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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Zoledronic acid 5 mg solution; Drug: Calcium/Vitamin D; Drug: Alendronate 70 mg tablets

• Study Type: Interventional
• Enrollment (Actual): 604
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Multiple Cities, Germany
    • For site information contact Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Screening to end of study (Month 12)
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	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.	Screening to end of study (Month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12	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.	Screening to end of study (Month 12)
Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12	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.	Baseline to end of study (Month 12)
Number of Patients With a Clinical Fracture From Baseline to Month 12	A diagnosis of clinical fracture was based on physical examination findings, ie, swelling, tenderness, limited movement, pain.	Baseline to end of study (Month 12)
Change in Body Height From Baseline to Month 12	Body height was measured at Baseline and at the end of the study (Month 12) and the change in height calculated.	Baseline to end of study (Month 12)
Therapy Preference at End of Study (Month 12)	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.	Month 12

Collaborators and Investigators

• Sponsor: Novartis
• Investigators: Study Director: Novartis Pharma GmbH, Germany +49 911 273-0, Novartis

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: November 28, 2006
• First Submitted That Met QC Criteria: November 28, 2006
• First Posted (Estimate): November 29, 2006

Study Record Updates

• Last Update Posted (Estimate): July 1, 2011
• Last Update Submitted That Met QC Criteria: June 6, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: biomarker; osteoporosis; postmenopausal; bisphosphonate; zoledronic acid; alendronate
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Alendronate; Zoledronic Acid
• Other Study ID Numbers: CZOL446HDE31