Single Dose Escalation Study to Investigate the Pharmacokinetics as Well as Safety and Tolerability of a Concomitant Administration of Nifedipne GITS and Candesartan Tablets Under Fasting Conditions in Healthy Male Subjects in an Open Label, Non-randomized, Sequential Design.

Study Overview
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Brief Summary
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The objective of the study was to investigate the pharmacokinetics as well as safety and tolerability of a concomitant administration of nifedipine GITS and candesartan tablets under fasting conditions in healthy male subjects.

Detailed Description
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Treatment period 1: Single oral dose of 30 mg nifedipine GITS and 8 mg candesartan as loose combination (Treatment A) Treatment period 2: Single oral dose of 60 mg nifedipine GITS and 16 mg candesartan as loose combination (Treatment B) Treatment period 3: single oral dose of 60 mg nifedipine GITS and 32 mg candesartan as loose combination (Treatment C) Before any study drug administration in each treatment period, subjects were fasted from food for at least 10 hours. Subjects continued fasting until at least 4 hours after study drug administration. The wash-out phase between treatments was 5 days. The blood collection period for pharmacokinetics after administration was 48 h. Afterwards, subjects were discharged from the ward. A safety follow-up visit was performed approximately 7 days after the last administration.

Official Title
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Single Dose Escalation Study to Investigate the Pharmacokinetics as Well as Safety and Tolerability of a Concomitant Administration of Nifedipne GITS and Candesartan Tablets Under Fasting Conditions in Healthy Male Subjects in an Open Label, Non-randomized, Sequential Design.

Conditions
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Clinical Pharmacology

Intervention / Treatment
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* Drug: Nifedipine gastrointestinal therapeutic system (GITS) (Adalat LA, BAY a1040) + Candesartan cilexetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers Age 30-55 years BMI 18.0-29.9 kg/m² Systolic blood pressure (SBP) ≥ 120 and ≤ 145 mmHg

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nifedipine + Candesartan cilexetil<br>Coadministration of single doses of nifedipine and candesartan tablets | Drug: Nifedipine gastrointestinal therapeutic system (GITS) (Adalat LA, BAY a1040) + Candesartan cilexetil<br>* Candesartan and nifedipine were administered together as loose combination with 240 mL non-sparkling water in the morning after a fasting period of at least 10 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall summary of adverse events as a measure of safety and tolarability | Overview of treatment emergent adverse events and drug related adverse events, including information on severity as well as premature termination of study participation due to adverse events. | 7 weeks | 
| Safety related laboratory findings | Laboratory parameters were evaluated in terms of multiples of their upper limits of normal. Changes were considered relevant, if they were at least 1.5 times above the upper limit of normal. | 7 weeks | 
| Pharmacokinetic parameters: Maximum drug concentration in plasma after single dose administration divided by dose (mg) (Cmax/D) |  | 48 hours | 
| Pharmacokinetic parameters: Area under the plasma concentration vs time curve from zero to infinity divided by dose (mg) (AUC/D) |  | 48 hours | 
| Pharmacokinetic parameters: Maximum drug concentration in plasma after single dose administration (Cmax) |  | 48 hours | 
| Pharmacokinetic parameters: Area under the plasma concentration vs time curve from zero to infinity after single (first) dose (AUC) |  | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters: Maximum drug concentration in plasma after single dose administration divided by dose (mg) per kg body weight (Cmax,norm) |  | 48 hours | 
| Pharmacokinetic parameters: Area under the curve divided by dose per kg body weight (AUCnorm) |  | 48 hours | 
| Pharmacokinetic parameters: AUC from time 0 to the last data point (AUC(0-tn)) |  | 48 hours | 
| Pharmacokinetic parameters: Time to reach maximum drug concentration in plasma after single (first) (tmax) |  | 48 hours | 
| Pharmacokinetic parameters: Half-life associated with the terminal slope (t1/2) |  | 48 hours | 
| Pharmacokinetic parameters: Mean residence time (MRT) |  | 48 hours | 
| Pharmacokinetic parameters: Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance) (CL/f) |  | 48 hours |