PregnancyPhase 1NCT03343912
Estriol and Trimegestone Dose-response Trial With Single Dose Application of Vaginal Rings
A Phase 1 study testing Estriol 0.400 mg/day and Trimegestone 0.06 mg/day, Estriol 0.300 mg/day and Trimegestone 0.12 mg/day and Estriol 0.200 mg/day and Trimegestone 0.18 mg/day in people with Pregnancy, run by Galeno Desenvolvimento de Pesquisas Clínicas at 1 site in Brazil.
Trial summary
This clinical trial is performed as proof of pharmacological action investigation by demonstration of ovulation inhibition (dose-response study) under treatment with three Test vaginal rings releasing varying doses of estriol (E3) and trimegestone (TMG). Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pregnancy
- What is being tested?
- Estriol 0.400 mg/day and Trimegestone 0.06 mg/day, Estriol 0.300 mg/day and Trimegestone 0.12 mg/day and Estriol 0.200 mg/day and Trimegestone 0.18 mg/day
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteBrazil
- Study dates
- 10 Nov 2017to 15 Feb 2018
- 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 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Under treatment with a commercially available combined oral contraceptive containing 30 µg ethinylestradiol (EE) and 150 µg levonorgestrel (LVN) for the last 3 months prior to enrolment
- Body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m²
- Good state of health
- Non-smoker, ex-smoker for at least 3 months
- Regular menstrual cycle with a length between 21 and 35 days
- Written informed consent, after having been informed about benefits and potential risks of the clinical trial
Who cannot join
- Existing diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the IMPs
- Subjects with severe allergies or multiple drug allergies
- Positive anti human immunodeficiency virus (anti-HIV) test, hepatitis B surface antigen (HBs-AG) test or anti hepatitis C virus (anti-HCV) test
- Presence or history of venous or arterial thrombosis, cerebrovascular accident, or increased risk of thrombosis
- Diabetes mellitus
- Unclarified vaginal bleeding or frequent infections of the urogenital tract
Show all 13Show fewer
- Severe or chronic constipation
- Presence or history of migraine
- Drug or alcohol dependence
- Blood donation or other blood loss of more than 400 ml within the last 3 months
- Participation in a clinical trial during the last 6 months
- Pregnant or lactating women
- Subjects who do not agree to apply a barrier method for contraception
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: Dose-response Study With Three Vaginal Rings With Different Doses of Estriol and Trimegestone: Effect on Progesterone and Estradiol Levels in Healthy Females With Childbearing Potential
This clinical trial is performed as proof of pharmacological action investigation by demonstration of ovulation inhibition (dose-response study) under treatment with three Test vaginal rings releasing varying doses of estriol (E3) and trimegestone (TMG).
Blood samples for determination of estradiol (E2) and progesterone (PG) levels will serve as pharmacodynamic surrogate parameters for characterization of the treatment effect on the endogenous hormones.
Read more
Blood samples for determination of E3 and TMG in plasma will be collected in order to characterize pharmacokinetic parameters.
Additionally, local tolerability characterized by gynecological inspection of the vaginal mucosa prior to and after insertion of the Investigational Medicinal Product (IMPs) is planned to be assessed
Read the detailed description
The IMPs, releasing either 0.400 mg E3 and 0.06 mg TMG, or 0.300 mg E3 and 0.12 mg TMG, or 0.200 mg E3 and 0.18 mg TMG per 24 h, will be applied intravaginally and remain in the vagina for the subsequent 21 days (single dose, 1 treatment cycle). A total of 36 female subjects, 12 per treatment group, are intended to be randomized.
Blood samples for determination of E2 and PG levels will be collected during treatment and until 20 days after removal of the ring. Blood samples for determination of E3 and TMG in plasma will be collected over the treatment period and until 48 h after removal of the ring.
Bleeding intensity will also be documented during treatment and until 20 days after removal of the vaginal ring in a diary to characterize the effects of the different treatments.
