Clinical trial NCT03343912: Estriol and Trimegestone Dose-response Trial With Single Dose Application of Vaginal Rings
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pregnancy
Keywords: Estriol
Trimegestone
Vaginal Ring
Lead sponsor: Galeno Desenvolvimento de Pesquisas Clínicas
Sponsor class: OTHER_GOV
Collaborators: name: SocraTec R&D GmbH
First posted: 2017-11-17
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Measurement of E2 and PG plasma levels
timeFrame: 0 - 41 days
measure: Measurement of E3 and TMG plasma levels
timeFrame: 0 - 23 days
Secondary outcomes:
measure: Bleeding intensity
timeFrame: start of treatment until 42 days after treatment
measure: Number of adverse events per participant
timeFrame: up to 42 days after treatment
measure: Maximum Plasma Concentration (Cmax) of E3 and TMG
timeFrame: 0 - 23 days
measure: Area Under the Curve (AUC) for E3 and TMG
timeFrame: 0 - 23 days
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
state: SP
Study officials:
affiliation: Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
name: Gilberto De Nucci, MD
role: PRINCIPAL_INVESTIGATOR
References: