Human clinical experience with a synthetic human parathyroid hormone fragment (rhPTH 1-34) and animal studies with ALX1-11 demonstrate consistent increases in bone mineral density. Furthermore, the newly formed bone is normal in structure and composition. Therefore, ALX1-11 (recombinant human parathyroid hormone [rhPTH 1-84]) has the potential to stimulate new bone formation in osteoporotic patients thereby increasing trabecular bone density and preventing fractures. The clinical profile for ALX1-11 can be expected to be unique, since none of the approved therapies for osteoporosis are able to form the quantities of new bone that ALX1-11 is potentially capable of. Patients with bone density below the fracture threshold (osteopenia), as well as those with established vertebral fractures (osteoporosis), would be expected to benefit from treatment.~Animal toxicology studies have been completed and there were no results to indicate any restrictions in the clinical usage of the drug. Preliminary human clinical experience with ALX1-11 in healthy, postmenopausal females has demonstrated no apparent risk of frank hypercalcemia* at single administrations up to 5.0 µg/kg or daily administrations for 7 days up to 2.0 µg/kg/day.~Based on these studies, the anticipated therapeutic range of ALX1-11 is 50-100 µg per day (approx. 1.0 - 1.5 µg/kg/day). Therefore, the dose range to be tested in this study will include an anticipated minimally effective dose, interim dose and maximally tolerable dose (50, 75 and 100 µg). The efficacy of 3 doses of ALX1-11 will be assessed in terms of bone mineral density and biochemical markers of bone turnover in postmenopausal women.~The primary objective of this study is to determine the dose-response relationship of ALX1-11 in terms of bone mineral density. The efficacy of the 3 doses of ALX1-11 relative to placebo will be determined by measurement of bone mineral density (by DXA) at baseline and at 3, 6 and 12 months.~Patients will administer a daily subcutaneous injection of 0.5 mL of either 50, 75 or 100 µg of ALX1-11 or placebo every morning for 12 months.~Women will be advised to use the provided calcium supplements (500mg elemental calcium) to maintain a total daily intake of 1000-1500 mg/day and vitamin D supplements will also be provided (400 IU/day). A dietary questionnaire will be done at visit screen, 6 and 15.~If a patient's total serum calcium measurement, during the treatment phase, demonstrates frank hypercalcemia OR if her pre-dose calcium levels are more than 0.5 mg/dL or 0.125 mmol/L above the upper limit of normal (2.78 mmol/L or 11.1 mg/dL), then the patient's serum calcium level must be repeated.~If upon re-test a patient continues to demonstrate frank hypercalcemia OR if her basal pre-dose calcium levels continues to be elevated above the upper limit of normal, then the patient will be withdrawn from the study.~*Frank Hypercalcemia: defined as total serum calcium levels above 11.1 mg/dL or 2.78 mmol/L
A double-blind, placebo-controlled, parallel-group study to assess the safety and efficacy of 3 doses of ALX1-11 (recombinant human parathyroid hormone [rhPTH(1-84)])(50, 75 and 100 µg) in the treatment of postmenopausal osteoporosis. The primary objective of this study is to compare the efficacy of ALX1-11 (50, 75 and 100 µg) with that of placebo in terms of increasing vertebral bone mineral density, when given daily by subcutaneous injection for 12 months in postmenopausal women with osteoporosis.