Back to resultsDouble-blind Extension of HORIZON Pivotal Fracture Trial (Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis)
Primary Purpose
Osteoporosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Zoledronic Acid
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoporosis focused on measuring Osteoporosis, Zoledronic Acid
Eligibility Criteria
Inclusion Criteria: Patients who have received 3 infusions in the HORIZON-Pivotal Fracture (PFT) Study. Exclusion Criteria: Poor kidney, eye, or liver health Use of certain therapies for osteoporosis in the HORIZON-PFT study (other than the study medication) Abnormal calcium levels in the blood Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- Southern Arizona VA
- University of Arkansas for Medical Science
- Osteoporosis Medical Center
- Osteoporosis Prevention Center
- Diablo Clinical Research, Inc
- Colorado Center for Bone Research
- CRIA Research
- Radiant Research
- Comprehensive Clinical Trials, LLC
- United Osteoporosis Centers (UOC)
- Northwestern University Center for Clinical Research
- School of Medicine
- Medical Specialist Clinical Research Center
- Heartland Research Associates, LLC
- Maine Center for Osteoporosis Research and Education
- Osteoporosis Clinical Trial Center
- Clinical Pharmacology Study Groups
- Washington University Center for Clinical Studies
- New Mexico Clinical Research and Osteoporosis Center Inc
- Winthrop U Hospital
- Odyssey Research Services/CCRC Internal Medical
- University of Cincinnati Bone Health and Osteoporosis Center
- Thomas Jefferson University Hospital
- University of Pittsburgh
- Radiant Research
- Rhode Island Hospital, Endocrinology Clinical Research Unit
- University of Tennessee Health Science
- McGuire Veterans Affairs Medical Center
- VA Commonwealth University
- Puget Sound Osteoporosis Center
- Novartis
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Zoledronic Acid 6
Zoledronic Acid 3 Placebo 3
Placebo 3 Zoledronic Acid 3
Arm Description
Patients who received Zoledronic acid for 3 years in the core study (CZOL446H2301; NCT00049829) received a single intravenous infusion of 5 mg Zoledronic acid once a year for 3 years (at Months 36, 48 and 60) in this extension study for a total of 6 years of treatment.
Patients who were treated with Zoledronic acid for 3 years in the core study received a single intravenous matching Placebo infusion once a year for 3 years in this extension study.
Patients who were treated with placebo for 3 years in the core study received 5 mg Zoledronic acid in a single intravenous infusion once a year for 3 years (at Months 36, 48 and 60) in this extension study.
Outcomes
Primary Outcome Measures
Percentage Change in Bone Mineral Density (BMD) of Femoral Neck at Year 6 Relative to Year 3
The primary efficacy variable was the percentage change in BMD of the femoral neck as measured by dual x-ray absorptiometry (DXA) at Year 6 relative to Year 3. It was derived as 100 *(femoral neck BMD at Year 6 - femoral neck BMD at Year 3) / (femoral neck BMD at Year 3).
Secondary Outcome Measures
Bone Resorption and Formation Biochemical Markers at Year 4.5: P1NP
The amount of serum n-terminal propeptide of type I collagen (P1NP) as determined by the central laboratory.
Bone Resorption and Formation Biochemical Markers at Year 6: P1NP
The amount of serum P1NP as determined by the central laboratory
Percentage Change in BMD of Lumbar Spine at Year 4.5 Relative to Year 3
The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3).
Percentage Change in BMD of Lumbar Spine at Year 6 Relative to Year 3
The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3).
Percentage Change in BMD of Distal Radius at Year 4.5 Relative to Year 3
The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3).
Percentage Change in BMD of Distal Radius at Year 6 Relative to Year 3
The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3).
Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 4.5 Relative to Year 3
The percentage change in BMD as measured by DXA at 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3).
Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 6 Relative to Year 3
The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3).
Percentage of Patients With New and New/Worsening Morphometric Vertebral Fractures
Lateral vertebral x-rays were performed at the final core study visit and at Year 6 and read by a central expert reader at a central imaging laboratory to assess for new or new/worsening morphometric vertebral fracture. The percentage of patients with new morphometric vertebral fractures (observed for the first time) and patients with either new or worsening morphometric vertebral fractures was calculated.
Number of Participants With Incidence of Clinical Fracture
Clinical fracture excludes finger, toe, and facial bone fractures. Clinical vertebral fracture includes thoracic spine fracture and lumbar spine fracture. Non-vertebral fracture excludes clinical vertebral, finger, toe, and facial bone fractures.
