Estriol and Trimegestone Dose-response Trial With Single Dose Application of Vaginal Rings
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.
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
Study Overview
Status
Conditions
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
SP
-
Campinas, SP, Brazil
- Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: Test 1 vaginal ring
Single intravaginal application of 1 vaginal ring of Estriol 0.400 mg/day and Trimegestone 0.06 mg/day (Test 1) over 21 days
|
Vaginal ring with a nominal delivery rate of 0.400 mg/d estriol (E3) and 0.06 mg/d trimegestone (TMG), vaginal application
|
|
EXPERIMENTAL: Test 2 vaginal ring
Single intravaginal application of 1 vaginal ring of Estriol 0.300 mg/day and Trimegestone 0.12 mg/day (Test 2) over 21 days
|
Vaginal ring with a nominal delivery rate of 0.300 mg/d estriol (E3) and 0.12 mg/d trimegestone (TMG), vaginal application
|
|
EXPERIMENTAL: Test 3 vaginal ring
Single intravaginal application of 1 vaginal ring of Estriol 0.200 mg/day and Trimegestone 0.18 mg/day (Test 3) over 21 days
|
Vaginal ring with a nominal delivery rate of 0.200 mg/d estriol (E3) and 0.18 mg/d trimegestone (TMG), vaginal application
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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.
|
0 - 41 days
|
|
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.
|
0 - 23 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Bleeding intensity
Time Frame: start of treatment until 42 days after treatment
|
Bleeding intensity, graded as "no bleeding", "spotting" or "bleeding" as recorded in diary by the subject on a daily basis
|
start of treatment until 42 days after treatment
|
|
Number of adverse events per participant
Time Frame: up to 42 days after treatment
|
Number of adverse events, in each treatment group, including clinically relevant alterations of vital signs and laboratory tests results
|
up to 42 days after treatment
|
|
Maximum Plasma Concentration (Cmax) of E3 and TMG
Time Frame: 0 - 23 days
|
Determination of Cmax for E3 and for TMG, based on plasma concentrations of samples obtained.
|
0 - 23 days
|
|
Area Under the Curve (AUC) for E3 and TMG
Time Frame: 0 - 23 days
|
Calculation of the AUC for E3 and for TMG, based on plasma concentrations of samples obtained
|
0 - 23 days
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Gilberto De Nucci, MD, Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- GDN 012/17
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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