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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00145327
• Other study ID #: CZOL446H2301E1
• Status: Completed
• Phase: Phase 3
• First received: September 1, 2005
• Last updated: June 24, 2011
• Start date: May 2005
• Est. completion date: November 2009

Study information

• Verified date: June 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2456
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 68 Years to 90 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

Drug:
• Zoledronic Acid
Zoledronic Acid 5 mg in 100 mL physiologic 0.9% normal saline for intravenous infusion.
• Placebo
100 mL physiologic 0.9% normal saline for intravenous infusion.

Locations

Country	Name	City	State
Germany	Novartis	Nuernberg
United States	New Mexico Clinical Research and Osteoporosis Center Inc	Albuquerque	New Mexico
United States	Maine Center for Osteoporosis Research and Education	Bangor	Maine
United States	Osteoporosis Medical Center	Beverly Hills	California
United States	Northwestern University Center for Clinical Research	Chicago	Illinois
United States	University of Cincinnati Bone Health and Osteoporosis Center	Cincinnati	Ohio
United States	Odyssey Research Services/CCRC Internal Medical	Fargo	North Dakota
United States	CRIA Research	Ft. Lauderdale	Florida
United States	United Osteoporosis Centers (UOC)	Gainesville	Georgia
United States	Osteoporosis Clinical Trial Center	Hagerstown	Maryland
United States	School of Medicine	Indianapolis	Indiana
United States	Colorado Center for Bone Research	Lakewood	Colorado
United States	University of Arkansas for Medical Science	Little Rock	Arkansas
United States	University of Tennessee Health Science	Memphis	Tennessee
United States	Winthrop U Hospital	Mineola	New York
United States	Medical Specialist Clinical Research Center	Munster	Indiana
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital, Endocrinology Clinical Research Unit	Providence	Rhode Island
United States	McGuire Veterans Affairs Medical Center	Richmond	Virginia
United States	VA Commonwealth University	Richmond	Virginia
United States	Osteoporosis Prevention Center	San Diego	California
United States	Puget Sound Osteoporosis Center	Seattle	Washington
United States	Washington University Center for Clinical Studies	St. Louis	Missouri
United States	Radiant Research	Stuart	Florida
United States	Southern Arizona VA	Tucson	Arizona
United States	Diablo Clinical Research, Inc	Walnut Creek	California
United States	Comprehensive Clinical Trials, LLC	West Palm Beach	Florida
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Clinical Pharmacology Study Groups	Worcester	Massachusetts
United States	Radiant Research	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72; end of extension study)	No
Secondary	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.	Year 4.5	No
Secondary	Bone Resorption and Formation Biochemical Markers at Year 6: P1NP	The amount of serum P1NP as determined by the central laboratory	Year 6	No
Secondary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)	No
Secondary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6	No
Secondary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)	No
Secondary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72)	No
Secondary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)	No
Secondary	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).	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72)	No
Secondary	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.	Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6	No
Secondary	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.	Extension Baseline (Year 3; Month 36) to Year 6	No
Secondary	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).	End of Study Visit at Year 6	Yes
Secondary	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.	Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 3 infusion	Yes
Secondary	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.	Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 4 infusion	No
Secondary	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.	Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 5 infusion	No
Secondary	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.	Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to Year 6	Yes