Pharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days

NCT03363997 | Completed Phase 1

• 1 other identifier: GDN 005/16
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial evaluated the pharmacokinetics and pharmacodynamics of estriol in healthy post-menopausal women after the application of one vaginal ring containing one of three different dosages of estriol (100 mg (Test 1), 300 mg (Test 2) or 600 mg (Test 3)) with continuous delivery (0.125, 0.250 or 0.500 mg/day) for 21 days. And also, characterized its safety and tolerability.

Conditions

Menopause

Keywords

estriol; pharmacokinetic; pharmacodynamic; hormone replacement therapy; vaginal ring administration

Outcome Measures

Primary Outcomes (1)

• Measurement of estriol plasma levels

  Blood sampling for the determination of plasma levels of estriol in participants of each treatment group.

  0-22 days

Secondary Outcomes (9)

• Maximum Plasma Concentration (Cmax) of estriol

  0-22 days

• Area Under the Curve (AUC) for estriol

  0-22 days

• Characterisation of follicle stimulating hormone (FSH)

  0-22 days

• Characterisation of luteinising hormone (LH)

  0-22 days

• Characterisation of sex hormone binding globulin (SHBG)

  0-22 days

Study Arms (3)

Test 1 vaginal ring

EXPERIMENTAL

Single vaginal application of 1 vaginal ring containing 100 mg estriol, with delivery rate of 0.125 mg/day over 21 days

Drug: Estriol 0.125 mg/day

Test 2 vaginal ring

EXPERIMENTAL

Single vaginal application of 1 vaginal ring containing 300 mg estriol, with delivery rate of 0.250 mg/day over 21 days

Drug: Estriol 0.250 mg/day

Test 3 vaginal ring

EXPERIMENTAL

Single vaginal application of 1 vaginal ring containing 600 mg estriol, with delivery rate of 0.500 mg/day over 21 days

Drug: Estriol 0.500 mg/day

Interventions

Estriol 0.125 mg/day DRUG

Application of one vaginal ring

Test 1 vaginal ring

Estriol 0.250 mg/day DRUG

Application of one vaginal ring

Test 2 vaginal ring

Estriol 0.500 mg/day DRUG

Application of one vaginal ring

Test 3 vaginal ring

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body-mass index (BMI) ≥18.5 kg/m² and ≤ 30.0 kg/m²
• Postmenopausal state: FSH (plasma) ≥ 40 IU/l, estradiol (serum) ≤ 20 pg/ml last spontaneous menstruation at least 12 months ago
• Normal transvaginal endometrial scan (endometrial thickness \< 5 mm)
• Good state of health
• Non-smoker or ex-smoker for at least 6 month
• Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial

You may not qualify if:

• Existing cardiac, hepatic and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability and/or pharmacokinetics and/or pharmacodynamics of the active ingredient
• History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
• Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations
• Subjects with severe allergies or multiple drug allergies, unless it is judged as not relevant for the clinical trial by the investigator
• Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCV-test
• Presence or history of venous or arterial thrombosis (e.g. deep venous thrombosis, pulmonary embolism)
• Known, past or suspected breast cancer or increased familiar risk for development
• Known or suspected estrogen-dependent malignant tumours (e.g. endometrial or breast cancer)
• Undiagnosed genital bleeding
• Acute vaginal infection or other diseases prohibiting the placement of vaginal ring
• History of endometrial hyperplasia
• Migraine or frequent episodes of severe headache
• History of or current drug or alcohol dependence
• Subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
• Regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day

Sponsors & Collaborators

• Galeno Desenvolvimento de Pesquisas Clínicas: lead
• SocraTec R&D GmbH: collaborator

Study Sites (1)

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

Campinas, São Paulo, Brazil

Location

Related Publications (1)

• Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-E-Silva ACJ, Ferriani RA, Martins WP, Fuentealba-Torres M. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2023 Aug 24;8(8):CD009672. doi: 10.1002/14651858.CD009672.pub3.

  PMID: 37619252 DERIVED

MeSH Terms

Interventions

Estriol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Gilberto De Nucci, MD

  Galeno Desenvolvimento de Pesquisas Clinicas Ltda

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 6, 2017
• Study Start: September 23, 2016
• Primary Completion: December 15, 2016
• Study Completion: June 6, 2017
• Last Updated: December 6, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)