Characterisation of Relative Bioavailability and Assessment of Bioequivalence of a Newly Developed Ethinylestradiol/Dienogest IR Formulation in Comparison With a Marketed Reference Product (Valette®)
Characterisation of Relative Bioavailability and Assessment of Bioequivalence of a Newly Developed Ethinylestradiol/Dienogest IR Formulation in Comparison With a Marketed Reference Product (Valette®)
The aims of this study were to characterise relative bioavailability of Diena (Test) in comparison to Valette® (Reference) after single dose administration under fasting conditions and to assess bioequivalence of Test vs. Reference after single dose administration under fasting conditions, determined by use of area under the concentration time curve AUC0-tlast and maximal concentration Cmax obtained for ethinylestradiol (EE) and dienogest (DNG). Furthermore, a descriptive characterisation of safety and tolerability of the investigational products in the study population was performed.
Inclusion Criteria:
Exclusion Criteria:
Subjects cannot be included if they match any of the following exclusion criteria:
Safety concerns
existing cardiac or haematological diseases and/or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
existing hepatic and/or renal diseases and/or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
existing gastrointestinal diseases and/or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
pathological ECG (12 standard leads) which might interfere with the safety of the active ingredient
known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations
subjects with severe allergies or multiple drug allergies
systolic blood pressure > 160 mmHg
diastolic blood pressure > 90 mmHg
heart rate < 45 and > 100 bpm
laboratory values out of normal range unless the deviation from normal is judged as not relevant for the study by the investigator
positive anti-HIV-test, HBs-AG-test or anti-HCV-test
presence or history of venous or arterial thrombosis (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction and prodromal conditions (e.g. transient ischaemic attack, angina pectoris)), predisposition for venous or arterial thrombosis (e.g. APC-resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency or other thrombogene coagulopathy, heart valve disorders or thrombogene cardiac dysrhythmias)
presence or history of liver tumours or known or suspected sex-hormone influenced malignancies (e.g. of the breasts or endometrium)
unclarified vaginal bleeding or amenorrhoe
subjects with fructose or galactose intolerance, deficiency of lactase, saccharase-isomaltase or malabsortion of glucose/galactose Lack of suitability for the trial
acute or chronic diseases which could affect absorption or metabolism
history of or current drug or alcohol dependence
regular intake of alcoholic food or beverages of ≥ 20 g per day
subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
regular intake of caffeine containing food or beverages of ≥ 500 mg per day
blood donation or other blood loss of more than 400 ml within the last two months prior to individual enrolment of the subject
participation in a clinical trial during the last two months prior to individual enrolment of the subject
regular treatment with any systemically available medication (except usual replacement therapy with L-thyroxine)
subjects, who report a frequent occurrence of migraine attacks
use of hormonal preparations within 6 weeks (oral, transdermal, vaginal), 2 months (intramuscularly administered depot preparations used once per month) or 6 months (intramuscularly administered depot preparations used once per 3 month) before pre-study examination
For female subjects with childbearing potential only:
positive pregnancy test at pre-study examination
pregnant or lactating women
female subjects who do not agree to apply adequate non-hormonal and highly effective contraceptive methods as defined in Note for Guidance on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals (CPMP/ICH/286/95, modification), November 2000 Administrative reasons
subjects suspected or known not to follow instructions
subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the study The exclusion criteria are chosen to assure that subjects with specific risks for administration of the investigated medicinal products and subjects with conditions, which may have an impact on pharmacokinetic parameters, cannot be included.