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Completed

NCT Number: NCT03343912

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

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

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Key information

Conditions

Pregnancy

Age range

18 year–35 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

Campinas, São Paulo, Brazil

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

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

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

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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

  2. 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

  3. 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.

  4. 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

Sponsors and collaborators

Lead sponsor

Galeno Desenvolvimento de Pesquisas Clínicas

Other Gov

Collaborators

  • SocraTec R&D GmbH

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Nov 17, 2017
Registry last updated
May 7, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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