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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension, Essential
• Intervention / Treatment: Drug: Nifedipine/Candesartan (BAY 98-7106); Drug: Nifedipine (Adalat, BAY A1040) and Candesartan (Atacand, BAY 12-9333)

Detailed Description

Clinical pharmacology

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: April 18, 2011
• First Submitted That Met QC Criteria: May 9, 2011
• First Posted (Estimate): May 10, 2011

Study Record Updates

• Last Update Posted (Estimate): December 10, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: essential hypertension, blood pressure, nifedipine, candesartan, FDC
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Tocolytic Agents; Nifedipine; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: 14028; 2011-000322-29 (EudraCT Number)