Effects of Teriparatide in the Treatment of Postmenopausal Women With Osteoporosis

Condition(s) targeted: Osteoporosis, Postmenopausal

Intervention: teriparatide (Drug); teriparatide (Drug); Placebo (Drug); Calcium Supplement (Drug); Vitamin D Supplement (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Eli Lilly and Company

Official(s) and/or principal investigator(s):
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), Study Director, Affiliation: Eli Lilly and Company

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.

Official title: Effects of LY333334 in the Treatment of Postmenopausal Women With Osteoporosis

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome:

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

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

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.

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.

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

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.

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)

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.

To quantify medical resources used by patients during the study so that a cost-effectiveness analysis can be performed.

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.

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.

Minimum age: 30 Years. Maximum age: 85 Years. Gender(s): Female.

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.

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Capital Federal, Argentina

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Nedlands, Australia

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Graz, Austria

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Brussels, Belgium

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Praha, Czech Republic

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Aarhus, Denmark

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Kuopio, Finland

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Szeged, Hungary

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Tel-Hashomer, Israel

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Arenzano, Italy

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Amsterdam, Netherlands

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Christchurch, New Zealand

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Kristiansand, Norway

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Warszawa, Poland

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Uppsala, Sweden

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Calgary, Alberta, Canada

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Boston, Massachusetts 02114, United States

Starting date: August 1996
Ending date: April 1999
Last updated: April 29, 2008