postmenopausal women with high risk for osteoporosis MedDRA version: 7.0 Level: LLT Classification code 10050213
Conditions
Interventions
Product Name: SH T 04170 E
Product Code: DE-04170
Pharmaceutical Form: Tablet
INN or Proposed INN: estradiol
CAS Number: 35380-71-3
Current Sponsor code: ZK 5018
Other descriptive name: b-Estradiol h
Sponsors
Schering AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 55 years and = 80 years (at visit 1) 2. Last (regular) menstrual period = 5 years ago (at visit 2) 3. Intact, normal uterus and an endometrial biopsy result confirming absence of hyperplasia or any relevant pathology 4. Evaluable BMD by DXA of the lumbar spine (AP view, L1-L4; at least 2 vertebrae should be evaluable), femoral neck, and total hip 5. Mean pretreatment BMD T score =-1 and =-2.5 at the lumbar spine (L1-L4) 6. Presence of at least one additional risk factor to develop osteoporosis as listed below: - Mother, father or sister with history of low trauma fracture or osteoporosis - Body mass index (BMI) =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Current bone and musculoskeletal diseases, e.g., Morbus Scheuermann, osteogenesis imperfecta, hypo- or hyper-parathyroidism, Paget’s disease, osteomalacia, or other metabolic disease of bone; hypo- or hypercalcemia, vitamin D deficiencies 2. History of immobilization > 2 months in the last 6 months before visit 1 3. History of clinically significant vertebral fracture within the last 12 months before visit 1 4. Patients requiring specific anti-osteoporotic treatment according to the investigator’s judgement 5. Any uterine bleeding within the last year before visit 1 6. Cervical smear with abnormal result (Pap: C III or worse) 7. Pre-existing cardiovascular disease - Uncontrolled hypertension; sitting systolic blood pressure = 180 mm Hg or sitting diastolic blood pressure = 105 mm Hg after at least 10 minutes rest (at either visits 1 or 2) - History of stroke, transient ischemic attacks and myocardial infarction, or angiographic evidence of 50% narrowing of one or more coronary arteries, or heart disease requiring anti-arrhythmic or anti-anginal drug treatment, or congestive heart failure - History or planned coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, coronary stenting - Existing or history of venous thromboembolic event (including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis) at any time and any condition which might increase the risk to suffer from any of the mentioned disorders, or known or suspected genetical component thereof (e.g., positive family history, event that occurred in a sibling or a parent at an early age), or current treatment with anticoagulants 8. Laboratory values as defined as clinically significant by the sponsor (see 7.5.1.3.10 and protocol attachment 3) and/or assessed as significantly abnormal by the investigator 9. Uncontrolled diabetes mellitus or diabetes mellitus currently treated with insulin 10. Uncontrolled thyroid disorders, or initiation or change in dose of thyroid replacement therapy within 6 months 11. Relevant renal disorder or significant liver dysfunction (including cholestasis and porphyria) 12. Current or past history of clinically significant depression 13. Malignant or premalignant disease within the last 5 years (except for superficial skin cancer) 14. Sex steroid (hormone)-dependent malignant disease at any time 15. Any other systemic or gynecologic disorder, laboratory finding, or ultrasound finding which might worsen under study drug treatment, might interfere with the conduct of the study or the interpretation of the results 16. Any disease or condition that compromises the function of the body system and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study medication 17. Intake or use of the following medications (before visit 1 or during the study) - Within 4 weeks before visit 1: estrogen or progestin therapy (oral, transdermal, intrauterine or intravaginal administration, or estrogen implants), for intramuscular depot injections wash-out phase of 6 months - Within 3 months before visit 1: raloxifene, fluoride, or calcitonin - If taken for a duration > 3 months within the past 2 years: bisphosphonates, parathyroid hormone - Currently taking GnRH agonists or antagonists, therapeutic vitamin D analogues - Currently taking: systemic corticosteroids, high dose multivitamins, or other agents which are known or suspected to affect bone metabolism - Currently
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this study is to evaluate the efficacy and safety of 2 different low-dose E2 preparations (SHT04170E – 100 µg E2; SHT04170F – 190 µg E2) for the prevention of postmenopausal osteoporosis in women who are at least 5 years postmenopausal over a treatment period of 2 years (26 cycles of 28 days) compared to placebo. Efficacy will be assessed by BMD measurements of the lumbar spine (L1-L4), femoral neck, and total hip.;Secondary Objective: A secondary objective will be endometrial safety and the evaluation of differences in E2 and E1 exposure between the treatment groups. This evaluation will be based on population pharmacokinetic analyses of E2 and E1 concentrations in the targeted patient population. The relationship of E2 and E1 with SHBG will be studied in an explorative way. Additionally, the influence of covariates (i.e., age, weight, race, and concomitant medication) on pharmacokinetic parameters of E2 and E1, like clearance (CL) and volume of distribution (V), will be explored. ;Primary end point(s): The primary efficacy variable is the percent change in the BMD at the lumbar spine (L1-L4) from pretreatment to the final visit (visit 7). With respect to the 2 pretreatment measurements, the arithmetic mean of the BMD measurements by DXA from screening (visit 1) will be used. With respect to the 2 final visit measurements, the arithmetic mean of the BMD measurements by DXA after 2 years of treatment at the final visit (visit 7) will be used. | — |
Countries
Czech Republic, Denmark
Outcome results
None listed