Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density

A Multi-center, Randomized, Double-blind, Double-dummy Study in Postmenopausal Women With Low Bone Mineral Density to Compare the Effects of a Single Dose of i.v. Zoledronic Acid 5 mg, With Daily Oral Raloxifene 60 mg OD on Bone Turnover Markers

This study will compare the effects of Zoledronic acid and Raloxifene in reducing bone turnover markers in postmenopausal women with low bone mineral density over 6 months.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: Drug: Zoledronic acid; Drug: Raloxifene; Drug: Placebo oral pills; Drug: Placebo intravenous (i.v.) infusion

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Women's Health Research
  • California
    • Buena Park, California, United States, 90620
      • Associated Pharma Research Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Women's Physicians of Jacksonville
    • Tampa, Florida, United States, 33624
      • Tampa Clinical Research
  • Illinois
    • Springfield, Illinois, United States, 62703
      • Springfield Clinic
  • Missouri
    • St Louis, Missouri, United States, 63131
      • Consultants in Women's Health Care
  • Nebraska
    • Omaha, Nebraska, United States, 68152
      • Alegent Health
  • Nevada
    • Pahrump, Nevada, United States, 89048
      • Specialty Medical and Research Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • UMDNJ-Robert Wood Johnson Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Kernodle Clinic, Inc.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97205
      • The Portland Clinic
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Institute for Clinical Research
  • Washington
    • Renton, Washington, United States, 98055
      • Valley Women's Health Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Females, between 45 and 80 years (inclusive) of age, considered post-menopausal according to one of the following guidelines:
• Cessation of menses for 18 months in women < 50 years of age
• Cessation of menses for 12 months in women age 50 years or over
• Documented bilateral oophorectomy at least 1 year previously
• Documented T score of less than or equal to -1.5 on dual energy X-ray absorptiometry (DXA) scan at the lumbar spine, total hip or femoral neck within 24 months prior to screening, and clinically indicated for treatment with bisphosphonates (BPs) for osteopenia or osteoporosis
• Signed informed consent prior to initiation of any study procedure

Exclusion Criteria:

• Prior treatment with i.v. bisphosphonates within the last 2 years
• Previous use of oral bisphosphonates within the past 2 years (unless used for less than 8 weeks*).
• *NOTE: If used less than 8 weeks, the washout period is 6 months.
• Treatment with raloxifene, calcitonin, tibolone or hormone replacement therapy. The washout period for these medications is 6 months prior to randomization.
• Any treatment with strontium renalate, sodium fluoride or parathyroid hormone
• Use of systemic high dose corticosteroids at an average dose of ≥ 7.5 mg per day of oral prednisone or equivalent for a period of three months or more within the previous year
• Treatment with any investigational drug within 30 days prior to randomization
• Any woman of child bearing potential
• Patients with fractures occurring within three months prior to randomization
• History of hypersensitivity to bisphosphonates
• History of non-traumatic uveitis or iritis, within 2 years prior to study entry.
• A history of invasive malignancy of any organ system, treated or untreated, within the past 12 months prior to screening; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed.
• Previous major solid organ transplant recipient or on a transplant waiting list
• History of hyperparathyroidism, hypoparathyroidism, Osteogenesis imperfecta, Paget's disease or any metabolic bone disease other than osteoporosis
• Any medical condition which would interfere with the action of the study drug or limit life expectancy to less than 6 months
• Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial
• Active dental infection, unhealed dental extraction or planned oral surgery within 3 month prior to randomization.
• Calculated creatinine clearance < 30 mL/min
• Greater than 2+ protein on urine dipstick without evidence of contamination or bacteriuria (may be repeated one time, at least a day apart).
• Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.08 mmol/L (8.3 mg/dL) at screening
• AST, ALT or serum alkaline phosphatase greater than twice the upper limit of normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zoledronic Acid; Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group)	Drug: Zoledronic acid; Other Names: Reclast, Aclasta; Drug: Placebo oral pills
Active Comparator: Raloxifene; Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group)	Drug: Raloxifene; Drug: Placebo intravenous (i.v.) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.)	The primary efficacy variable was the change from baseline in urine NTx (corrected by creatinine). The primary analysis time point was at 6 months of treatment. The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urine NTx at 2 Months	The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.	Baseline and 2 months
Change From Baseline in Urine NTx at 4 Months	The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine.	Baseline and 4 months
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months		Baseline and 2 months
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months		Baseline and 4 months
Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months		Baseline and 6 months
Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire	The investigator was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."	Immediately after infusion procedure
Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire	The study coordinator (nurse) was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."	Immediately after infusion procedure
Overall Patient Satisfaction Assessed by Satisfaction Questionnaire	Patients were asked to complete the satisfaction questionnaire at baseline. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: "not at all," "a little," "somewhat," "quite," or "completely."	Immediately after infusion procedure
Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens	At the end-of-study visit, Month 6, patients were asked to complete a questionnaire to assess preference for the different treatment modalities (annual i.v. infusion vs. daily oral capsule). The possible answers to question were: "once a year i.v. infusion," "once daily pill," or "both are equal."	At 6 month visit

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Bachmann G, Kriegman A, Goncalves J, Kianifard F, Warren M, Simon JA. Effect of zoledronic acid compared with raloxifene on bone turnover markers in postmenopausal women with low bone density. Menopause. 2011 Aug;18(8):851-6. doi: 10.1097/gme.0b013e31820b80f1.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: February 1, 2007
• First Submitted That Met QC Criteria: February 2, 2007
• First Posted (Estimate): February 5, 2007

Study Record Updates

• Last Update Posted (Estimate): March 29, 2011
• Last Update Submitted That Met QC Criteria: March 25, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Post-menopausal; Osteoporosis; Bone mineral density
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Raloxifene Hydrochloride; Zoledronic Acid
• Other Study ID Numbers: CZOL446HUS121