Comparison of the Effects of 2 Drugs on Lumbar Spine Volumetric BMD in Men With Glucocorticoid-Induced Osteoporosis (EuroGIOPS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00503399
First received: July 16, 2007
Last updated: March 12, 2012
Last verified: October 2011
  Purpose

The objective of this study is to test the hypothesis that teriparatide is superior to the active comparator in the change from baseline to 18 months of lumbar spine volumetric trabecular bone mineral density (BMD) in males with glucocorticoid-induced osteoporosis.


Condition Intervention Phase
Osteoporosis
Drug: Teriparatide
Drug: Risedronate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of the Effects of Teriparatide With Those of Risedronate on Lumbar Spine vBMD in Glucocorticoid-Induced Osteoporosis in Men

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Tomography (QCT) at 18 Months [ Time Frame: Baseline, 18 months ] [ Designated as safety issue: No ]
    Least Squares (LS) Means were adjusted for age, baseline serum aminoterminal propeptide of Type I procollagen (P1NP), fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.


Secondary Outcome Measures:
  • Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Technology (QCT) at 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    Least Squares (LS) Means were adjusted for age, baseline propeptide of Type I procollagen (P1NP), fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.

  • Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months [ Time Frame: Baseline, 6 months, 18 months ] [ Designated as safety issue: No ]
    Three-dimensional (3-D) microstructure variables of T12 were assessed by HR-QCT. In contrast with regular QCT that assessed 3 millimeter (mm) slide thickness, HR-QCT used segmentation of 1 single vertebra with approximately 100 consecutive slides reconstructed at 300-400 micrometer (µm) slice increments covering the complete vertebral body. Least Squares (LS) Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.

  • Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength [ Time Frame: Baseline, 6 months, 18 months ] [ Designated as safety issue: No ]
    Anterior bending and axial torsion were measured using HR-QCT-based finite element analysis to determine stiffness and strength of T12. Stiffness evaluated strength of the vertebral body, defined as the slope of the initial step of the force-displacement curve. Strength of the vertebral body was evaluated under compressive loading conditions using computer simulation. LS Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.

  • Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength [ Time Frame: Baseline, 6 months, 18 months ] [ Designated as safety issue: No ]
    Axial compression was measured using HR-QCT-based finite element analysis to determine stiffness and strength of T12. Stiffness evaluated the strength of the vertebral body, defined as the slope of the initial step of the force-displacement curve. Strength of the vertebral body was evaluated under compressive loading conditions using computer simulation. LS Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.

  • Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months [ Time Frame: Baseline, 18 months ] [ Designated as safety issue: No ]
    Dual x-ray absorptiometry (DXA) techniques validated this measurement at skeletal sites that are at risk of osteoporotic fracture, such as lumbar spine, femoral neck, and hip.

  • Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months [ Time Frame: Baseline, 3 months, 6 months, 18 months ] [ Designated as safety issue: No ]
    P1NP was used as a serum biochemical marker of collagen synthesis, reflecting the formation of new osteoid.

  • Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months [ Time Frame: 3, 6, 18 months ] [ Designated as safety issue: No ]
    β-CTx was used as a biochemical marker of bone turnover/resorption, reflecting collagen breakdown of the bone matrix.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 18 months ] [ Designated as safety issue: Yes ]
    Summary tables of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module. Fractures that occurred during the study were collected separately as an additional safety variable. The number of participants experiencing hypercalcemia was summarized for each treatment arm. Hypercalcemia was defined as a serum calcium level corrected for albumin of >2.7 millimole per liter (mmol/L) (10.8 milligram per deciliter [mg/dL]).


Enrollment: 92
Study Start Date: July 2007
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriparatide
Teriparatide 20 microgram (µg) subcutaneous (sc) injection once daily (QD).
Drug: Teriparatide
20 µg/day sc for 18 months
Other Names:
  • LY333334
  • Forteo
  • Forsteo
Active Comparator: Risedronate
Risedronate 35 milligrams (mg) oral (po) tablet once weekly (QW)
Drug: Risedronate
35 mg/week po for 18 months
Other Name: Actonel

Detailed Description:

This study is a multinational, European, multicenter, randomized, open-label, active comparator controlled study with 2 study periods: a screening phase of up to 6 weeks, and an open-label treatment phase of 18 months. Approximately 100 adult men with osteoporosis associated with sustained glucocorticoid therapy will be enrolled into the study. Approximately one-half of the participants (at all investigational sites) will be randomized to teriparatide 20 micrograms/day (ug/day given as a subcutaneous (sc) injection), and the other half randomized to risedronate 35 milligrams (mg) once weekly (QW) oral (po) tablet. All participants will receive approximately 1000 mg/day elemental calcium and 800 to 1200 international units per day (IU/day) of vitamin D.

  Eligibility

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ambulatory men 25 years of age and older presenting to Visit 1 with a bone mineral density (BMD) of at least 1.5 standard deviation (SD) below the corresponding normal young adult men average BMD (T score of -1.5 or lower), as determined from the manufacturer's database at any of the following regions of interest: total hip, femoral neck, or lumbar spine
  • Have received glucocorticoid therapy at an average dose of at least 5.0 milligrams (mg) per day of prednisone or its equivalent for a minimum of 3 consecutive months immediately preceding screening (Visit 1), as determined by medical history.
  • A minimum of 2 lumbar vertebrae (L) in the L-1 through L-3 region must be evaluable by quantitative computerized tomography.
  • Normal or clinically insignificant abnormal laboratory values (as determined by the investigator) including serum calcium, parathyroid hormone (PTH) (1 84), and 25 hydroxyvitamin D concentrations, and alkaline phosphatase activity.

Exclusion Criteria:

  • Presence of a mild, moderate, or severe spinal fracture in both the twelfth thoracic vertebra (T-12) and first lumbar vertebra (L-1), as determined by the central reading facility using the semiquantitative technique.
  • Abnormal albumin-corrected serum calcium levels
  • History of unresolved skeletal diseases that affect bone metabolism other than glucocorticoid-induced osteoporosis
  • History of malignant neoplasms in the 5 years prior to Visit 2, with the exception of superficial basal cell or squamous cell carcinomas of the skin that have been definitively treated. Increased baseline risk of osteosarcoma; this includes patients with Paget's disease of the bone, previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation.
  • Abnormal thyroid function not corrected by therapy
  • Past and/or current treatment with certain medications.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00503399

Locations
Germany
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.
Bad Nauheim, Germany, 61231
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Frankfurt, Germany, 60528
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Hamburg, Germany, 22415
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Heinsberg, Germany, 52525
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Leverkusen, Germany, 51375
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Magdeburg, Germany, 39110
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Potsdam, Germany, 14469
Greece
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Kifissia, Greece, 14561
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Thessaloniki, Greece, 56429
Italy
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Rome, Italy, 00161
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Siena, Italy, 53100
Spain
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.
Barcelona, Spain, 08907
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.
Madrid, Spain, 28046
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (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

Additional Information:
No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00503399     History of Changes
Other Study ID Numbers: 11716, B3D-EW-GHDH
Study First Received: July 16, 2007
Results First Received: October 4, 2011
Last Updated: March 12, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: Ethics Committee
Spain: Spanish Agency of Medicines

Keywords provided by Eli Lilly and Company:
Glucocorticoid Induced

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Glucocorticoids
Risedronic acid
Teriparatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014