A Double Blind, Placebo Controlled, Parallel-Group Study to Assess the Safety and Efficacy of 3 Doses of ALX1-11 (50, 75, and 100µg) in the Treatment of Postmenopausal Osteoporosis
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
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Efficacy was assessed as percent change from baseline in BMD, BMC, and BMA at the lumbar spine, total hip, femoral neck and whole body (excluding the head) using DXA.
United States: Food and Drug Administration
|John Wayne Cancer Institute||Santa Monica, California 90404|
|Longmont Medical Research Network||Longmont, Colorado 80501|
|Pivotal Research||Peoria, Arizona 85381|
|Loma Linda Osteoporosis Research Clinic||Loma Linda, California 92354|
|Steven Harris||Mill Valley, California 94941|
|Paul Miller||Lakewood, Colorado 80227|
|Radiant Research, Stuart||Stuart, Florida 34996|
|Maine Center for Osteoporosis Research and Education of St. Joseph's Hospital||Bangor, Maine 04401|
|'Bethesda Health Research Center||Bethesda, Maryland 20817|
|Helen Hayes Hospital||West haverstraw, New York 10993|
|Oregon Osteoporosis Center||Portland, Oregon 97213|
|Simona Scumpia||Austin, Texas 78758|
|Radiant Research, Dallas||Dallas, Texas 75235|
|'Diabetes & Glandular Disease Research Associates, P.A.||San Antonio, Texas 78229|
|Northwest Lipid Research Center||Seattle, Washington 98104|