Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women

Science Valley Research Institute20 enrolled

Overview

A single center, prospective, open-label clinical study will be conducted, to monitor serum concentration and pharmacokinetic profile after subcutaneous implantation of a 25mg-estradiol bioabsorbable implant in postmenopausal women.

Assessing serum total estradiol concentration and determination of pharmacokinetic parameters will be performed in participants eligible for the study before and after the insertion of estradiol pellet (25 mg) at different collection times \[in the first 24 hours, weekly in the first month and monthly until 6 months are complete\]. Additionally, the concentration of other hormones influenced by the action of estradiol will be determined (total testosterone, estrone, FSH, LH, SHBG, and prolactin). Medical visits will be carried out for clinical evaluation and follow-up of the participants in the baseline and after 1 month, 3 months, and 6 months. Assessment of the primary outcome will be performed 6 months after estradiol pellet insertion. N=20 participants.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Climacteric Syndrome Menopause Hypoestrogenism

Interventions

s.c 25 mg estradiol pelletDRUG

Subcutaneous insertion of 25 mg estradiol pellet.

Eligibility

Sex: FEMALEMin age: 41 YearsMax age: 59 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Signed Informed Consent Form * Woman aged ≥ 41 and ≤ 59 years * Weight ≥ 50 kg and ≤ 98 kg * BMI ≥ 18.5 and ≤ 34.9 kg/m² * Hysterectomy (with or without oophorectomy) * Serum total estradiol concentration ≤ 50 pg/mL and serum FSH concentration ≥ 25 mIU/mL, both determined by immunoassays * Presence of menopause-associated symptoms * Absence of signs and symptoms and propedeutics suggestive of breast cancer evidenced by mammography report (woman aged \> 40 years) for less than 12 months = BI-RADS1 or BI-RADS2 * Agreement not to use other hormones (estrogens, androgens and/or progestogens) in any pharmaceutical form during the study Exclusion Criteria: * Contraindications to the use of menopausal hormone therapy: Bleeding vaginal of unknown cause; personal history of hormone-dependent neoplasm including breast cancer, precursor lesions of breast cancer; liver disease; porphyria; personal history of coronary artery disease, cerebrovascular and venous thromboembolism; systemic lupus erythematosus with high thromboembolic risk and meningioma * Comorbidities associated with increased cardiovascular risk: smoking, uncontrolled diabetes, dyslipidemia, and uncontrolled hypertension * Serious chronic disorders, including metastatic malignancies, kidney disease in the end-stage with or without dialysis, clinically unstable heart disease, or any another disorder that, in the opinion of the investigator, excludes the participant from the study * Immunocompromise or suspected or confirmed diagnosis of immunodeficiency based on history and/or physical or laboratory examination * Active liver disease or dysfunction * Benign or malignant tumors of the liver * Clinical diagnosis of polycystic ovary syndrome * Use of other hormones (estrogens, androgens and/or progestogens) in any pharmaceutical form in the last month * Current use of drugs that alter cytochrome P450 and metabolization of Estrogens * Current use of tamoxifen, aromatase inhibitors, or agonists/antagonists GnRH for cancer or any other condition * Current use of phytoestrogens * Participation in another clinical study within 30 days prior to the start of the Study treatment

Locations (1)

Irmandade Da Santa Casa De Misericórdia De Santos - Science Valley Research Center

Santos, São Paulo, Brazil

Outcomes

Primary Outcomes

Serum total estradiol concentration

Multiple blood sample will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)

Time frame: 0, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days , 21 days , 28 days , 56 days, 84 days, 112 days, 140 days and 168 days

Area under the curve (AUC(0 ∞))

Multiple blood sample will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days , 21 days, 28 days, 56 days, 84 days ,112 days ,140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)

Time frame: 0, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days

Maximum concentration (Cmax)

Multiple blood sample will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)

Time frame: 0, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days

Time to reach maximum concentration (tmax)

Multiple blood sample will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS)

Time frame: 0, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days

Half Life (t1/2)

Data from ClinicalTrials.gov

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Secondary Outcomes

Total testosterone concentration

Multiple blood will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and total testosterone concentrations will be determined by Liquid chromatography - mass spectrometry

Time frame: Pre-insertion of the estradiol pellet; 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days,140 days and 168 days

Estrone concentration

Multiple blood will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours , 24 hours; 7 days, 14 days , 21 days , 28days , 56 days, 84 days, 112 days , 140 days and 168 days and estrone concentrations will be determined by LC-MS/MS.

Time frame: Pre-insertion of the estradiol pellet; 2h, 4h, 6h, 8h, 10h, 12, 24h; 7, 14, 21, 28, 56, 84, 112, 140 and 168 days

Follicle - stimulating hormone FSH concentration

Multiple blood will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and Follicle-stimulating hormone concentrations will be determined by electrochemiluminescence

Time frame: Pre-insertion of the estradiol pellet; 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days

Luteinizing hormone - hormone LH concentration

Multiple blood will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and Follicle-stimulating hormone concentrations will be determined by electrochemiluminescence

Sex hormone binding globulin SHBG concentration

Multiple blood will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days,28 dyas, 56 days, 84 days, 112 days, 140 days and 168 days and Follicle-stimulating hormone concentrations will be determined by electrochemiluminescence

Prolactin concentration

Multiple blood will be collected before pellet implantation and 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 7 days, 14 days, 21 days, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and Follicle-stimulating hormone concentrations will be determined by electrochemiluminescence