 tablets candesartan 16mg (Atacand) (3 tablets in one period) .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum drug concentration in plasma after dose administration for nifedipine and candesartan | within 48 hours after each dosing | 
| AUC(0-tlast) | Area under the drug-concentration vs. time curve from time 0 to the last data point for nifedipine and candesartan | within 48 hours after each dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the curve from time 0 to infinity after single dose for nifedipine and candesartan | Within 48 hours after each dosing | 
| Cmax,norm | Dose normalized Cmax for nifedipine and candesartan | Within 48 hours after each dosing | 
| AUCnorm | AUC normalized for dose and body weight for nifedipine and candesartan | Within 48 hours after each dosing | 
| AUC(0-48) | Area under the plasma concentration-time curve from time zero to 48h for nifedipine and candesartan | Within 48 hours after each dosing | 
| Tmax | The time of the maximum concentration for nifedipine and candesartan | Within 48 hours after each dosing | 
| t1/2 | Half-life for nifedipine and candesartan | Within 48 hours after each dosing | 
| MRT | The mean residence time for nifedipine and candesartan | Within 48 hours after each dosing | 
| CL/F | Oral plasma clearances for nifedipine and candesartan | Within 48 hours after each dosing | 
| Number of participants with adverse events |  | Approximately 3-7 weeks per subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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essential hypertension, blood pressure, nifedipine, candesartan, FDC