Single intravaginal application of 1 vaginal ring of Estriol 0.400 mg/day and Trimegestone 0.06 mg/day (Test 1) over 21 days

Single intravaginal application of 1 vaginal ring of Estriol 0.300 mg/day and Trimegestone 0.12 mg/day (Test 2) over 21 days

Single intravaginal application of 1 vaginal ring of Estriol 0.200 mg/day and Trimegestone 0.18 mg/day (Test 3) over 21 days

Pregnancy

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

Estriol 0.400 mg/day and Trimegestone 0.06 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

Estriol 0.300 mg/day and Trimegestone 0.12 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

Estriol 0.200 mg/day and Trimegestone 0.18 mg/day

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

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

Blood sampling for the determination of plasma levels of E2 and PG, in participants of each treatment group, as surrogate variables for treatment response.

Blood sampling for the determination of plasma levels of E3 and TMG, in participants of each treatment group.

Bleeding intensity, graded as "no bleeding", "spotting" or "bleeding" as recorded in diary by the subject on a daily basis

Number of adverse events, in each treatment group, including clinically relevant alterations of vital signs and laboratory tests results

Determination of Cmax for E3 and for TMG, based on plasma concentrations of samples obtained.

Calculation of the AUC for E3 and for TMG, based on plasma concentrations of samples obtained

Gilberto De Nucci

Director

Galeno Desenvolvimento de Pesquisas Clínicas

SocraTec R&D GmbH

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.

Bevacizumab: 1% solution in saline, 0.1 ml spray in each nostril bid

Bevacizumab Spray

Estriol: 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid

Estriol Spray

Tranexamic Acid: 10% solution in saline, 0.1 ml spray in each nostril bid

Tranexamic Acid Spray

Sterile saline: 0.9%, 0.1 ml spray in each nostril bid

Placebo Spray

Total

Sex: Female, Male

Race (NIH/OMB)

Definite HHT

Epistaxis history

Epistaxis severity score

Frequency of Epistaxis

Duration of Epistaxis

Hoag Epistaxis Severity Score (ESS) is based on 6 nosebleed variables such as frequency and duration which are entered by patients. The ESS has a minimum value of 0 and maximum value of 10, with 10 representing more severe epistaxis.

Hoag Epistaxis Severity Score

Hemoglobin Level

Number of participants requiring RBC transfusion during weeks 1-12

Number of Participants Requiring Red Blood Cell (RBC) Transfusion

Treatment failure is defined as the occurrence of one or more of the following during the study: need for nasal surgery or chemical cautery or other new treatment modality to control epistaxis; transfusion of more than 12 units of RBC; severe complications such as acute myocardial infarction, venous thromboembolism, brain hemorrhage; or death

Number of Participants With Treatment Failure

Treatment Phase (on Drug)

Observation Phase (Off Drug)

James R. Gossage, MD, Medical Director of Cure HHT

Telangiectasia, Hereditary Hemorrhagic

Epistaxis

Sterile saline

1% solution in saline, 0.1 ml spray in each nostril bid

Bevacizumab

0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid

Estriol

10% solution in saline, 0.1 ml spray in each nostril bid

estriol/kraujavimas

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

North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)

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