Double-blind Extension of HORIZON Pivotal Fracture Trial (Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis)

Phase 3

Completed

Conditions: Osteoporosis

Interventions: Drug: Placebo
Drug: Zoledronic Acid

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

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.

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): Southern Arizona VA
🇺🇸
Tucson, Arizona, United States
University of Arkansas for Medical Science
🇺🇸
Little Rock, Arkansas, United States
Osteoporosis Medical Center
🇺🇸
Beverly Hills, California, United States
Osteoporosis Prevention Center
🇺🇸
San Diego, California, United States
Diablo Clinical Research, Inc
🇺🇸
Walnut Creek, California, United States
Colorado Center for Bone Research
🇺🇸
Lakewood, Colorado, United States
CRIA Research
🇺🇸
Ft. Lauderdale, Florida, United States
Radiant Research
🇺🇸
Wyomissing, Pennsylvania, United States
Comprehensive Clinical Trials, LLC
🇺🇸
West Palm Beach, Florida, United States
United Osteoporosis Centers (UOC)
🇺🇸
Gainesville, Georgia, United States
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Southern Arizona VA
🇺🇸Tucson, Arizona, United States