Clinical trial NCT04193852: Bioavailability of Dienogest and Ethinyl Estradiol Tablets 2.0 mg/0.03 mg With Regards to Reference Product
Official title: Bioavailability of a Formulation of Dienogest and Ethinyl Estradiol 2.0 mg/0.03 mg Coated Tablets With Regards to the Marketed Reference Product
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioequivalence
Lead sponsor: Laboratorios Andromaco S.A.
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This Pilot study will investigate the bioavailability in fasting women of 2 tablet formulations containing Dienogest 2.0 mg and Ethinyl estradiol 0.03 mg.

The Pilot study will be performed at a single site with 10 subjects. Participants will take 2 tablets of the test product and reference product in 2 periods and 2 sequences (either test after reference or reference after test). There will be a washout of at least 14 days between each study period.

Detailed description: The primary objective of the study is to investigate the relative bioavailability of Dienogest and Ethinyl estradiol of 2 tablet formulations with Dienogest 2.0 mg and Ethinyl estradiol 0.03 mg and to demonstrate bioequivalence of both formulations in terms of rate and extent of absorption:

* Test Product: Product manufactured by Laboratorios Andrómaco S.A.
* Reference Product: Valette \[Trademark\], product of Jenapharm, Germany.

The 90% confidence intervals for the intra-subject coefficient of variation (Test versus Reference Product) for the main pharmacokinetic parameters area under the plasma concentration-time curve from time zero to time t (AUC0-t) and from time zero to 72 hours (AUC0-72), and maximum plasma concentration (Cmax) for total Dienogest and Ethinyl estradiol will be determined.

Participants will be confined in the study site for approximately 36 hours during each study period (for 12 hours pre-dosing and for 24 hours post dosing) during which pharmacokinetic (PK) blood samples will be obtained. 16 blood samples will be taken up to 24 hours after the administration in each period. Participants will return to the site to provide additional blood samples at 48 h, and 72 h post-dose.

The washout period between the two study periods will be at least 14 days. The samples from each participant will be analyzed with 2 methods of high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays to quantify total Dienogest and Ethinyl estradiol in plasma.

The safety objective is to evaluate the tolerability of both formulations in women by collecting adverse events.

Eligibility criteria: Inclusion Criteria:

* Non-pregnant and non-breastfeeding women
* Women of childbearing age with an acceptable form of contraception during the study
* 18 to 55 years old inclusive; BMI greater than or equal to 18.51 and less than or equal to 29.99
* Non-smoking or smoke only 3 cigarettes every 7 days
* With results of laboratory tests, electrocardiogram and chest radiography in normal and / or negative or abnormal ranges but without clinical relevance and declared suitable for study by the doctor after the physical examination
* Capable to understand the Informed Consent Form

Exclusion Criteria:

* Study site staff or family members
* With history of drug and/or alcohol abuse
* Smokers more tan 3 cigarettes every 7 days
* Vitamin supplements intake 7 days prior to the administration of the medications under study
* Any recent change in eating habits or physical exercise
* Using of a pharmacological therapy (except over the counter medication use 7 days prior to the study)
* Hypersensitivity to the study drug or to other chemically related compounds, history of serious adverse reactions or hypersensitivity to any medication
* Use, during the 28 days prior to the start of the study, of medications known to alter liver enzyme activity
* Consumption of beverages or food containing grapefruit or pink grapefruit, within 7 days prior to each administration of the study medication and consumption of alcohol, caffeine or beverages or foods containing xanthines 24 hours before each administration of the study medication until the last sample of each period
* History of any significant cardiovascular disease
* Acute disease that generates significant physiological changes from the time of selection until the end of the study
* HIV, Hepatitis B and/or C positive
* Presence or history of thrombophlebitis, thrombosis or thromboembolic disorders, deep vein thrombosis, pulmonary embolism or known coagulopathy.
* Donation or loss of a significant volume (more than 100 mL) of blood or plasma or platelets during the 3 months prior to the start of the study
* Subjects who have participated in any type of clinical study during the 3 months prior to the start of the study
* History of any gastrointestinal surgery that could affect drug absorption
* Presence of fainting history or fear to blood collection

Primary outcomes:
measure: Total Ethinyl estradiol: area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72) ]
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total Dienogest: area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72)
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total Ethinyl estradiol: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total Dienogest: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total Ethinyl estradiol: Maximum plasma concentration (Cmax)
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total dienogest: Maximum plasma concentration (Cmax)
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total dienogest: Time to achieve maximum plasma concentration (tmax)
timeFrame: From tablet intake and up to 72 hours after tablet intake
measure: Total Ethinyl estradiol: Time to achieve maximum plasma concentration (tmax)
timeFrame: From tablet intake and up to 72 hours after tablet intake
Secondary outcomes:
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Innolab
Study officials:
affiliation: Grünenthal Group
name: Study Director Laboratorios Andromaco
role: STUDY_DIRECTOR
References: