Bioequivalence Trial to Prove Equal Blood Concentrations of Two Different Fluconazole Formulations

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To compare the bioavailability of a single dose of fluconazole 150 mg capsules (Test product) with the bioavailability of a single dose of Diflucan™ capsules, 150 mg (Reference) administered under fasting conditions in order to assess bioequivalence Secondary Objectives: To assess safety and tolerability in form of adverse events and clinical parameters (systolic/diastolic blood pressure, pulse rate, body temperature, physical examination, electrocardiogram, clinical laboratory testing, and overall tolerability) and to assess further pharmacokinetic parameters of fluconazole

Detailed Description
-----------------
Clinical pharmacology

Official Title
-----------------
An Open-label, Randomized, Two-treatment, Two-period, Two-sequence, Cross-over, Mono-center Bioequivalence Study to Compare Single Doses of Fluconazole 150 mg Capsule (Test Product) With Diflucan™ Capsule 150 mg (Reference) in Healthy Volunteers

Conditions
-----------------
Pharmacology, Clinical

Intervention / Treatment
-----------------
* Drug: Fluconazole (BAYT006267) 150 mg capsules
* Drug: Fluconazole 150 mg capsules (DiflucanTM)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males in the age between 18 and 50 years Subjects with a body weight of at least 50 kg and a BMI between 18.5 and 30.0 kg/m2 Subjects had to be willing to use an acceptable method of contraception (double barrier) during the study and 2 weeks after the end of the study All subjects had to give their written informed consent prior to admission to the trial Legal capacity and subject ability to understand the nature, scope and risk/benefit of the trial Exclusion Criteria: Any finding of physical examination (including blood pressure, pulse rate, and ECG) deviating from normal and of clinical relevance Positive test for hepatitis B surface antigen test, anti hepatitis C virus (anti-HCV), or human immunodeficiency virus (HIV)-1/2 antibodies and HIV-1 p24-antigen Positive drug screen test (verified by Mahsan-Kombi/DOA2 and Kombi 4/O2TSchnelltest), or any history or suspicion of barbiturate, amphetamine, benzodiazepine, cocaine, opiates, and cannabis abuse More than moderate alcohol consumption (>40 g of alcohol regularly per day) Demonstrated excess in xanthine consumption (more than 5 cups of coffee or equivalent per day) Subjects with known hypersensitivity to fluconazole and any other excipient of the test products and subjects with lactose intolerance Subjects with known hypersensitivity to other azoles Any need of medication during the trial except allowed medication (paracetamol up to 1 g a day) Any concomitant medication, including herbal remedies, within 10 days before administration of the investigational medicinal product (IMP), or within a period shorter than 10 times the elimination half-life of the respective medication History of severe allergies, non-allergic drug reactions, multiple drug allergies or active hay fever Any active disease, acute or chronic Febrile or infectious illness within 1 week before screening Any other disease or condition which could influence the metabolism of the drug (e.g., endocrine diseases) Any gastrointestinal complaints within 1 week before screening (gastrointestinal disorders including irritable bowel and gastrointestinal ulcer) Any relevant history of chronic or recurrent metabolic, renal, hepatic, pulmonary, gastrointestinal (especially history of chronic gastritis or peptic ulcers), neurological (especially history of epileptic seizures), endocrinological, immunological, psychiatric or cardiovascular disease, myopathies and bleeding disorders Subjects with QTc intervals of more than 450 ms calculated by Bazett's formula Subjects with a pulse rate below 50 or above 90 beats per minute Subjects with serum creatinine concentrations outside the range of <1.20 mg/dL Subjects with a medical disorder, condition or history of such that could impair the subject's ability to participate or complete this trial in the opinion of the Investigator Participated in the treatment phase of another clinical trial within 30 days prior to first administration of the IMP Blood donation or blood sample collection exceeding 200 mL within the last 30 days Unwilling or unable to comply with all requirements outlined in the protocol Excessive sports or sauna within 5 days before start of the treatment phase Consumption of xanthine- and quinine-containing food and beverages and certain fruit juices such as grapefruit juice within 72 h before IMP administration Alcohol consumption within 24 h before screening and within 72 h before IMP administration (on Day -1 verified by alcohol breath test) History of alcohol or drug abuse within the last 5 years History of smoking (within the last 12 months before screening)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluconazole, period 1<br>Subjects were randomized to receive a single dose of 150 mg fluconazole on Day 1 of period 1 after an overnight fast of at least 10 hours | Drug: Fluconazole (BAYT006267) 150 mg capsules<br>* Fluconazole 150 mg<br>Drug: Fluconazole 150 mg capsules (DiflucanTM)<br>* Fluconazole 150 mg<br>|
| Experimental: Fluconazole, period 2<br>Subjects were randomized to receive a single dose of 150 mg fluconazole on Day 1 of period 2 after an overnight fast of at least 10 hours | Drug: Fluconazole (BAYT006267) 150 mg capsules<br>* Fluconazole 150 mg<br>Drug: Fluconazole 150 mg capsules (DiflucanTM)<br>* Fluconazole 150 mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Concentration maximum | Pre-dose and up to 72 hours post-dose | 
| AUC0-tlast | Area under the plasma concentration time curve from time 0 to the last data point above the lower limit of quantification | Pre-dose and up to 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events as a Measure of safety and tolerability |  | Up to 7 weeks | 
| tmax | Time of maximum concentration | Pre-dose and up to 72 hours post-dose | 
| t½λz | Half-life associated with the terminal slope | Pre-dose and up to 72 hours post-dose | 
| MRT | Mean residence time | Pre-dose and up to 72 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fluconazole, bioequivalence, capsule