Qualitative Bone Biopsy Parameters
Unpaired transiliac crest bone biopsy was performed for histomorphometry, which was obtained after double tetracycline labeling. No data were collected for Patients who received Placebo for the first 3 years of the study (Placebo 3 Zoledronic Acid 3).
Change in Serum Creatinine From Baseline to 9-11 Days Post Year 3 Infusion
Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after study drug infusion in Z6 patients compared to Z3P3 patients and in P3Z3 patients.
Change in Serum Creatinine From Baseline to 9-11 Days Post Year 4 Infusion
Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 4 study drug infusion.
Change in Serum Creatinine From Baseline to 9-11 Days Post Year 5 Infusion
Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 5 study drug infusion.
The Number of Participants With Clinically Significant Laboratory Parameters
Evaluate the laboratory key profile such as Calcium, Creatinine and Urea. The number of patients with clinically significant calcium, creatinine and urea were reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00145327
Brief Title
Double-blind Extension of HORIZON Pivotal Fracture Trial (Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis)
Official Title
A 3-year, Double-blind Extension to CZOL446H2301 to Evaluate the Long-term Safety and Efficacy of Zoledronic Acid in the Treatment of Osteoporosis in Postmenopausal Women Taking Calcium and Vitamin D
Study Type
Interventional
2. Study Status
Record Verification Date
June 2011
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
This extension study is designed to assess the long term safety and efficacy of zoledronic acid in postmenopausal women with osteoporosis who have participated in the CZOL446H2301 (NCT00049829): HORIZON Pivotal Fracture Trial. This extension study began after the 3-year core study ended. Baseline is the same as Year 3.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
Keywords
Osteoporosis, Zoledronic Acid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2456 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zoledronic Acid 6
Arm Type
Experimental
Arm Description
Patients who received Zoledronic acid for 3 years in the core study (CZOL446H2301; NCT00049829) received a single intravenous infusion of 5 mg Zoledronic acid once a year for 3 years (at Months 36, 48 and 60) in this extension study for a total of 6 years of treatment.
Arm Title
Zoledronic Acid 3 Placebo 3
Arm Type
Placebo Comparator
Arm Description
Patients who were treated with Zoledronic acid for 3 years in the core study received a single intravenous matching Placebo infusion once a year for 3 years in this extension study.
Arm Title
Placebo 3 Zoledronic Acid 3
Arm Type
Experimental
Arm Description
Patients who were treated with placebo for 3 years in the core study received 5 mg Zoledronic acid in a single intravenous infusion once a year for 3 years (at Months 36, 48 and 60) in this extension study.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid
Other Intervention Name(s)
Reclast, Aclasta
Intervention Description
Zoledronic Acid 5 mg in 100 mL physiologic 0.9% normal saline for intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Reclast, Aclasta
Intervention Description
100 mL physiologic 0.9% normal saline for intravenous infusion.
Primary Outcome Measure Information:
Title
Percentage Change in Bone Mineral Density (BMD) of Femoral Neck at Year 6 Relative to Year 3
Description
The primary efficacy variable was the percentage change in BMD of the femoral neck as measured by dual x-ray absorptiometry (DXA) at Year 6 relative to Year 3. It was derived as 100 *(femoral neck BMD at Year 6 - femoral neck BMD at Year 3) / (femoral neck BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72; end of extension study)
Secondary Outcome Measure Information:
Title
Bone Resorption and Formation Biochemical Markers at Year 4.5: P1NP
Description
The amount of serum n-terminal propeptide of type I collagen (P1NP) as determined by the central laboratory.
Time Frame
Year 4.5
Title
Bone Resorption and Formation Biochemical Markers at Year 6: P1NP
Description
The amount of serum P1NP as determined by the central laboratory
Time Frame
Year 6
Title
Percentage Change in BMD of Lumbar Spine at Year 4.5 Relative to Year 3
Description
The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)
Title
Percentage Change in BMD of Lumbar Spine at Year 6 Relative to Year 3
Description
The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6
Title
Percentage Change in BMD of Distal Radius at Year 4.5 Relative to Year 3
Description
The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)
Title
Percentage Change in BMD of Distal Radius at Year 6 Relative to Year 3
Description
The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72)
Title
Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 4.5 Relative to Year 3
Description
The percentage change in BMD as measured by DXA at 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)
Title
Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 6 Relative to Year 3
Description
The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3).
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72)
Title
Percentage of Patients With New and New/Worsening Morphometric Vertebral Fractures
Description
Lateral vertebral x-rays were performed at the final core study visit and at Year 6 and read by a central expert reader at a central imaging laboratory to assess for new or new/worsening morphometric vertebral fracture. The percentage of patients with new morphometric vertebral fractures (observed for the first time) and patients with either new or worsening morphometric vertebral fractures was calculated.
