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

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

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

Study Overview

• Status: Completed
• Conditions: Pharmacology, Clinical
• Intervention / Treatment: Drug: Fluconazole (BAYT006267) 150 mg capsules; Drug: Fluconazole 150 mg capsules (DiflucanTM)

Detailed Description

Clinical pharmacology

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluconazole, period 1; 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; Fluconazole 150 mg; Drug: Fluconazole 150 mg capsules (DiflucanTM); Fluconazole 150 mg
Experimental: Fluconazole, period 2; 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; Fluconazole 150 mg; Drug: Fluconazole 150 mg capsules (DiflucanTM); Fluconazole 150 mg

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

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 (Actual): July 31, 2012
• Primary Completion (Actual): September 10, 2012
• Study Completion (Actual): September 10, 2012

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (Actual): April 29, 2019

Study Record Updates

• Last Update Posted (Actual): April 29, 2019
• Last Update Submitted That Met QC Criteria: April 25, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Fluconazole; bioequivalence; capsule
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: 16165; 2011-006159-13 (EudraCT Number)