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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00145327
First received: September 1, 2005
Last updated: June 24, 2011
Last verified: June 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Osteoporosis
 Drug: Zoledronic Acid
Drug: Placebo
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage Change in Bone Mineral Density (BMD) of Femoral Neck at Year 6 Relative to 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 4.5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Extension Baseline (Year 3; Month 36) to Year 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of Study Visit at Year 6 ] [ Designated as safety issue: Yes ]
    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 [ 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 ] [ Designated as safety issue: Yes ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to Year 6 ] [ Designated as safety issue: Yes ]
    Evaluate the laboratory key profile such as Calcium, Creatinine and Urea. The number of patients with clinically significant calcium, creatinine and urea were reported.


Enrollment: 2456
Study Start Date: May 2005
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic Acid 6
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.
 Drug: Zoledronic Acid
Zoledronic Acid 5 mg in 100 mL physiologic 0.9% normal saline for intravenous infusion.
Other Name: Reclast, Aclasta
Placebo Comparator: Zoledronic Acid 3 Placebo 3
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.
 Drug: Placebo
100 mL physiologic 0.9% normal saline for intravenous infusion.
Other Name: Reclast, Aclasta
Experimental: Placebo 3 Zoledronic Acid 3
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.
 Drug: Zoledronic Acid
Zoledronic Acid 5 mg in 100 mL physiologic 0.9% normal saline for intravenous infusion.
Other Name: Reclast, Aclasta

  Eligibility

Ages Eligible for Study:   68 Years to 90 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00145327

  Show 31 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharmaceuticals Sponsor GmbH
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00145327     History of Changes
Other Study ID Numbers: CZOL446H2301E1
Study First Received: September 1, 2005
Results First Received: January 21, 2011
Last Updated: June 24, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Osteoporosis, Zoledronic Acid

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
 Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013