Menopause Clinical Trial
— CLARAOfficial title:
Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women Comprehensive Longitudinal Assessment of Release With Estradiol Pellet Analysis (CLARA Study)
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.
Status | Recruiting |
Enrollment | 25 |
Est. completion date | October 30, 2024 |
Est. primary completion date | October 30, 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 41 Years to 59 Years |
Eligibility | Inclusion Criteria: - Signed Informed Consent Form - Woman aged = 41 and = 59 years - Weight = 50 kg and = 90 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 - Women with 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 |
Country | Name | City | State |
---|---|---|---|
Brazil | Irmandade Da Santa Casa De Misericórdia De Santos - Science Valley Research Center | Santos | São Paulo |
Lead Sponsor | Collaborator |
---|---|
Science Valley Research Institute | Biòs Farmacêutica |
Brazil,
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del Carmen Cravioto M, Larrea F, Delgado NE, Escobar AR, Diaz-Sanchez V, Dominguez J, de Leon RP. Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in postmenopausal Mexican women. Menopause. 2001 Sep-Oct;8(5):353-60. doi: 10.1097/00042192-200109000-00010. — View Citation
Hamoda H, Panay N, Pedder H, Arya R, Savvas M. The British Menopause Society & Women's Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health. 2020 Dec;26(4):181-209. doi: 10.1177/2053369120957514. Epub 2020 Oct 12. No abstract available. — View Citation
Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005 Aug;8 Suppl 1:3-63. doi: 10.1080/13697130500148875. — View Citation
Lobo RA, March CM, Goebelsmann U, Krauss RM, Mishell DR Jr. Subdermal estradiol pellets following hysterectomy and oophorectomy. Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes. Am J Obstet Gynecol. 1980 Nov 15;138(6):714-9. — View Citation
Lobo RA. Hormone-replacement therapy: current thinking. Nat Rev Endocrinol. 2017 Apr;13(4):220-231. doi: 10.1038/nrendo.2016.164. Epub 2016 Oct 7. — View Citation
Manson JE, Bassuk SS, Kaunitz AM, Pinkerton JV. The Women's Health Initiative trials of menopausal hormone therapy: lessons learned. Menopause. 2020 Aug;27(8):918-928. doi: 10.1097/GME.0000000000001553. — View Citation
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Owen EJ, Siddle NC, McGarrigle HT, Pugh MA. 25 mg oestradiol implants--the dosage of first choice for subcutaneous oestrogen replacement therapy? Br J Obstet Gynaecol. 1992 Aug;99(8):671-5. doi: 10.1111/j.1471-0528.1992.tb13853.x. — View Citation
Stanczyk FZ, Shoupe D, Nunez V, Macias-Gonzales P, Vijod MA, Lobo RA. A randomized comparison of nonoral estradiol delivery in postmenopausal women. Am J Obstet Gynecol. 1988 Dec;159(6):1540-6. doi: 10.1016/0002-9378(88)90591-1. — View Citation
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Suhonen SP, Allonen HO, Lahteenmaki P. Sustained-release subdermal estradiol implants: a new alternative in estrogen replacement therapy. Am J Obstet Gynecol. 1993 Nov;169(5):1248-54. doi: 10.1016/0002-9378(93)90291-p. — View Citation
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* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Adverse events | 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) | 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 | |
Primary | 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) | 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 | |
Primary | Area under the curve (AUC(0 8)) | 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) | 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 | |
Primary | 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) | 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 | |
Primary | 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) | 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 | |
Primary | Half Life (t1/2) | 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). | 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 | 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 | 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 | |
Secondary | 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 enzyme immunoassay. | Pre-insertion of the estradiol pellet; 2h, 4h, 6h, 8h, 10h, 12, 24h; 7, 14, 21, 28, 56, 84, 112, 140 and 168 days | |
Secondary | 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 | 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 | |
Secondary | 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 | 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 | |
Secondary | 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 | 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 | |
Secondary | 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 | 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 |
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