Double-blind Extension of HORIZON Pivotal Fracture Trial (Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis)
- Registration Number
- NCT00145327
- Lead Sponsor
- Novartis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 2456
- Patients who have received 3 infusions in the HORIZON-Pivotal Fracture (PFT) Study.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zoledronic Acid 3 Placebo 3 Placebo 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. Zoledronic Acid 6 Zoledronic Acid 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. Placebo 3 Zoledronic Acid 3 Zoledronic Acid 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.
- Primary Outcome Measures
Name Time Method Percentage Change in Bone Mineral Density (BMD) of Femoral Neck at Year 6 Relative to Year 3 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72; end of extension study) 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
Name Time Method Bone Resorption and Formation Biochemical Markers at Year 4.5: P1NP Year 4.5 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 Year 6 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72) 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72) 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 Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 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 Extension Baseline (Year 3; Month 36) to Year 6 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 End of Study Visit at Year 6 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 Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the 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 Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the 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 Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the 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 Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to Year 6 Evaluate the laboratory key profile such as Calcium, Creatinine and Urea. The number of patients with clinically significant calcium, creatinine and urea were reported.
Trial Locations
- Locations (30)
Comprehensive Clinical Trials, LLC
🇺🇸West Palm Beach, Florida, United States
Maine Center for Osteoporosis Research and Education
🇺🇸Bangor, Maine, United States
Washington University Center for Clinical Studies
🇺🇸St. Louis, Missouri, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Novartis
🇩🇪Nuernberg, Germany
Heartland Research Associates, LLC
🇺🇸Wichita, Kansas, United States
Odyssey Research Services/CCRC Internal Medical
🇺🇸Fargo, North Dakota, United States
Osteoporosis Prevention Center
🇺🇸San Diego, California, United States
School of Medicine
🇺🇸Indianapolis, Indiana, United States
Puget Sound Osteoporosis Center
🇺🇸Seattle, Washington, United States
Southern Arizona VA
🇺🇸Tucson, Arizona, United States
Osteoporosis Medical Center
🇺🇸Beverly Hills, California, United States
University of Arkansas for Medical Science
🇺🇸Little Rock, Arkansas, United States
Diablo Clinical Research, Inc
🇺🇸Walnut Creek, California, United States
Colorado Center for Bone Research
🇺🇸Lakewood, Colorado, United States
Medical Specialist Clinical Research Center
🇺🇸Munster, Indiana, United States
CRIA Research
🇺🇸Ft. Lauderdale, Florida, United States
Northwestern University Center for Clinical Research
🇺🇸Chicago, Illinois, United States
United Osteoporosis Centers (UOC)
🇺🇸Gainesville, Georgia, United States
Clinical Pharmacology Study Groups
🇺🇸Worcester, Massachusetts, United States
Osteoporosis Clinical Trial Center
🇺🇸Hagerstown, Maryland, United States
University of Cincinnati Bone Health and Osteoporosis Center
🇺🇸Cincinnati, Ohio, United States
New Mexico Clinical Research and Osteoporosis Center Inc
🇺🇸Albuquerque, New Mexico, United States
Rhode Island Hospital, Endocrinology Clinical Research Unit
🇺🇸Providence, Rhode Island, United States
Winthrop U Hospital
🇺🇸Mineola, New York, United States
McGuire Veterans Affairs Medical Center
🇺🇸Richmond, Virginia, United States
University of Tennessee Health Science
🇺🇸Memphis, Tennessee, United States
VA Commonwealth University
🇺🇸Richmond, Virginia, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Radiant Research
🇺🇸Wyomissing, Pennsylvania, United States