Bioavailability Study With Oral Single Dose Administration of Ethinylestradiol and Dienogest

Sponsor

Pharbil Waltrop GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT01600274

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

19.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Characterisation of relative bioavailability of Diena (Test) in comparison to Valette® (Reference) after single dose administration under fasting conditions
Assessment of 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 maximum concentration Cmax obtained for ethinylestradiol (EE) and dienogest (DNG)
Descriptive characterisation of safety and tolerability of the investigational products in the study population

Condition or Disease	Intervention/Treatment	Phase
Focus: Bioequivalence	Drug: Dienogest-Ethinyl Estradiol (test product) Drug: Dienogest-Ethinyl Estradiol (reference product)	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Characterisation of Relative Bioavailability and Assessment of Bioequivalence of a Newly Developed Ethinylestradiol/Dienogest IR Formulation in Comparison With a Marketed Reference Product (Valette®)

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diena Dienogest-Ethinyl Estradiol (test product) tablet	Drug: Dienogest-Ethinyl Estradiol (test product) One tablet of Test Other Names: Diena
Active Comparator: Valette® Dienogest-Ethinyl Estradiol (reference product) tablet	Drug: Dienogest-Ethinyl Estradiol (reference product) One tablet of Reference Other Names: Valette®

Arm

Intervention/Treatment

Experimental: Diena

Dienogest-Ethinyl Estradiol (test product) tablet

Drug: Dienogest-Ethinyl Estradiol (test product)

One tablet of Test

Other Names:

Diena

Active Comparator: Valette®

Dienogest-Ethinyl Estradiol (reference product) tablet

Drug: Dienogest-Ethinyl Estradiol (reference product)

One tablet of Reference

Other Names:

Valette®

Outcome Measures

Primary Outcome Measures

Cmax of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a.]
AUC0-tlast of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a.]

Secondary Outcome Measures

Clast of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
AUCexpol% of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
AUC0-∞ of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
Tmax of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
t1/2 of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
tlast of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
λ of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
MRT of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]
Tlag of EE and DNG after each treatment [PK blood sampling will be performed pre-dose (within 1.5 h prior to administration) as well as 0.25, 0.5, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 36, 48 and 60 h p.a]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

sex: female
ethnic origin: Caucasian
age: 18 - 55 years, inclusive
body-mass index (BMI): more than 19 kg/m² and less than 27 kg/m²
good state of health
non-smoker or an ex-smoker for a least 6 months
written informed consent, after having been informed about benefits and potential risks of the trial, as well as details of the insurance taken out to cover the subject's participating in the study

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.