Table 3. Study programs involving investigational osteoporosis drugs.
Trial | n | Primary endpoint | Main results | Ref. |
---|---|---|---|---|
DENOSUMAB | ||||
Phase 1 | ||||
Single-dose placebo-controlled study in postmenopausal women | 49 | Biochemical markers of bone resorption after 6 months vs. placebo | Urinary NTX decreased by 81% (3 mg/kg denosumab) vs. −10% with placebo (p<0.001) | Bekker50 |
Phase 2 | ||||
Efficacy and safety in postmenopausal women with low bone mineral density | 412 | % change from baseline BMD at the lumbar spine after 12 months vs. placebo | Lumbar spine BMD +3.0% to +6.7% vs. −0.6% with placebo (p<0.001) | McClung51 |
Phase 3 | ||||
Treatment of postmenopausal osteoporosis (FREEDOM) | 7,868 | Reduction of new vertebral fractures after 36 months vs. placebo | Vertebral fractures decreased by 68% (RR: 0.32, 95%CI 0.26–0.41); hip fractures decreased by 40% (RR: 0.60, 95%CI 0.37–0.97) | Cummings55 |
Prevention of postmenopausal osteoporosis | 332 | % change from baseline BMD at the lumbar spine after 24 months vs. placebo | Lumbar spine BMD +6.5% vs. −0.6% with placebo (p<0.0001) | Bone57 |
Comparison with alendronate in postmenopausal Women with low bone mineral density (DECIDE) | 1,189 | % change from baseline BMD at the total hip after 12 months vs. alendronate | Total hip BMD +3.5% vs. +2.6% with alendronate (p<0.0001) | Brown56 |
Treatment of bone loss in men on androgen-deprivation therapy for non-metastatic prostate cancer (HALT) | 1,468 | % change from baseline BMD at the lumbar spine after 24 months | Lumbar spine BMD +5.6% vs. −1.0 with placebo (p<0.001). After 36 months, vertebral fractures decreased by 62% (RR: 0.38; 95%CI 0.19–0.78) | Smith61 |
Treatment of bone loss in women on aromatase inhibitors for non-metastatic breast cancer | 252 | % change from baseline BMD at the lumbar spine after 12 months | Lumbar spine BMD +5.5% vs. placebo (p<0.0001) | Ellis60 |
ODANACATIB | ||||
Phase 1 | ||||
Multiple oral doses in healthy adults | 62 | Safety and tolerability | No increase in adverse events; serum CTX decreased by 62% (50 or 100 mg per week) BSAP and osteocalcin remained unaffected | Stoch64 |
Once-weekly doses in healthy adult females | 78 | |||
Phase 2 | ||||
Treatment of postmenopausal osteoporosis | 399 | % change from baseline BMD at the lumbar spine after 24 months | Lumbar spine BMD +5.5% vs. −0.2% with placebo | Bone65 |
Phase 3 | ||||
Treatment of postmenopausal osteoporosis | 16,716 | Vertebral, hip, and clinical non-clinical fractures after 36 months | Expected to be completed in July 2012 | NCT00529373 |
ONO-5334 | ||||
Postmenopausal women with low BMD | 265 | % change from baseline BMD at the lumbar spine after 12 months | Completed in October 2009, results pending | NCT 00532337 |
SARACATINIB | ||||
Phase 1 | ||||
Multiple oral doses on bone turnover in healthy men | 59 | Effect on bone turnover of multiple daily oral dosing for up to 24 days | Serum CTX −88% (95%CI 84–91%) vs. +17% with placebo (p<0.001); PINP +13 vs. +17% with placebo (p=NS) | Hannon67 |
MK-5442 (Calcilytic agent) | ||||
Phase 2 | ||||
Dose-ranging study in postmenopausal osteoporosis | 384 | % change from baseline BMD at the lumbar spine after 12 months | Expected to be completed in February 2012 | NCT00960934 |
Postmenopausal osteoporosis previously treated with alendronate | 480 | % change from baseline BMD at the lumbar spine vs. alendronate after 12 months | Expected to be completed in August 2012 | NCT00996801 |
AMG 785 (Antibody against sclerostin) | ||||
Phase 1 | ||||
Healthy men and postmenopausal women | 74 | Safety | No increase in adverse events; after 21 days 3 mg/kg increased PINP, osteocalcin and BSAP by 60 to 100% | NCT01059435 |
Phase 2 | ||||
Postmenopausal women with low BMD (vs. alendronate and teriparatide) | 419 | % change from baseline BMD at the lumber spine after 12 months | Expected to be completed in August 2012 | NCT00896532 |
BHQ 880 (Antibody against dickkopf-1) | ||||
Phase 1/2 | ||||
Combination with zoledronic acid in relapsed or refractory myeloma patients | 267 | Time to skeletal-related event; SRE, changes in bone resorption and formation markers after 9 months | Expected to be completed in November 2010 | NCT00741377 |
Abbreviations: BSAP, bone-specific alkaline phosphatase; CTX, C-terminal telopeptide of type I collagen; NTX, N-terminal telopeptide of type I collagen; PINP, serum procollagen propeptide of type I collagen.