Effects of Teriparatide in the Treatment of Postmenopausal Women With Osteoporosis

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00670501
First received: April 29, 2008
Last updated: NA
Last verified: April 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Osteoporosis, Postmenopausal
Drug: teriparatide
Drug: Placebo
Drug: Calcium Supplement
Drug: Vitamin D Supplement
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of LY333334 in the Treatment of Postmenopausal Women With Osteoporosis

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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. [ Time Frame: Baseline, randomization, 24 , 36, and 60 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Randomization, 12, 24, 36, 48 and 60 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Baseline, randomization, 24 months, 60 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: As clinically needed throughout the trial ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Randomization, 12, 24, 36, 48, and 60 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Randomization, 12 and 24 months ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Randomization, 1, 3, 6, 12, 24, 36, 48, and 60 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Months 1, 3, 6, 12, 18, 24, 30, 36 and 60 ] [ Designated as safety issue: No ]
  • To quantify medical resources used by patients during the study so that a cost-effectiveness analysis can be performed. [ Time Frame: Randomization, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 Months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Randomization, 12, 24, 36, 48, and 60 months ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

Enrollment: 1637
Study Start Date: August 1996
Study Completion Date: April 1999
Primary Completion Date: April 1999 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
LY333334 40 micrograms/day plus calcium and vitamin D
Drug: teriparatide
40 micrograms/day subcutaneous injection for 3 years with optional 2 year extension phase
Other Names:
  • LY333334
  • Forteo
  • Forsteo
Drug: Calcium Supplement
Approximately 1000 mg/day of elemental calcium will be supplied as open-label oral supplement
Drug: Vitamin D Supplement
Approximately 400 to 1200 IU/day of vitamin D will be supplied as open-label oral supplement
Experimental: 2
LY333334 20 micrograms/day plus calcium and vitamin D
Drug: teriparatide
20 micrograms/day subcutaneous injection for 3 years with optional 2 year extension phase
Other Names:
  • LY333334
  • Forteo
  • Forsteo
Drug: Calcium Supplement
Approximately 1000 mg/day of elemental calcium will be supplied as open-label oral supplement
Drug: Vitamin D Supplement
Approximately 400 to 1200 IU/day of vitamin D will be supplied as open-label oral supplement
Placebo Comparator: 3
Placebo plus calcium and vitamin D
Drug: Placebo
Placebo for subcutaneous injection will be supplied in a prefilled injection device with a cartridge identical in appearance to the LY333334 device.
Drug: Calcium Supplement
Approximately 1000 mg/day of elemental calcium will be supplied as open-label oral supplement
Drug: Vitamin D Supplement
Approximately 400 to 1200 IU/day of vitamin D will be supplied as open-label oral supplement

  Eligibility

Ages Eligible for Study:   30 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00670501

  Show 17 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CT LILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00670501     History of Changes
Other Study ID Numbers: 547, B3D-MC-GHAC
Study First Received: April 29, 2008
Last Updated: April 29, 2008
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium, Dietary
Vitamin D
Ergocalciferols
Teriparatide
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 16, 2014