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

NCT03343912 | Completed Phase 1

• 1 other identifier: GDN 012/17
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Conditions

Pregnancy

Keywords

Estriol; Trimegestone; Vaginal Ring

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  0 - 23 days

Secondary Outcomes (4)

• Bleeding intensity

  start of treatment until 42 days after treatment

• Number of adverse events per participant

  up to 42 days after treatment

• Maximum Plasma Concentration (Cmax) of E3 and TMG

  0 - 23 days

• Area Under the Curve (AUC) for E3 and TMG

  0 - 23 days

Study Arms (3)

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

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

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

Drug: Estriol 0.200 mg/day and Trimegestone 0.18 mg/day

Interventions

Estriol 0.400 mg/day and Trimegestone 0.06 mg/day 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 1 vaginal ring

Estriol 0.300 mg/day and Trimegestone 0.12 mg/day 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 2 vaginal ring

Estriol 0.200 mg/day and Trimegestone 0.18 mg/day DRUG

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

Test 3 vaginal ring

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Galeno Desenvolvimento de Pesquisas Clínicas: lead
• SocraTec R&D GmbH: collaborator

Study Sites (1)

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

Campinas, São Paulo, Brazil

Location

MeSH Terms

Interventions

Estriol; trimegestone

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Gilberto De Nucci, MD

  Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Model Details: 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.

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 17, 2017
• Study Start: November 10, 2017
• Primary Completion: January 12, 2018
• Study Completion: February 15, 2018
• Last Updated: May 7, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)