Climacteric Syndrome, Hypoestrogenism, Menopause
Conditions
Keywords
Climateric, Estradiol Pellet, Menopause, Pharmacokinectic
Brief summary
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.
Detailed description
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.
Interventions
DRUGs.c 25 mg estradiol pellet
Subcutaneous insertion of 25 mg estradiol pellet.
Sponsors
Biòs Farmacêutica
Science Valley Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
41 Years to 59 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach maximum concentration (tmax) | 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 | 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) |
| Half Life (t1/2) | 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 | 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 dyas, 28 days, 56 days, 84 days, 112 days, 140 days and 168 days and will be determined by liquid chromatography (LC-MS/MS). |
| Serum total estradiol concentration | 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 | 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) |
| Area under the curve (AUC(0 ∞)) | 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 | 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) |
| Maximum concentration (Cmax) | 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 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prolactin concentration | 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 | 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 | 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 | 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 |
| Total testosterone concentration | 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 | 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 |
| Estrone concentration | Pre-insertion of the estradiol pellet; 2h, 4h, 6h, 8h, 10h, 12, 24h; 7, 14, 21, 28, 56, 84, 112, 140 and 168 days | 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. |
| Follicle - stimulating hormone FSH concentration | 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 | 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 |
| Luteinizing hormone - hormone LH concentration | 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 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | pre-insertion of the estradiol pellet; 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours; 28 days, 84 days, and 168 days | Number of participants experiencing serious adverse events (SAEs) and adverse events leading to discontinuation in the study. Adverse events reported by study participants (any including non-serious ones) |
| Change from baseline in the Menopause Rating Scale (MRS) score (global, psychological, somatic, and urogenital domains evaluated in clinical visits | 28 days, 84 days, and 168 days post-insertion of the estradiol pellet | The MRS is a patient reported assessment of 11 symptoms of menopause on a scale of 0 (none) to 4 (very severe). The MRS groups symptoms into three subscales: psychological, somatic, and urogenital. A composite score is calculated by adding the items in each dimension (subscale). The total score is the sum of the three dimensional scores. A higher score indiactes a greater severity of perceived menopausal symptoms. |
Countries
Brazil
Outcome results
None listed