MenopausePhase 1NCT03363997
Pharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days
A Phase 1 study testing Estriol 0.125 mg/day, Estriol 0.250 mg/day and Estriol 0.500 mg/day in people with Menopause, run by Galeno Desenvolvimento de Pesquisas Clínicas at 1 site in Brazil.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause
- What is being tested?
- Estriol 0.125 mg/day, Estriol 0.250 mg/day and Estriol 0.500 mg/day
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteBrazil
- Study dates
- 23 Sep 2016to 6 Jun 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 21Show fewer
- 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
- Blood donation or other blood loss of more than 400 ml within the last 3 months prior to individual enrolment of the subject
- Participation in a clinical trial during the last 6 months prior to individual enrolment of the subject
- Concomitant systemic therapy with antibiotics, which might interfere with enterohepatic recirculation (e.g. cephalosporines, neomycin, ampicillin or tetracyclines)
- Use of sex hormones within 6 months (oral, transdermal, vaginal) or 8 months (intramuscular administered depot preparations used once per month) or 12 months (intramuscular administered depot preparations used once per 3 months) before screening
- Use of systemic or topical medications or substances which oppose the study objectives or which might influence them within 8 weeks before screening examination
- Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
Campinas, São Paulo
About this study
Official title: A Randomized, Open-label Trial to Evaluate the Pharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days in Healthy, Post-menopausal Women
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.
Read the detailed description
This phase I, single center, open-label, randomised (allocation to treatment), balanced, single dose trial was performed in a parallel-group design. The subjects were randomly assigned to one of the 3 possible treatments (single vaginal application of 1 vaginal ring containing 100, 300 or 600 mg estriol, with delivery rate of 0.125, 0.250 or 0.500 mg/day over 21 days.
Blood samples were collected at 0.5 h prior to drug application, 1, 2, 4, 6, 12, 24, 48, 96, 144, 216, 288, 360, 432 h after application; 5 min prior to removal, i.e., 21 d after application (study day 22), as well as 6, 12 and 24 h after removal to characterise pharmacokinetic parameters of estriol in plasma.
Serum concentrations of follicle stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) and gynaecological parameters (cytology of vaginal smear, the maturation index and the vaginal pH) were evaluated as pharmacodynamic parameters.
The safety and tolerability was assessed by endometrial thickness and documentation of adverse events.
- Conditions
- Menopause
- Being tested
- Estriol 0.125 mg/day, Estriol 0.250 mg/day, Estriol 0.500 mg/day
- Keywords
- estriol, pharmacokinetic, pharmacodynamic, hormone replacement therapy, vaginal ring administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estriol 0.125 mg/dayDrug
Application of one vaginal ring
Estriol 0.250 mg/dayDrug
Application of one vaginal ring
Estriol 0.500 mg/dayDrug
Application of one vaginal ring
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Estriol 0.500 mg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of estriol plasma levels
Blood sampling for the determination of plasma levels of estriol in participants of each treatment group.
Measured: 0-22 days
Secondary outcomes (9)
Maximum Plasma Concentration (Cmax) of estriol
Determination of Cmax for estriol based on plasma concentrations of samples obtained.
Measured: 0-22 days
Area Under the Curve (AUC) for estriol
Calculation of the AUC for estriol based on plasma concentrations of samples obtained.
Measured: 0-22 days
Characterisation of follicle stimulating hormone (FSH)
Determination of serum concentrations of FSH under the three treatments
Measured: 0-22 days
Characterisation of luteinising hormone (LH)
Determination of serum concentrations of LH under the three treatments
Measured: 0-22 days
Characterisation of sex hormone binding globulin (SHBG)
Determination of serum concentrations of SHBG under the three treatments
Measured: 0-22 days
Characterisation of cytology of vaginal smear
Characterisation of cytology of vaginal smear (parabasal, intermediate and superficial cells) under the three treatments
Measured: 0-22 days
Calculation of maturation index
Calculation of maturation index under the three treatments
Measured: 0-22 days
Determination of vaginal pH
Determination of vaginal pH under the three treatments
Measured: 0-22 days
Number of adverse events per participant
Number of adverse events, in each treatment group, including clinically relevant alterations of vital signs and laboratory tests results.
