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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Menopause
• Intervention / Treatment: Drug: 2 mg estradiol / 1 mg norethisterone acetate (NETA)

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany, 89231

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: New formulation	Drug: 2 mg estradiol / 1 mg norethisterone acetate (NETA); 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.
Active Comparator: Old formulation	Drug: 2 mg estradiol / 1 mg norethisterone acetate (NETA); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: May 9, 2012
• First Submitted That Met QC Criteria: May 9, 2012
• First Posted (Estimate): May 10, 2012

Study Record Updates

• Last Update Posted (Estimate): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Estradiol; Norethindrone; Norethindrone Acetate
• Other Study ID Numbers: KLI-1915; 2007-003350-28 (EudraCT Number)