Osteoporosis
Conditions
Interventions
Product Name: SB-462795 tablets
Product Code: SB-462795
Pharmaceutical Form: Tablet
CAS Number: 362505-84-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Phar
Sponsors
GlaxoSmithKline Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects who have signed informed consent. 2. Ambulatory postmenopausal women 40 mIU/ml can be used to confirm surgical postmenopausal status). 3. Subjects who, in the opinion of the investigator, are willing and able to comply with the protocol requirements. 4. BMD T-Score =-2.0 at the femoral neck, total hip, or lumbar spine at the Screening visit. All subjects must have BMD T-scores > -3.5 at all three sites at the Screening visit. 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: 1. Any previous osteoporotic fracture or previously documented Grade 2 or worse prevalent vertebral fracture or one or more Grade 2 or 3 vertebral fracture(s) identified by baseline vertebral fracture assessment (VFA) of the spine. 2. Less than three vertebra in the range of L1 to L4 that are suitable for BMD measurement by DXA. 3. Significant spine deformity which would preclude VFA assessment. 4. History of hip surgery resulting in a metal implant which would cause artifact on a CT scan. 5. Subjects with a history of, or ongoing diffuse collagen related diseases or autoimmune related diseases 6. Subjects with localized morphea or Raynaud’s phenomenon. 7. A marked baseline prolongation of QT/QTc interval 8. A history of additional risk factors for Torsades de Pointes 9. Any clinically relevant biological abnormality found 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 10. Malignant disease diagnosed within the previous 5 years (except resected basal cell cancer). 11. History of major upper gastrointestinal disease defined by: • Significant upper gastrointestinal bleeding within the last year requiring hospitalization or transfusion; • Recurrent peptic ulcer disease documented by radiographic or endoscopic means; • Dyspepsia or gastroesophageal reflux that is uncontrolled by medication; • Abnormalities of the esophagus that delay esophageal emptying, such as stricture, achalasia, or dysmotility; • Active gastric/duodenal ulcers; • Subjects are not excluded because of previous or active gastrointestinal disease , except as outlined above. 12. Malabsorption syndrome 13. Inability to swallow a tablet whole. 14. Contraindications to therapy with calcium, vitamin D or alendronate. 15. Administration of any investigational drug within 90 days preceding the first dose of the study drug. 16. History or current evidence of drug or alcohol abuse within the previous 12 months. 17. Other than osteoporosis, history or concurrent diseases affecting bone metabolism. Subjects receiving thyroid hormone replacement therapy must be on a stable dosing regimen for at least 3 months prior to screening. 18. 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 19. Any previous treatment with intravenous bisphosphonate. 20. Treatment with strontium ranelate within the past year. 21. Treatment with fluoride for osteoporosis (dose greater than 10mg/day) within the last 12 months, or past treatment for more than a total of two years. 22. Treatment with PTH or similar anabolic agent for osteoporosis within the last two years. 23. Treatment with other drugs affecting bone metabolism within the last six months prior to screening: • chronic systemic corticosteroid treatment (oral, parenteral, intra-articular, or long-term, high-dose inhaled) except for topical treatment at a frequency of up to twice per week • hormones [e.g., estrogens/"natural estrogen preparations"(except for topical treatment at a frequency of up to twice per week), 19-norprogestins, SERM such as raloxifene, anabolic steroids/androgens such as dehydroepiandrosterone (DHEA) or its sulfate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate significant improvement in areal lumbar spine BMD in at least one SB-462795 treatment group compared to placebo. ;Secondary Objective: • Determine an effective dose range for SB-462795 to enable dose selection for subsequent efficacy studies • Assess the safety & tolerability of SB-462795. • Estimate effects of SB-462795 on volumetric density of cortical and trabecular bone and cortical width and volume at the lumbar spine and hip. • Assess effects of SB-462795 on areal hip BMD. • Evaluate the effects of SB-462795 on bone resorption and formation markers. • Assess effects of SB-462795 on parameters of cortical and trabecular bone quality based on the bone biopsies using histomorphometry and micro computed tomography (µCT). • Assess pharmacokinetic (PK) effects of SB-462795 through population PK. ;Primary end point(s): Change from Baseline BMD at Month 12, as measured by DXA scans of the lumbar spine (L1-L4). | — |
Countries
United Kingdom
Outcome results
None listed