- Conditions
- Pregnancy
- Being tested
- Estriol 0.400 mg/day and Trimegestone 0.06 mg/day, Estriol 0.300 mg/day and Trimegestone 0.12 mg/day, Estriol 0.200 mg/day and Trimegestone 0.18 mg/day
- Keywords
- Estriol, Trimegestone, Vaginal Ring
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estriol 0.400 mg/day and Trimegestone 0.06 mg/dayDrug
Vaginal ring with a nominal delivery rate of 0.400 mg/d estriol (E3) and 0.06 mg/d trimegestone (TMG), vaginal application
Estriol 0.300 mg/day and Trimegestone 0.12 mg/dayDrug
Vaginal ring with a nominal delivery rate of 0.300 mg/d estriol (E3) and 0.12 mg/d trimegestone (TMG), vaginal application
Estriol 0.200 mg/day and Trimegestone 0.18 mg/dayDrug
Vaginal ring with a nominal delivery rate of 0.200 mg/d estriol (E3) and 0.18 mg/d trimegestone (TMG), vaginal application
| Study group | Role | What they receive |
|---|---|---|
| Test 1 vaginal ring | Experimental | Single intravaginal application of 1 vaginal ring of Estriol 0.400 mg/day and Trimegestone 0.06 mg/day (Test 1) over 21 days Receives: Drug: Estriol 0.400 mg/day and Trimegestone 0.06 mg/day |
| Test 2 vaginal ring | Experimental | Single intravaginal application of 1 vaginal ring of Estriol 0.300 mg/day and Trimegestone 0.12 mg/day (Test 2) over 21 days Receives: Drug: Estriol 0.300 mg/day and Trimegestone 0.12 mg/day |
| Test 3 vaginal ring | Experimental | Single intravaginal application of 1 vaginal ring of Estriol 0.200 mg/day and Trimegestone 0.18 mg/day (Test 3) over 21 days Receives: Drug: Estriol 0.200 mg/day and Trimegestone 0.18 mg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of E2 and PG plasma levels
Blood sampling for the determination of plasma levels of E2 and PG, in participants of each treatment group, as surrogate variables for treatment response.
Measured: 0 - 41 days
Measurement of E3 and TMG plasma levels
Blood sampling for the determination of plasma levels of E3 and TMG, in participants of each treatment group.
Measured: 0 - 23 days
Secondary outcomes (4)
Bleeding intensity
Bleeding intensity, graded as "no bleeding", "spotting" or "bleeding" as recorded in diary by the subject on a daily basis
Measured: start of treatment until 42 days after treatment
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 42 days after treatment
Maximum Plasma Concentration (Cmax) of E3 and TMG
Determination of Cmax for E3 and for TMG, based on plasma concentrations of samples obtained.
Measured: 0 - 23 days
Area Under the Curve (AUC) for E3 and TMG
Calculation of the AUC for E3 and for TMG, based on plasma concentrations of samples obtained
Measured: 0 - 23 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start10 Nov 2017
- Primary completion12 Jan 2018
- Study completion15 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PregnancyStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single centre, open-label, randomized (assignment to treatment group), parallel-group, three-arm single-dose clinical trial with application performed over 1 treatment cycle of 21 days.
- Masking
- None (open label)
- Enrolment
- 36 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. - ME
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03343912
- Sponsor's protocol ID
- GDN 012/17
- Status last verified
- May 2020
- First submitted
- 7 Nov 2017
- Last updated
- 7 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-response Study With Three Vaginal Rings With Different Doses of Estriol and Trimegestone: Effect on Progesterone and Estradiol Levels in Healthy Females With Childbearing Potential
- ClinicalTrials.gov ID
- NCT03343912
- Acronym / sponsor ID
- GDN 012/17
- Conditions
- Pregnancy
- Keywords
- Estriol, Trimegestone, Vaginal Ring
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Galeno Desenvolvimento de Pesquisas ClínicasOther government
- Collaborators
- SocraTec R&D GmbH
- Study start
- 10 Nov 2017 (actual)
- Primary completion
- 12 Jan 2018 (actual)
- Study completion
- 15 Feb 2018 (actual)
- First posted
- 17 Nov 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 is performed as proof of pharmacological action investigation by demonstration of ovulation inhibition (dose-response study) under treatment with three Test vaginal rings releasing varying doses of estriol (E3) and trimegestone (TMG).
Blood samples for determination of estradiol (E2) and progesterone (PG) levels will serve as pharmacodynamic surrogate parameters for characterization of the treatment effect on the endogenous hormones.
Blood samples for determination of E3 and TMG in plasma will be collected in order to characterize pharmacokinetic parameters.
