Estriol and Trimegestone Dose-response Trial With Single Dose Application of Vaginal Rings

NCT ID: NCT03343912

Last Updated: 2020-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-10
• Study Completion Date: 2018-02-15

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.

Conditions

Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Estriol 0.400 mg/day and Trimegestone 0.06 mg/day

Intervention Type: DRUG

Vaginal ring with a nominal delivery rate of 0.400 mg/d estriol (E3) and 0.06 mg/d trimegestone (TMG), vaginal application

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

Group Type: EXPERIMENTAL

Estriol 0.300 mg/day and Trimegestone 0.12 mg/day

Intervention Type: DRUG

Vaginal ring with a nominal delivery rate of 0.300 mg/d estriol (E3) and 0.12 mg/d trimegestone (TMG), vaginal application

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

Group Type: EXPERIMENTAL

Estriol 0.200 mg/day and Trimegestone 0.18 mg/day

Intervention Type: DRUG

Vaginal ring with a nominal delivery rate of 0.200 mg/d estriol (E3) and 0.18 mg/d trimegestone (TMG), vaginal application

Interventions

Estriol 0.400 mg/day and Trimegestone 0.06 mg/day

Vaginal ring with a nominal delivery rate of 0.400 mg/d estriol (E3) and 0.06 mg/d trimegestone (TMG), vaginal application

Intervention Type: DRUG

Estriol 0.300 mg/day and Trimegestone 0.12 mg/day

Vaginal ring with a nominal delivery rate of 0.300 mg/d estriol (E3) and 0.12 mg/d trimegestone (TMG), vaginal application

Intervention Type: DRUG

Estriol 0.200 mg/day and Trimegestone 0.18 mg/day

Vaginal ring with a nominal delivery rate of 0.200 mg/d estriol (E3) and 0.18 mg/d trimegestone (TMG), vaginal application

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

SocraTec R&D GmbH

OTHER

Sponsor Role: collaborator

Galeno Desenvolvimento de Pesquisas Clínicas

OTHER_GOV

Sponsor Role: lead

Responsible Party

Gilberto De Nucci

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gilberto De Nucci, MD

Role: PRINCIPAL_INVESTIGATOR

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

Locations

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

Campinas, São Paulo, Brazil

Countries

Brazil

Other Identifiers

GDN 012/17

Identifier Type: -

Identifier Source: org_study_id