Post-menopausal Osteoporosis MedDRA version: 9.1 Level: LLT Classification code 10031285 Term: Osteoporosis postmenopausal
Conditions
Interventions
Product Code: SB-751689-A
Pharmaceutical Form: Tablet
CAS Number: 702686-96-2
Current Sponsor code: SB-751689-A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Sponsors
GlaxoSmithKline Research and Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Informed consent: Subject is willing and able to provide written informed consent. 2. Menopausal status: Ambulatory female aged 5 years postmenopausal, which can be >5 years of spontaneous amenorrhea or > 5 years post surgical bilateral oophorectomy. Use follicle stimulating hormone [FSH] levels >40 mIU/mL to confirm surgical postmenopausal status, where bilateral oophorectomy status is uncertain. 3. T-Score: A subject with either no or only one prevalent vertebral fracture is eligible for inclusion if she satisfies one of the following T-score requirements: • If no prevalent vertebral fracture subject must have an absolute BMD value consistent with a T-score of less than or equal to -2.5 and greater than -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine, or • If one prevalent vertebral fracture subject must have an absolute BMD value consistent with a T-score of less than or equal to -2.0 and greater than -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine. Fracture is defined as having at least a 20% reduction in anterior, middle or posterior vertebral height determined by semi-quantitative DXA examination at the site. 4. Suitable vertebra: Two or more vertebra in the range of L1 to L4 that are suitable for BMD measurement by DXA. 5. Protocol compliance: Subject who, in the opinion of the investigator, is willing and able to comply with the requirements of the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. T-Score: Has an absolute BMD value consistent with a T-score less than or equal to -4.0 at either the femoral neck, total hip, trochanter, or lumbar spine. 2. Vertebral fractures: Has >1 prevalent vertebral fracture at the screening visit (where fracture is defined as having at least a 20% reduction in anterior, middle or posterior vertebral height determined by semi-quantitative DXA examination at the site). 3. Non-vertebral fractures: Any previous non-vertebral osteoporosis related/fragility fracture after age 40. 4. Biological abnormalities: Any clinically relevant biological abnormality found and/or volunteered at screening (other than those related to the disease under investigation) which, in the opinion of the investigator, is clinically significant and would preclude safe participation in this study [e.g., human immunodeficiency virus (HIV) infection, chronic hepatitis B and C (as evidenced by positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody), significant mental illness]. 5. Surgical and medical conditions: Presence of the following conditions within six months prior to screening: myocardial infarction, coronary bypass surgery, coronary artery angioplasty, unstable angina, cardiac arrhythmia, clinically evident congestive heart failure, or cerebrovascular accident. 6. Glomerular filtration rate: Glomerular filtration rate (GFR) <35 mL/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation as follows: GFR (mL/min/1.73 m2) = 186 x (Serum creatinine mg/dL)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American) (conventional units). 7. QT/QTc prolongation: A marked baseline prolongation of QT/QTc interval (e.g. QTc interval =450 msec on the Screening ECG). 8. Torsades de Pointes: A history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). 9. Liver chemistries: Liver chemistries [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase or total bilirubin] exceeding 2-fold the upper limit of the laboratory-specified reference range, at screening. 10. Abnormal serum calcium: Serum calcium (total or albumin-adjusted) outside the central laboratory reference range at the screening visit. 11. Abnormal PTH: PTH (intact or whole) outside the normal range. 12 Abnormal alkaline phosphatase: Alkaline phosphatase outside normal range 13 Oral bisphosphonates: Any previous treatment with an oral bisphosphonate as follows: • any treatment within the last six months • =one month cumulative treatment within the last 12 months • =three months cumulative treatment within the past two years, or • =two years cumulative treatment within the past five years. 14. Bone metabolism drugs: Treatment with other drugs affecting bone metabolism within the last six months prior to screening: • Chronic systemic corticosteroid [e.g., glucocorticoid, mineralocorticoid] treatment of no more than 2 intra-articular injections within the past year or use of oral, parenteral, or long-term, high-dose inhaled corticosteroids. Treatment with any topical corticosteroid will not exclude the subject from participating. • Hormones [e.g., estrogens/"natural estrogen preparations"(except for nonsystemic vaginal treatment), 19-norprogestins, SERMs such as raloxifene, anabolic steroids/androgens such as dehydroepiandrosterone (DHEA) or its sulfat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterise the dose-response for SB-751689 with respect to safety and efficacy based on BMD and biomarkers of bone turnover to enable dose selection for subsequent studies;Primary end point(s): The primary efficacy endpoint is percent change from baseline in BMD at Month 12 measured by DXA scans of the lumbar spine (L1-L4).;Secondary Objective: Secondary objectives are to evaluate safety and tolerability of SB-751689 administered for 12 months in post-menopausal women compared to placebo, alendronate and teriparatide, to demonstrate a statistically significant increase in BMD as measured by DXA at the lumbar spine following 6 and 12 months treatment with SB-751689 compared to placebo and a significant increase in BMD as measured by DXA at the total hip, femoral neck and trochanter following 6 and 12 months treatment with SB-751689. To investigate the effect of SB-751689 on biomarkers of bone turnover, on volumetric integral, cortical and trabecular density, cortical width and other parameters at the lumbar spine and hip as measured by QCT in a subset of study subjects, the effects on parameters of vertebral and hip strength as measured by QCT-derived finite element analysis, the effects on parameters of hip structural analysis as measured by DXA-derived data and the PK/PD relationship of SB-751689 in this study population. | — |
Countries
Denmark, Germany, Spain
Outcome results
None listed