Bioavailability of Clormadinone/Ethinyl Estradiol Tablets 2 mg/0.02 mg With Regards to Reference Product

Laboratorios Andromaco

Status and phase

Completed

Phase 1

Conditions

Bioequivalence

Treatments

Drug: Clormadinone 2 mg and Ethinyl estradiol 0.02 mg Test Product Coated Tablets

Drug: Clormadinone 2 mg and Ethinyl estradiol 0.02 mg Reference Product Coated Tablets

Study type

Interventional

Funder types

Industry

Identifiers

NCT04713904

HP8822-01

Details and patient eligibility

About

The study will be performed at a single site with 38 subjects. Participantswill 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.

Full description

The primary objective of the study is to investigate the relative bioavailability of Clornadinone and Ethinyl estradiol of 2 tablet formulations with Clormadinone 2 mg and Ethinyl estradiol 0.02 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: Evafem 20 [Trademark], product of Grünenthal. 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 Clormadinone 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 postdose. 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 Clormadinone and Ethinyl estradiol in plasma.

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

Enrollment

38 patients

Sex

Female

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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 pharmacological therapy (except over the counter medication use 7 days prior the study)
Hypersensitivity to the study drug or other related compounds, history of serious adverse reactions or hypersensitivity to any medication
Use, during 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 food containing xanthine 24 hours prior each administration of study medication until the last sample of each period
History of any significant cardiovascular disease
Acute disease that generates significant physiological changes from the start of the selection until the end of the study
HIV, Hepatitis B and/or C positive
Presence or history of thrombophlebitis, thrombosis or thromboembolic disorder, deep vein thrombosis, pulmonary embolism or known coagulopathy.
Donation or loss of a significant volume (more tan 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