Comparison of Two Vaginal Tablets, Produced at Different Sites, in Postmenopausal Women With Atrophic Vaginitis

An Open Randomized Two-Way Cross-Over Comparative Bioavailability Study to Compare the Extent of Systemic Absorption of Estradiol After a Single Dose Treatment With Two 25 mcg Estradiol Vaginal Tablet Formulations Administered in Postmenopausal Women With Vaginal Atrophy

This trial is conducted in Europe. The aim of this trial is to compare the absorption of estradiol after a single dose of two 25 mcg estradiol vaginal tablets, produced at two different production sites, in postmenopausal women with atrophic vaginitis.

Study Overview

• Status: Completed
• Conditions: Menopause; Postmenopausal Vaginal Atrophy
• Intervention / Treatment: Drug: estradiol, 25 mcg; Drug: estradiol, 25 mcg

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55127

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects who are able to use the German language, spoken and written
• Postmenopausal women: 5 years or more after last menstruation; or both ovaries surgically removed 2 years or more prior to trial start
• Availability of a normal mammogram within 1 year prior to trial start
• Good general health
• No significant illnesses that could interfere with the subject's participation in the trial, based on the judgment of the physician

Exclusion Criteria:

• Known or suspected allergy to estradiol or related products
• Known, suspected or past history of breast cancer
• Abnormal genital bleeding
• Previous oestrogen and/or progestin hormone replacement therapy
• Use of any type of vaginal or vulvar preparations, e.g. pessaries, contraceptive sponges, douches, vaginal moisturizers, or other non-oestrogenic medications including K-Y jelly etc., 1 month prior to first planned drug administration
• Hot flushes which require systemic hormone replacement treatment
• Known insulin dependent or non-insulin dependent diabetes mellitus
• Systolic blood pressure (BP) of more than 160 mm Hg and/or diastolic BP or more than 100 mm Hg, currently treated or untreated
• Active deep venous thrombosis or thromboembolic disorders or a history of these conditions
• Active arterial thrombosis or a documented history of this condition
• Known or suspected liver and/or kidney impairment based on medical history, physical examination, and/or laboratory results
• Known HIV infection based on laboratory result
• Porphyria
• Body Mass Index (BMI) above 30.0 kg/m2
• Cervical smear presenting PAP of more than class II
• Known or suspected vaginal infection requiring further treatment
• Known alcohol or drug abuse, heavy smoking (more than 20 cigarettes a day)
• Currently using steroid hormones (except topical or inhalation glucocorticoid preparations) and drugs known to significantly influence oestrogen metabolism such as barbiturates, phenytoin, rifampicin, carbamazepine
• Subject who has participated in any other trial involving other investigational products within the last 30 days prior to the first planned drug administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trial part 2	Drug: estradiol, 25 mcg; Single dose of vaginal tablet containing 25 mcg estradiol (Production site A) followed by another single dose of vaginal tablet containing 25 mcg estradiol (Production site B); Drug: estradiol, 25 mcg; Single dose of vaginal tablet containing 25 mcg estradiol (Production site B) followed by another single dose of vaginal tablet containing 25 mcg estradiol (Production site A)
Active Comparator: Trial part 1	Drug: estradiol, 25 mcg; Single dose of vaginal tablet containing 25 mcg estradiol (Production site A) followed by another single dose of vaginal tablet containing 25 mcg estradiol (Production site B); Drug: estradiol, 25 mcg; Single dose of vaginal tablet containing 25 mcg estradiol (Production site B) followed by another single dose of vaginal tablet containing 25 mcg estradiol (Production site A)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the curve (AUC(0-t)), maximal concentration (Cmax) of estradiol after baseline correction	from dosing to day 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events and local tolerability	from dosing to day 4

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: March 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 11, 2010
• First Posted (Estimate): March 12, 2010

Study Record Updates

• Last Update Posted (Estimate): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: VAG-3821; U1111-1113-4908 (Other Identifier: WHO); 2009-017034-50 (EudraCT Number)