Measured: up to 22days after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2017
- Study start23 Sep 2016
- Primary completion15 Dec 2016
- Study completion6 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Galeno Desenvolvimento de Pesquisas Clínicas
- Sponsor type
- Other government
- Collaborators
- SocraTec R&D GmbH
- Responsible party
- Principal investigator, Gilberto De Nucci, Galeno Desenvolvimento de Pesquisas Clínicas
- Investigators
- Gilberto De Nucci, MD, Principal investigator, Galeno Desenvolvimento de Pesquisas Clinicas Ltda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03363997
- Sponsor's protocol ID
- GDN 005/16
- Status last verified
- Nov 2017
- First submitted
- 27 Nov 2017
- Last updated
- 6 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37619252
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Trial to Evaluate the Pharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days in Healthy, Post-menopausal Women
- ClinicalTrials.gov ID
- NCT03363997
- Acronym / sponsor ID
- GDN 005/16
- Conditions
- Menopause
- Keywords
- estriol, pharmacokinetic, pharmacodynamic, hormone replacement therapy, vaginal ring administration
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Galeno Desenvolvimento de Pesquisas ClínicasOther government
- Collaborators
- SocraTec R&D GmbH
- Study start
- 23 Sep 2016 (actual)
- Primary completion
- 15 Dec 2016 (actual)
- Study completion
- 6 Jun 2017 (actual)
- First posted
- 6 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This phase I, single center, open-label, randomised (allocation to treatment), balanced, single dose trial was performed in a parallel-group design. The subjects were randomly assigned to one of the 3 possible treatments (single vaginal application of 1 vaginal ring containing 100, 300 or 600 mg estriol, with delivery rate of 0.125, 0.250 or 0.500 mg/day over 21 days.
Blood samples were collected at 0.5 h prior to drug application, 1, 2, 4, 6, 12, 24, 48, 96, 144, 216, 288, 360, 432 h after application; 5 min prior to removal, i.e., 21 d after application (study day 22), as well as 6, 12 and 24 h after removal to characterise pharmacokinetic parameters of estriol in plasma.
Serum concentrations of follicle stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) and gynaecological parameters (cytology of vaginal smear, the maturation index and the vaginal pH) were evaluated as pharmacodynamic parameters.
The safety and tolerability was assessed by endometrial thickness and documentation of adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Test 1 vaginal ring | Experimental | Drug: Estriol 0.125 mg/daySingle vaginal application of 1 vaginal ring containing 100 mg estriol, with delivery rate of 0.125 mg/day over 21 days |
| Test 2 vaginal ring | Experimental | Drug: Estriol 0.250 mg/daySingle vaginal application of 1 vaginal ring containing 300 mg estriol, with delivery rate of 0.250 mg/day over 21 days |
| Test 3 vaginal ring | Experimental | Drug: Estriol 0.500 mg/daySingle vaginal application of 1 vaginal ring containing 600 mg estriol, with delivery rate of 0.500 mg/day over 21 days |
Who may qualify
- Ages
- 45 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estriol 0.125 mg/dayApplication of one vaginal ring | Drug | Test 1 vaginal ring |
| Estriol 0.250 mg/dayApplication of one vaginal ring | Drug | Test 2 vaginal ring |
| Estriol 0.500 mg/dayApplication of one vaginal ring | Drug | Test 3 vaginal ring |
Primary outcome
Measurement of estriol plasma levels
Time frame: 0-22 days
Blood sampling for the determination of plasma levels of estriol in participants of each treatment group.
9 secondary outcomes
Maximum Plasma Concentration (Cmax) of estriol
Time frame: 0-22 days
Area Under the Curve (AUC) for estriol
Time frame: 0-22 days
Characterisation of follicle stimulating hormone (FSH)
Time frame: 0-22 days
Characterisation of luteinising hormone (LH)
Time frame: 0-22 days
Characterisation of sex hormone binding globulin (SHBG)
Time frame: 0-22 days
Characterisation of cytology of vaginal smear
Time frame: 0-22 days
Calculation of maturation index
Time frame: 0-22 days
Determination of vaginal pH
Time frame: 0-22 days
Number of adverse events per participant
Time frame: up to 22days after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2017.
- Derived from this study: PubMed 37619252Lara 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilberto De Nucci, MD principal investigator
Galeno Desenvolvimento de Pesquisas Clinicas Ltda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Estriol 0.125 mg/day, Estriol 0.250 mg/day and Estriol 0.500 mg/day in people with Menopause, run by Galeno Desenvolvimento de Pesquisas Clínicas at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of estriol plasma levels (time frame: 0-22 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03363997, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2017.