Clinical trial NCT06136208: Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women
Official title: Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women Comprehensive Longitudinal Assessment of Release With Estradiol Pellet Analysis (CLARA Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Climacteric Syndrome
Menopause
Hypoestrogenism
Keywords: Climateric
Estradiol Pellet
Menopause
Pharmacokinectic
Lead sponsor: Science Valley Research Institute
Sponsor class: OTHER
Collaborators: name: Biòs Farmacêutica
First posted: 2023-11-18
Enrollment: 20
Sex: FEMALE
Minimum age (years): 41
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A multicenter, prospective, open-label clinical study will be conducted, to monitor serum concentration and pharmacokinetic profile after subcutaneous implantation of a 25mg absorbable pellet containing estradiol in climacteric 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.

Eligibility criteria: 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)
* Hypoestrogenism defined by serum total estradiol concentration ≤ 50 pg/mL and serum FSH concentration ≥ 25 mIU/mL, both determined by immunoassays
* Presence of climacteric 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

Primary outcomes:
measure: Serum total estradiol concentration
timeFrame: 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
measure: Area under the curve (AUC(0 ∞))
timeFrame: 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
measure: Maximum concentration (Cmax)
timeFrame: 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
measure: Time to reach maximum concentration (tmax)
timeFrame: 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
measure: Half Life (t1/2)
timeFrame: 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
Secondary outcomes:
measure: Total testosterone concentration
timeFrame: 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
measure: Estrone concentration
timeFrame: Pre-insertion of the estradiol pellet; 2h, 4h, 6h, 8h, 10h, 12, 24h; 7, 14, 21, 28, 56, 84, 112, 140 and 168 days
measure: Follicle - stimulating hormone FSH concentration
timeFrame: 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
measure: Luteinizing hormone - hormone LH concentration
timeFrame: 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
measure: Sex hormone binding globulin SHBG concentration
timeFrame: 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
measure: Prolactin concentration
timeFrame: 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
Other outcomes:
measure: Adverse events
timeFrame: 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
measure: Change from baseline in the Menopause Rating Scale (MRS) score (global, psychological, somatic, and urogenital domains evaluated in clinical visits
timeFrame: 28 days, 84 days, and 168 days post-insertion of the estradiol pellet
Locations:
city: Santos
country: Brazil
facility: Irmandade Da Santa Casa De Misericórdia De Santos - Science Valley Research Center
state: São Paulo
Study officials:
affiliation: Science Valley Research Institute
name: André Luiz Malavasi de Oliveira Longo, MD, PhD
role: STUDY_CHAIR
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