Time Frame
Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6
Title
Number of Participants With Incidence of Clinical Fracture
Description
Clinical fracture excludes finger, toe, and facial bone fractures. Clinical vertebral fracture includes thoracic spine fracture and lumbar spine fracture. Non-vertebral fracture excludes clinical vertebral, finger, toe, and facial bone fractures.
Time Frame
Extension Baseline (Year 3; Month 36) to Year 6
Title
Qualitative Bone Biopsy Parameters
Description
Unpaired transiliac crest bone biopsy was performed for histomorphometry, which was obtained after double tetracycline labeling. No data were collected for Patients who received Placebo for the first 3 years of the study (Placebo 3 Zoledronic Acid 3).
Time Frame
End of Study Visit at Year 6
Title
Change in Serum Creatinine From Baseline to 9-11 Days Post Year 3 Infusion
Description
Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after study drug infusion in Z6 patients compared to Z3P3 patients and in P3Z3 patients.
Time Frame
Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 3 infusion
Title
Change in Serum Creatinine From Baseline to 9-11 Days Post Year 4 Infusion
Description
Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 4 study drug infusion.
Time Frame
Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 4 infusion
Title
Change in Serum Creatinine From Baseline to 9-11 Days Post Year 5 Infusion
Description
Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 5 study drug infusion.
Time Frame
Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 5 infusion
Title
The Number of Participants With Clinically Significant Laboratory Parameters
Description
Evaluate the laboratory key profile such as Calcium, Creatinine and Urea. The number of patients with clinically significant calcium, creatinine and urea were reported.
Time Frame
Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to Year 6
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
68 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who have received 3 infusions in the HORIZON-Pivotal Fracture (PFT) Study.
Exclusion Criteria:
Poor kidney, eye, or liver health
Use of certain therapies for osteoporosis in the HORIZON-PFT study (other than the study medication)
Abnormal calcium levels in the blood
Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Chair
Facility Information:
Facility Name
Southern Arizona VA
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85723
Country
United States
Facility Name
University of Arkansas for Medical Science
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Osteoporosis Medical Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Osteoporosis Prevention Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Diablo Clinical Research, Inc
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Colorado Center for Bone Research
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80227
Country
United States
Facility Name
CRIA Research
City
Ft. Lauderdale
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
Facility Name
Radiant Research
City
Stuart
State/Province
Florida
ZIP/Postal Code
34996
Country
United States
Facility Name
Comprehensive Clinical Trials, LLC
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33409
Country
United States
Facility Name
United Osteoporosis Centers (UOC)
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Northwestern University Center for Clinical Research
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Medical Specialist Clinical Research Center
City
Munster
State/Province
Indiana
ZIP/Postal Code
46321
Country
United States
Facility Name
Heartland Research Associates, LLC
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67207
Country
United States
Facility Name
Maine Center for Osteoporosis Research and Education
City
Bangor
State/Province
Maine
ZIP/Postal Code
04401
Country
United States
Facility Name
Osteoporosis Clinical Trial Center
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Clinical Pharmacology Study Groups
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01610
Country
United States
Facility Name
Washington University Center for Clinical Studies
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
62110
Country
United States
Facility Name
New Mexico Clinical Research and Osteoporosis Center Inc
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Winthrop U Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Odyssey Research Services/CCRC Internal Medical
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58104
Country
United States
Facility Name
University of Cincinnati Bone Health and Osteoporosis Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19131
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
Radiant Research
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Rhode Island Hospital, Endocrinology Clinical Research Unit
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
University of Tennessee Health Science
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
McGuire Veterans Affairs Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
VA Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Puget Sound Osteoporosis Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98144
Country
United States
Facility Name
Novartis
City
Nuernberg
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
25214069
Citation
Eastell R, Boonen S, Cosman F, Reid IR, Palermo L, Cummings SR, Black DM. Relationship between pretreatment rate of bone loss and bone density response to once-yearly ZOL: HORIZON-PFT extension study. J Bone Miner Res. 2015 Mar;30(3):570-4. doi: 10.1002/jbmr.2361.
Results Reference
derived
PubMed Identifier
22161728
Citation
Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RL, Tan M, Ruzycky ME, Su G, Eastell R. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012 Feb;27(2):243-54. doi: 10.1002/jbmr.1494. Erratum In: J Bone Miner Res. 2012 Dec;27(12):2612.
Results Reference
derived
Learn more about this trial
Double-blind Extension of HORIZON Pivotal Fracture Trial (Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis)
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