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

• ClinicalTrials.gov Identifier: NCT04713904
• Recruitment Status: Completed
• First Posted: January 19, 2021
• Last Update Posted: April 15, 2021
• Sponsor: Laboratorios Andromaco S.A.
• Information provided by (Responsible Party): Laboratorios Andromaco S.A.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bioequivalence	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	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Bioavailability of Formulation Clormadinone/Ethinyl Estradiol Coated Tablets 2 mg/0.02 mg With Regards to the Marketed Reference Product
• Actual Study Start Date: January 16, 2021
• Actual Primary Completion Date: January 16, 2021
• Actual Study Completion Date: February 2, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Clormadinone Ethinyl estradiol Test Product	Drug: Clormadinone 2 mg and Ethinyl estradiol 0.02 mg Test Product Coated Tablets; Investigational Medicinal Product
Active Comparator: Clormadinone Ethinyl estradiol Reference Product	Drug: Clormadinone 2 mg and Ethinyl estradiol 0.02 mg Reference Product Coated Tablets; Evafem 20 (Trademark)

Outcome Measures

Primary Outcome Measures :

1. Total Clormadinone: area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72) ] 21 samples up to 72 hours will be taken after the administration in each period. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]
2. Total Ethinyl estradiol: area under the plasma concentration-time curve from 0 to 72 hours (AUC0-72) ] 21 samples up to 72 hours will be taken after the administration in each period. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]
3. Total Clormadinone: area under the plasma concentration-time curve from 0 to time t (AUC0-t) 21 samples up to 72 hours will be taken after the administration in each period. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]
4. Total Ethinyl estradiol: area under the plasma concentration-time curve from 0 to time t (AUC0-t) 21 samples up to 72 hours will be taken after the administration in each period. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]
5. Total Ethinyl estradiol: Maximum plasma concentration (Cmax) 21 samples up to 72 hours will be taken after the administration in each period. The Cmax will be calculated. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]
6. Total Clormadinone: Maximum plasma concentration (Cmax) 21 samples up to 72 hours will be taken after the administration in each period. The Cmax will be calculated. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]

Secondary Outcome Measures :

1. Total Clormadinone: Time to achieve maximum plasma concentration (tmax) 21 samples up to 72 hours will be taken after the administration in each period. The tmax will be calculated. [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]
2. Total Ethinyl estradiol: Time to achieve maximum plasma concentration (tmax) [ Time Frame: [Time Frame: From tablet intake and up to 72 hours after tablet intake] ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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 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

Contacts and Locations

Locations

Chile

Innolab

Santiago, Chile, 7510491

Sponsors and Collaborators

Laboratorios Andromaco S.A.

More Information

• Responsible Party: Laboratorios Andromaco S.A.
• ClinicalTrials.gov Identifier: NCT04713904
• Other Study ID Numbers: HP8822-01
• First Posted: January 19, 2021
• Last Update Posted: April 15, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Ethinyl Estradiol; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contraceptives, Oral