Study CR9108963: a Dose-Range Finding Study of SB-751689 in Post-Menopausal Women with Osteoporosis

INTERVENTION: 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‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use 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: 200‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use 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: 300‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use 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: 400‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Fosamax 70 mg Product Name: Fosamax 70 mg Pharmaceutical Form: Capsule, hard INN or Proposed INN: Alendronate sodium trihydrate Other descriptive name: Fosamax 70 mg Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 70‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Forsteo Product Name: Forsteo Pharmaceutical Form: Injection* INN or Proposed INN: Teriparatide Other descriptive name: Forsteo Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 20‐ CONDITION: Post‐menopausal Osteoporosis ; MedDRA version: 9.1 Level: LLT Classification code 10031285 Term: Osteoporosis postmenopausal PRIMARY OUTCOME: 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. 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 < 80 years at screening and >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