Osteoporosis, Postmenopausal
Conditions
Brief summary
The primary objective of this study is to demonstrate a reduction in the proportion of new vertebral fractures in postmenopausal women with osteoporosis following 3-years of treatment with 20 and 40 mcg/day of teriparatide plus calcium and vitamin D compared with calcium and vitamin D alone.
Interventions
DRUGteriparatide
40 micrograms/day subcutaneous injection for 3 years with optional 2 year extension phase
DRUGPlacebo
Placebo for subcutaneous injection will be supplied in a prefilled injection device with a cartridge identical in appearance to the LY333334 device.
Approximately 1000 mg/day of elemental calcium will be supplied as open-label oral supplement
Approximately 400 to 1200 IU/day of vitamin D will be supplied as open-label oral supplement
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Ambulatory, postmenopausal women. * A minimum of either one moderate or two mild atraumatic vertebral fractures, and a minimum of seven evaluable nonfractured vertebrae. * Hip BMD or lumbar spine BMD measurement at least 1.0 standard deviation (SD) below the average bone mass for young, healthy women (T-score) only in patients with fewer than two moderate fractures or in patients previously treated with therapeutic doses of bisphosphonates or fluorides * Normal or clinically nonsignificant abnormal laboratory values (serum calcium, PTH(1-84), & urine calcium must be within normal limits at baseline; 25-hydroxyvitamin D must be between the lower limit of normal & 3 times the upper limit of normal at baseline).
Exclusion criteria
* Fractures in areas of bone affected by diseases other than osteoporosis (for example, cancer or Paget's disease). * Satisfactory baseline thoracic and lumbar spinal x-ray views cannot be obtained as determined by the centralized x-ray quality assurance center (for example, severe scoliosis or kyphosis). * Current or recent (within 1 year prior to randomization) metabolic bone disorders other than postmenopausal osteoporosis, such as Paget's disease, renal osteodystrophy, osteomalacia, or any secondary causes of osteoporosis * Current or recent (within 1 year prior to randomization) disease which affects bone metabolism, such as hypoparathyroidism, hyperparathyroidism, or hyperthyroidism. * Currently suspected carcinoma or history of carcinoma in the 5 years prior to randomization. * Nephrolithiasis or urolithiasis in the 2 years prior to randomization. * Current or recent (within 1 year prior to randomization) sprue, inflammatory bowel disease, or malabsorption syndrome, or any indication of poor intestinal absorption of calcium, such as the combination of a low urinary calcium excretion and an elevated serum intact parathyroid hormone level. * Poor medical or psychiatric risk for treatment with an investigational drug, in the opinion of the investigator. * Treatment with androgens or other anabolic steroids in the 6 months prior to randomization. * Treatment with calcitonins in the 2 months prior to randomization. * Treatment with estrogen * Treatment with progestins in the 3 calendar months prior to randomization, or for more than 2 months in the 12 calendar months prior to randomization. * Treatment with corticosteroids. * Treatment with fluorides in the 6 months prior to randomization or for more than 60 days in the 24 months prior to randomization. * Treatment with oral bisphosphonates in the 3 months prior to randomization or for more than 60 days in the 24 months prior to randomization; treatment with intravenous bisphosphonates in the 24 months prior to randomization. * Treatment with vitamin D \>50,000 IU/week, or with any dose of calcitriol, analogs, or agonists in the 6 months prior to randomization. The 25-hydroxyvitamin D laboratory value at randomization must be between the lower limit of normal and three times the upper limit of normal. * Treatment with coumarins and indandione derivatives in the 3 months prior to randomization; treatment with heparins \>10,000 U/day for more than 30 days in the 6 months prior to randomization. * Treatment with calcium- or aluminum-containing antacids * Treatment with any other drug known to affect bone metabolism in the 6 months prior to randomization. * Treatment with any investigational drug during the month prior to the calcium and vitamin D run-in phase. Treatment with investigational drugs in certain therapeutic classes during the month prior to the calcium & vitamin D run-in phase.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate a reduction in the proportion of patients with new vertebral fractures (by spinal x-ray) following 3-year treatment with 20 and 40 micrograms/day of LY333334 plus calcium and vitamin D compared with calcium and vitamin D alone. | Baseline, randomization, 24 , 36, and 60 months |
Secondary
| Measure | Time frame |
|---|---|
| To establish the effect of long-term treatment with LY333334 plus calcium and vitamin D, compared with calcium and vitamin D alone, on total body and radial (forearm) BMD in postmenopausal women with osteoporosis at selected study sites | Randomization, 12, 24, 36, 48 and 60 months |
| To establish the effect of long-term treatment with LY333334 plus calcium and vitamin D, compared with calcium and vitamin D alone, on the rate of new vertebral fractures (by spinal x-ray) in postmenopausal women with osteoporosis. | Baseline, randomization, 24 months, 60 months |
| To establish the effect of treatment with LY333334 plus calcium & vitamin D, compared with calcium & vitamin D alone, by x-ray on the proportion of subjects experiencing new nonvertebral fractures alone & new nonvertebral & vertebral fractures combined. | As clinically needed throughout the trial |
| To assess the effect of long-term treatment with LY333334 plus calcium and vitamin D, compared with calcium and vitamin D alone, on height (via Harpenden stadiometer or other suitable stadiometer) in postmenopausal women with osteoporosis | Randomization, 12, 24, 36, 48, and 60 months |
| To determine the histomorphometric effects of LY333334 plus calcium & vitamin D, compared with calcium & vitamin D alone by biopsy, on the iliac crest (bone formation & resorption, mineralization, and trabecular structure) in a subset of subjects. | Randomization, 12 and 24 months |
| To establish the effect of long-term treatment with LY333334 plus calcium and vitamin D, compared with calcium and vitamin D alone, on lumbar spine and hip BMD in postmenopausal women with osteoporosis | Lumbar Spine: Randomization -2wks, Randomization,( 3 & 6 months in a subset of pts), 12 , 18 , 24 , 36 , 48 & 60 months. Hip BMD: Randomization -2wks, Randomization, 12 , 24 , 36 , 48 & 60 months. |
| To assess population pharmacokinetics of LY333334 at selected study sites. Nonlinear mixed effect modeling [NONMEM])and or PTH(1-84) will be employed to evaluate serum concentrations of LY333334. | Months 1, 3, 6, 12, 18, 24, 30, 36 and 60 |
| To quantify medical resources used by patients during the study so that a cost-effectiveness analysis can be performed. | Randomization, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 Months |
| To assess the impact of LY333334 on health-related quality of life in postmenopausal women with osteoporosis. Quality of life instruments will be completed where translated and validated instruments are available. | Randomization, 12, 24, 36, 48, and 60 months |
| To establish the safety of chronic administration of LY333334 in postmenopausal women with osteoporosis. Adverse events, physical examinations and laboratory tests will be used to assess safety in the patients. | Adverse Events: throughout the trial. Labs:Baseline, randomization, 1, 6, 12, 24, 36, 48, and 60 months. Physical Exams: 12, 24, 36, 48, and 60 months |
| To assess effects of LY333334 plus calcium & vitamin D, compared with calcium & vitamin D alone, on biochemical markers of bone formation & resorption (bone-specific alkaline phosphatase, PICP, urinary N-telopeptide, & urinary free deoxypyridinolines) | Randomization, 1, 3, 6, 12, 24, 36, 48, and 60 months |
Countries
Argentina, Australia, Austria, Belgium, Canada, Czechia, Denmark, Finland, Hungary, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Sweden, United States
Outcome results
None listed