Single Dose Bioequivalence Study Comparing Nifedipine/Candesartan FDC (Fixed Dose Combination) With Loose Combination of Nifedipine GITS (Gastro-intestinal Therapeutic System) Plus Candesartan and Single Components Under Fasting Conditions

Study Overview
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Brief Summary
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Randomized, open label, single dose, 4-way crossover study to investigate the bioequivalence of a new fixed dose combination tablet of nifedipine GITS and candesartan with the corresponding loose combination and to compare it with the individual drugs

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, the Loose Combination of Both and the Single Components Alone and to Investigate the Bioequivalence Between the Fixed Dose and the Loose Combination in Healthy Male Volunteers Under Fasting Conditions in an Open Label, Randomized, 4-way-crossover Design

Conditions
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Hypertension, Essential

Intervention / Treatment
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* Drug: Nifedipine-candesartan FDC (BAY 98-7106)
* Drug: Nifedipine GITS (Adalat LA, BAYA1040)
* Drug: Candesartan (Atacand)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subject Age: 18 to 45 years (inclusive) at the first screening / examination visit Ethnicity: Caucasian Body mass index (BMI): >/=18 and </=29,9 kg/m² Exclusion Criteria: Systolic blood pressure below 120 or above 145 mmHg Diastolic blood pressure above 95 mmHg Heart rate below 45 or above 95 beats / min Clinically relevant findings in the physical examination 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 4 weeks before the pre-study examination

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nifedipine-candesartan FDC<br>Each subject received single fixed dose combination of 60 mg nifedipine and 32 mg candesartan orally. | Drug: Nifedipine-candesartan FDC (BAY 98-7106)<br>* Single dose of 1 FDC tablet consisting of 60 mg nifedipine GITS and 32 mg candesartan<br>|
| Active Comparator: Nifedipine and candesartan<br>Each subject received one dose of nifedipine GITS 60 mg and candesartan 32 mg (2 x 16 mg tablet) as loose combination, orally. | Drug: Nifedipine GITS (Adalat LA, BAYA1040)<br>* Single oral dose of 1 tablet of nifedipine GITS 60 mg<br>Drug: Candesartan (Atacand)<br>* Single oral dose of 32 mg (2 x 16 mg tablet) candesartan<br>|
| Active Comparator: Nifedipine<br>Each subject received one dose of nifedipine GITS 60 mg orally. | Drug: Nifedipine GITS (Adalat LA, BAYA1040)<br>* Single oral dose of 1 tablet of nifedipine GITS 60 mg<br>|
| Active Comparator: Candesartan<br>Each subject received one dose of candesartan 32 mg (2 x 16 mg tablet), orally. | Drug: Candesartan (Atacand)<br>* Single oral dose of 32 mg (2 x 16 mg tablet) candesartan<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 treatment | 
| AUC(0-tn) | AUC from time 0 to the last data point for nifedipine and candesartan | Within 48 hours after each treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the plasma concentration vs time curve from zero to infinity after single (first) dose for nifedipine and candesartan | Within 48 hours after each treatment | 
| Cmax,norm | Maximum drug concentration in plasma after dose administration divided by dose (mg) per kg body weight for nifedipine and candesartan | Within 48 hours after each treatment | 
| AUCnorm | Area under the curve divided by dose per kg body weight for nifedipine and candesartan | Within 48 hours after each treatment | 
| AUC(0-48) | AUC from time 0 to time 48 h for nifedipine and candesartan | Within 48 hours after each treatment | 
| tmax | Time to reach maximum drug concentration in plasma after single (first) dose for nifedipine and candesartan | Within 48 hours after each treatment | 
| t½ | Half-life associated with the terminal slope for nifedipine and candesartan | Within 48 hours after each treatment | 
| MRT | Mean residence time for nifedipine and candesartan | Within 48 hours after each treatment | 
| CL/f | Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance) for nifedipine and candesartan | Within 48 hours after each treatment | 
| Number of participants with adverse events |  | Approximately 3.5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Nifedipine, Candesartan, FDC