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

Recruitment & Eligibility

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

Study & Design

Arm && Interventions

Group	Intervention	Description
Nifedipine/Candesartan (fixed dose)	Nifedipine/Candesartan (BAY 98-7106)	-
Nifedipine/Candesartan (loose)	Nifedipine (Adalat, BAY A1040) and Candesartan (Atacand, BAY 12-9333)	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Recruitment & Eligibility