Investigation of 2 Different Oral Formulations of Estradiol and Norethisterone in Healthy Women

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to investigate whether a reformulated estradiol/norethisterone acetate (NETA) formulation is bioequivalent to that of Kliogest® (estradiol/norethisterone acetate (NETA) in healthy women.

Official Title
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Single Dose, Double-blind, Two-way Cross-over Bioequivalence Trial With 2 Different Oral Formulations of Estradiol and Norethisterone

Conditions
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Menopause, Healthy

Intervention / Treatment
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* Drug: 2 mg estradiol / 1 mg norethisterone acetate (NETA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal defined as at least 12 months spontaneous amenorrhoea, with serum FSH (follicle stimulating hormone) levels at least 40 IU/L and estradiol maximum 25 pg/mL. If the date of spontaneous amenorrhoea can not be identified because of previous hormone replacement therapy, serum FSH at least 40 IU/L and estradiol maximum 25 pg/mL Non-smoking Body Mass Index (BMI) maximum 35.0 kg/m^2 Able to understand, read and speak German fluently Good state of health evidenced by medical history, physical examination including gynecological examination, and results from laboratory examination Willing to abstain from intake of caffeine containing food and beverages within 48 hours before drug administration Exclusion Criteria: Known or suspected allergy to trial products or related products Previous use of oral, transdermal, nasal spray, vaginal preparations and implants within 8 weeks prior to the planned first drug administration Known, suspected or history of breast cancer Known or suspected estrogen dependent neoplasia e.g. endometrial cancer Abnormal genital bleeding of unknown aetiology Known insulin dependent as well as non-insulin dependent diabetes mellitus Positive test for HIV (human immunodeficiency virus) and/or hepatitis B and C Systolic blood pressure (BP) above or equal to 160 mm Hg and/or diastolic BP above or equal to 100 mm Hg, currently treated or untreated

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: New formulation<br> | Drug: 2 mg estradiol / 1 mg norethisterone acetate (NETA)<br>* A single dose of one tablet under fasting conditions separated by a wash-out period of 2 weeks (+0-2 days) between dosing visits. Administered orally.<br>|
| Active Comparator: Old formulation<br> | Drug: 2 mg estradiol / 1 mg norethisterone acetate (NETA)<br>* A single dose of one tablet under fasting conditions separated by a wash-out period of 2 weeks (+0-2 days) between dosing visits. Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Curve (0-t) |  | Up to 72 hours after trial product administration | 
| Cmax, maximum concentration |  | Up to 72 hours after trial product administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum (tmax) |  | Up to 72 hours after trial product administration | 
| Area under the curve from time zero to infinity |  | Up to 72 hours after trial product administration | 
| Terminal half-life (t½) |  | Up to 72 hours after trial product administration | 
| Terminal rate constant |  | Up to 72 hours after trial product administration | 
| Incidence of adverse events (AEs) |  | Week 8 |