Safety/Efficacy of Zoledronic Acid and Alendronate on Bone Metabolism in Postmenopausal Women With Osteoporosis (ROSE)

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00404820
First received: November 28, 2006
Last updated: June 6, 2011
Last verified: June 2011
  Purpose

The aim of this study was to examine the effect of zoledronic acid and alendronate on bone metabolism as measured by biomarkers in postmenopausal women with osteoporosis.


Condition Intervention Phase
Osteoporosis
Drug: Zoledronic acid 5 mg solution
Drug: Alendronate 70 mg tablets
Drug: Calcium/Vitamin D
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Open-label, Controlled, One-year Trial to Measure the Effect of Zoledronic Acid and Alendronate on Bone Metabolism in Postmenopausal Women With Osteopenia and Osteoporosis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Intent-to-Treat Population [ Time Frame: Screening to end of study (Month 12) ] [ Designated as safety issue: No ]
    The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.

  • Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Per Protocol Population [ Time Frame: Screening to end of study (Month 12) ] [ Designated as safety issue: No ]
    The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.


Secondary Outcome Measures:
  • Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 [ Time Frame: Screening to end of study (Month 12) ] [ Designated as safety issue: No ]
    The level of bone activity as measured by P1NP over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.

  • Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12 [ Time Frame: Baseline to end of study (Month 12) ] [ Designated as safety issue: No ]
    The Qualeffo-41 QoL questionnaire was completed by the patient at Baseline and at Month 12. The questionnaire includes 41 questions covering 7 domains (pain, physical function and activities of daily living, physical function and jobs around the house, physical function and mobility, leisure and social activities, general health perception, mental function). Scores on each question range from 1 to 3, 4, or 5. The total score summed over all questions ranges from 41-205 points; the lower the score the higher the quality of life. A negative change score indicates improvement.

  • Number of Patients With a Clinical Fracture From Baseline to Month 12 [ Time Frame: Baseline to end of study (Month 12) ] [ Designated as safety issue: No ]
    A diagnosis of clinical fracture was based on physical examination findings, ie, swelling, tenderness, limited movement, pain.

  • Change in Body Height From Baseline to Month 12 [ Time Frame: Baseline to end of study (Month 12) ] [ Designated as safety issue: No ]
    Body height was measured at Baseline and at the end of the study (Month 12) and the change in height calculated.

  • Therapy Preference at End of Study (Month 12) [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Patients were administered a questionnaire at the end of the study in which they were asked which type of therapy, weekly oral or yearly iv, they preferred.


Enrollment: 604
Study Start Date: October 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic acid 5 mg
Patients received zoledronic acid 5 mg in 100 ml solution in a 15 minute intravenous (iv) infusion once per year. The peripheral iv infusion was preceded by and followed by a 10 ml normal saline flush of the intravenous line. In addition to study therapy, all participants received 1200 mg elemental calcium and 800 IU of vitamin D daily. Calcium and vitamin D were supplied in a chewable tablet that was to be taken twice daily.
Drug: Zoledronic acid 5 mg solution
Zoledronic acid was supplied as a concentrate of 5.33 mg zoledronic acid monohydrate in a 100 ml solution. 5.33 mg zoledronic acid monohydrate equals 5 mg zoledronic acid.
Drug: Calcium/Vitamin D
Combined elemental calcium / vitamin D chewable tablets. Participants took 2 tablets a day, for a daily dose of calcium 1200 mg/vitamin D 800 IU.
Active Comparator: Alendronate 70 mg
Patients received an alendronate 70 mg tablet once weekly with 200 ml of tap water in the morning on an empty stomach at least 30 minutes before the first meal. Patients were to remain in an upright position for 30 minutes after swallowing the tablet. In addition to study therapy, all participants received 1200 mg elemental calcium and 800 IU of vitamin D daily. Calcium and vitamin D were supplied in a chewable tablet that was to be taken twice daily.
Drug: Alendronate 70 mg tablets
Patients received an alendronate 70 mg tablet once weekly with 200 ml of tap water in the morning on an empty stomach at least 30 minutes before the first meal.
Drug: Calcium/Vitamin D
Combined elemental calcium / vitamin D chewable tablets. Participants took 2 tablets a day, for a daily dose of calcium 1200 mg/vitamin D 800 IU.

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Low bone mineral density (as indicated by a "t-score" of -2.0 or lower) postmenopausal women

Exclusion Criteria:

- Previous use of oral and iv bisphosphonates, parathormone, strontium ranelate, sodium fluoride.

Other protocol-defined inclusion/exclusion criteria applied to the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00404820

Locations
Germany
For site information contact Novartis Pharmaceuticals
Multiple Cities, Germany
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharma GmbH, Germany +49 911 273-0 Novartis
  More Information

No publications provided

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00404820     History of Changes
Other Study ID Numbers: CZOL446HDE31
Study First Received: November 28, 2006
Results First Received: January 5, 2011
Last Updated: June 6, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
osteoporosis
bisphosphonate
biomarker
zoledronic acid
alendronate
postmenopausal

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Alendronate
Calcium, Dietary
Diphosphonates
Ergocalciferols
Pharmaceutical Solutions
Vitamin D
Vitamins
Zoledronic acid
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014