Additionally, local tolerability characterized by gynecological inspection of the vaginal mucosa prior to and after insertion of the Investigational Medicinal Product (IMPs) is planned to be assessed
Detailed description
The IMPs, releasing either 0.400 mg E3 and 0.06 mg TMG, or 0.300 mg E3 and 0.12 mg TMG, or 0.200 mg E3 and 0.18 mg TMG per 24 h, will be applied intravaginally and remain in the vagina for the subsequent 21 days (single dose, 1 treatment cycle). A total of 36 female subjects, 12 per treatment group, are intended to be randomized.
Blood samples for determination of E2 and PG levels will be collected during treatment and until 20 days after removal of the ring. Blood samples for determination of E3 and TMG in plasma will be collected over the treatment period and until 48 h after removal of the ring.
Bleeding intensity will also be documented during treatment and until 20 days after removal of the vaginal ring in a diary to characterize the effects of the different treatments.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Single centre, open-label, randomized (assignment to treatment group), parallel-group, three-arm single-dose clinical trial with application performed over 1 treatment cycle of 21 days.
| Arm | Type | Receives |
|---|---|---|
| Test 1 vaginal ring | Experimental | Drug: Estriol 0.400 mg/day and Trimegestone 0.06 mg/daySingle intravaginal application of 1 vaginal ring of Estriol 0.400 mg/day and Trimegestone 0.06 mg/day (Test 1) over 21 days |
| Test 2 vaginal ring | Experimental | Drug: Estriol 0.300 mg/day and Trimegestone 0.12 mg/daySingle intravaginal application of 1 vaginal ring of Estriol 0.300 mg/day and Trimegestone 0.12 mg/day (Test 2) over 21 days |
| Test 3 vaginal ring | Experimental | Drug: Estriol 0.200 mg/day and Trimegestone 0.18 mg/daySingle intravaginal application of 1 vaginal ring of Estriol 0.200 mg/day and Trimegestone 0.18 mg/day (Test 3) over 21 days |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Under treatment with a commercially available combined oral contraceptive containing 30 µg ethinylestradiol (EE) and 150 µg levonorgestrel (LVN) for the last 3 months prior to enrolment
- Body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m²
- Good state of health
- Non-smoker, ex-smoker for at least 3 months
- Regular menstrual cycle with a length between 21 and 35 days
Key exclusion criteria (13 listed)
- Existing diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the IMPs
- Subjects with severe allergies or multiple drug allergies
- Positive anti human immunodeficiency virus (anti-HIV) test, hepatitis B surface antigen (HBs-AG) test or anti hepatitis C virus (anti-HCV) test
- Presence or history of venous or arterial thrombosis, cerebrovascular accident, or increased risk of thrombosis
- Diabetes mellitus
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 0.400 mg/day and Trimegestone 0.06 mg/dayVaginal ring with a nominal delivery rate of 0.400 mg/d estriol (E3) and 0.06 mg/d trimegestone (TMG), vaginal application | Drug | Test 1 vaginal ring |
| Estriol 0.300 mg/day and Trimegestone 0.12 mg/dayVaginal ring with a nominal delivery rate of 0.300 mg/d estriol (E3) and 0.12 mg/d trimegestone (TMG), vaginal application | Drug | Test 2 vaginal ring |
| Estriol 0.200 mg/day and Trimegestone 0.18 mg/dayVaginal ring with a nominal delivery rate of 0.200 mg/d estriol (E3) and 0.18 mg/d trimegestone (TMG), vaginal application | Drug | Test 3 vaginal ring |
Primary outcome
Measurement of E2 and PG plasma levels
Time frame: 0 - 41 days
Blood sampling for the determination of plasma levels of E2 and PG, in participants of each treatment group, as surrogate variables for treatment response.
Measurement of E3 and TMG plasma levels
Time frame: 0 - 23 days
Blood sampling for the determination of plasma levels of E3 and TMG, in participants of each treatment group.
4 secondary outcomes
Bleeding intensity
Time frame: start of treatment until 42 days after treatment
Number of adverse events per participant
Time frame: up to 42 days after treatment
Maximum Plasma Concentration (Cmax) of E3 and TMG
Time frame: 0 - 23 days
Area Under the Curve (AUC) for E3 and TMG
Time frame: 0 - 23 days
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 7 May 2020.
- 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. - ME
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 0.400 mg/day and Trimegestone 0.06 mg/day, Estriol 0.300 mg/day and Trimegestone 0.12 mg/day and Estriol 0.200 mg/day and Trimegestone 0.18 mg/day in people with Pregnancy, 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 13 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 7 May 2020. 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 E2 and PG plasma levels (time frame: 0 - 41 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 May 2020.